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J Biomol Struct Dyn

Designing a multi-epitope vaccine against SARS-CoV-2: an immunoinformatics approach.

Ongoing COVID-19 outbreak has raised a drastic challenge to global public health security. Most of the patients with COVID-19 suffer from mild flu-like illnesses such as cold and fever; however, few percentages of the patients progress from severe illness to death, mostly in an immunocompromised individual. The causative agent of COVID-19 is an RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite these debilitating conditions, no medication to stop the disease progression or vaccination is available till now. Therefore, we aimed to formulate a multi-epitope vaccine against SARS-CoV-2 by utilizing an immunoinformatics approach. For this purpose, we used the SARS-CoV-2 spike glycoprotein to determine the immunodominant T- and B-cell epitopes. After rigorous assessment, we designed a vaccine construct using four potential epitopes from each of the three epitope classes such as cytotoxic T-lymphocytes, helper T-lymphocyte, and linear B-lymphocyte epitopes. The designed vaccine was antigenic, immunogenic, and non-allergenic with suitable physicochemical properties and has higher solubility. More importantly, the predicted vaccine structure was similar to the native protein. Further investigations indicated a strong and stable binding interaction between the vaccine and the toll-like receptor (TLR4). Strong binding stability and structural compactness were also evident in molecular dynamics simulation. Furthermore, the computer-generated immune simulation showed that the vaccine could trigger real-life-like immune responses upon administration into humans. Finally, codon optimization based on Escherichia coli K12 resulted in optimal GC content and higher CAI value followed by incorporating it into the cloning vector pET28+(a). Overall, these results suggest that the designed peptide vaccine can serve as an excellent prophylactic candidate against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.

covid-19;sars-cov-2;dynamics simulation;immune simulation;immunoinformatics;multi-epitope vaccine

Journal Article

Samad, Abdus;Ahammad, Foysal;Nain, Zulkar;Alam, Rahat;Imon, Raihan Rahman;Hasan, Mahadi;Rahman, Md Shahedur

10.1080/07391102.2020.1792347

[Title]: Designing a multi-epitope vaccine against SARS-CoV-2: an immunoinformatics approach. [Abstract]: Ongoing COVID-19 outbreak has raised a drastic challenge to global public health security. Most of the patients with COVID-19 suffer from mild flu-like illnesses such as cold and fever; however, few percentages of the patients progress from severe illness to death, mostly in an immunocompromised individual. The causative agent of COVID-19 is an RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite these debilitating conditions, no medication to stop the disease progression or vaccination is available till now. Therefore, we aimed to formulate a multi-epitope vaccine against SARS-CoV-2 by utilizing an immunoinformatics approach. For this purpose, we used the SARS-CoV-2 spike glycoprotein to determine the immunodominant T- and B-cell epitopes. After rigorous assessment, we designed a vaccine construct using four potential epitopes from each of the three epitope classes such as cytotoxic T-lymphocytes, helper T-lymphocyte, and linear B-lymphocyte epitopes. The designed vaccine was antigenic, immunogenic, and non-allergenic with suitable physicochemical properties and has higher solubility. More importantly, the predicted vaccine structure was similar to the native protein. Further investigations indicated a strong and stable binding interaction between the vaccine and the toll-like receptor (TLR4). Strong binding stability and structural compactness were also evident in molecular dynamics simulation. Furthermore, the computer-generated immune simulation showed that the vaccine could trigger real-life-like immune responses upon administration into humans. Finally, codon optimization based on Escherichia coli K12 resulted in optimal GC content and higher CAI value followed by incorporating it into the cloning vector pET28+(a). Overall, these results suggest that the designed peptide vaccine can serve as an excellent prophylactic candidate against SARS-CoV-2. Communicated by Ramaswamy H. Sarma. [Keywords]: covid-19;sars-cov-2;dynamics simulation;immune simulation;immunoinformatics;multi-epitope vaccine

Br J Pharmacol

Repositioning PARP inhibitors for SARS-CoV-2 infection(COVID-19); a new multi-pronged therapy for acute respiratory distress syndrome?

Clinically approved PARP inhibitors (PARPi) have a mild adverse effect profile and are well tolerated as continuous daily oral therapy. We review the evidence that justifies the repurposing of PARPi to block the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and combat the life-threatening sequelae of coronavirus disease 2019 (COVID-19) by several mechanisms. PARPi can effectively decrease IL-6, IL-1 and TNF-alpha levels (key interleukins in SARS-CoV-2-induced cytokine storm) and can alleviate subsequent lung fibrosis, as demonstrated in murine experiments and clinical trials. PARPi can tune macrophages towards a tolerogenic phenotype. PARPi may also counteract SARS-CoV-2-induced and inflammation-induced cell death and support cell survival. PARPi is effective in animal models of acute respiratory distress syndrome (ARDS), asthma and ventilator-induced lung injury. PARPi may potentiate the effectiveness of tocilizumab, anakinra, sarilumab, adalimumab, canakinumab or siltuximab therapy. The evidence suggests that PARPi would benefit COVID-19 patients and trials should be undertaken.

Journal Article;Research Support, Non-U.S. Gov't;Review

Curtin, Nicola;Banyai, Krisztian;Thaventhiran, James;Le Quesne, John;Helyes, Zsuzsanna;Bai, Peter

10.1111/bph.15137

[Title]: Repositioning PARP inhibitors for SARS-CoV-2 infection(COVID-19); a new multi-pronged therapy for acute respiratory distress syndrome? [Abstract]: Clinically approved PARP inhibitors (PARPi) have a mild adverse effect profile and are well tolerated as continuous daily oral therapy. We review the evidence that justifies the repurposing of PARPi to block the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and combat the life-threatening sequelae of coronavirus disease 2019 (COVID-19) by several mechanisms. PARPi can effectively decrease IL-6, IL-1 and TNF-alpha levels (key interleukins in SARS-CoV-2-induced cytokine storm) and can alleviate subsequent lung fibrosis, as demonstrated in murine experiments and clinical trials. PARPi can tune macrophages towards a tolerogenic phenotype. PARPi may also counteract SARS-CoV-2-induced and inflammation-induced cell death and support cell survival. PARPi is effective in animal models of acute respiratory distress syndrome (ARDS), asthma and ventilator-induced lung injury. PARPi may potentiate the effectiveness of tocilizumab, anakinra, sarilumab, adalimumab, canakinumab or siltuximab therapy. The evidence suggests that PARPi would benefit COVID-19 patients and trials should be undertaken. [Keywords]:

Gerontology

The Crucial Role of Nurses and Social Workers in Initiating End-of-Life Communication to Reduce Overtreatment in the Midst of the COVID-19 Pandemic.

The large scale and rapid spread of the current COVID-19 pandemic has changed the way hospitals and other health services operate. Opportunities for patient-centered decision-making at the end of life are being jeopardized by a scarcity of health system resources. In response, the traditional doctor-initiated advanced care planning (ACP) for critical illness may also need to be readjusted. We propose nurse-led and allied health-led ACP discussions to ensure patient and family inclusion and understanding of the disease prognosis, prevention of overtreatment, and potential outcomes in crisis times. We highlight known barriers and list enablers, long-term and short-term opportunities to assist in the culture change.

advanced care planning;allied health;covid-19;end of life;nurses

Journal Article

Raftery, Chris;Lewis, Ebony;Cardona, Magnolia

10.1159/000509103

[Title]: The Crucial Role of Nurses and Social Workers in Initiating End-of-Life Communication to Reduce Overtreatment in the Midst of the COVID-19 Pandemic. [Abstract]: The large scale and rapid spread of the current COVID-19 pandemic has changed the way hospitals and other health services operate. Opportunities for patient-centered decision-making at the end of life are being jeopardized by a scarcity of health system resources. In response, the traditional doctor-initiated advanced care planning (ACP) for critical illness may also need to be readjusted. We propose nurse-led and allied health-led ACP discussions to ensure patient and family inclusion and understanding of the disease prognosis, prevention of overtreatment, and potential outcomes in crisis times. We highlight known barriers and list enablers, long-term and short-term opportunities to assist in the culture change. [Keywords]: advanced care planning;allied health;covid-19;end of life;nurses

J Pediatr Surg Case Rep

Intestinal ischemia secondary to Covid-19.

With the wide spread of the current SARS-Cov (Covid-19), It was found that about 2% of children was affected according to several studies, it should be mentioned that Those children are most often asymptomatic, but the current concern is about a vascular inflammatory disease which is similar to Kawasaki disease observed in children with Covid-19. we report a case of a 9-year-old girl, known to have idiopathic medullar aplasia, admitted to the emergency department for a pseudo appendicular syndrome with shock, neurological abnormalities and skin lesions. She underwent an emergency surgery; the peroperative exploration suggested an ischemic bowel lesion of the ileal loop and a healthy appendix. The link involving a Covid-19 infection was well established (RT-PCR +). We shared in common our clinical, radiological, biological and pathological data to draw attention towards the intestinal vasculitis that can be a part in the MIS-C related to Covid 19. To our best knowledge, this is the first case encountered of combination between Covid-19 with intestinal ischemic in children.

intestinal ischemia;kawasaki like;medullar aplasia;sars-cov 2

Case Reports

Khesrani, Lamia Sabrina;Chana, Karima;Sadar, Fatma Zohra;Dahdouh, Abdelkader;Ladjadj, Yasmina;Bouguermouh, Dania

10.1016/j.epsc.2020.101604

[Title]: Intestinal ischemia secondary to Covid-19. [Abstract]: With the wide spread of the current SARS-Cov (Covid-19), It was found that about 2% of children was affected according to several studies, it should be mentioned that Those children are most often asymptomatic, but the current concern is about a vascular inflammatory disease which is similar to Kawasaki disease observed in children with Covid-19. we report a case of a 9-year-old girl, known to have idiopathic medullar aplasia, admitted to the emergency department for a pseudo appendicular syndrome with shock, neurological abnormalities and skin lesions. She underwent an emergency surgery; the peroperative exploration suggested an ischemic bowel lesion of the ileal loop and a healthy appendix. The link involving a Covid-19 infection was well established (RT-PCR +). We shared in common our clinical, radiological, biological and pathological data to draw attention towards the intestinal vasculitis that can be a part in the MIS-C related to Covid 19. To our best knowledge, this is the first case encountered of combination between Covid-19 with intestinal ischemic in children. [Keywords]: intestinal ischemia;kawasaki like;medullar aplasia;sars-cov 2

J Alzheimers Dis

Antivirals Against SARS-CoV2: Relevance to the Treatment of Alzheimer's Disease.

A recent study in vitro has shown that a sulphated polysaccharide, a type of fucoidan, has potent antiviral activity against SARS-Cov2. If the antiviral action were successful also for COVID-19 patients, it would be enormously valuable against not only acute disease but also long-term mental effects, which might include Alzheimer's disease (AD). In a trial of AD patients, the apparent success of treatment with a polysaccharide, GV971, was suggested to result from antiviral action against herpes simplex virus type 1 (HSV1) in brain, a pathogen strongly implicated in AD, and that sulphation of GV971, making it fucoidan-like, might increase its putative antiviral action. These data indicate that treatment of AD patients might be very effective using valacyclovir, a conventional antiviral, which inhibits viral replication, together with a fucoidan, which blocks virus entry into cells.

alzheimer's disease;covid-19;herpes simplex virus type 1;sars-cov2;antiviral;fucoidans

Journal Article;Comment

Itzhaki, Ruth F

10.3233/JAD-200986

[Title]: Antivirals Against SARS-CoV2: Relevance to the Treatment of Alzheimer's Disease. [Abstract]: A recent study in vitro has shown that a sulphated polysaccharide, a type of fucoidan, has potent antiviral activity against SARS-Cov2. If the antiviral action were successful also for COVID-19 patients, it would be enormously valuable against not only acute disease but also long-term mental effects, which might include Alzheimer's disease (AD). In a trial of AD patients, the apparent success of treatment with a polysaccharide, GV971, was suggested to result from antiviral action against herpes simplex virus type 1 (HSV1) in brain, a pathogen strongly implicated in AD, and that sulphation of GV971, making it fucoidan-like, might increase its putative antiviral action. These data indicate that treatment of AD patients might be very effective using valacyclovir, a conventional antiviral, which inhibits viral replication, together with a fucoidan, which blocks virus entry into cells. [Keywords]: alzheimer's disease;covid-19;herpes simplex virus type 1;sars-cov2;antiviral;fucoidans

J Public Econ

Polarization and public health: Partisan differences in social distancing during the coronavirus pandemic.

We study partisan differences in Americans' response to the COVID-19 pandemic. Political leaders and media outlets on the right and left have sent divergent messages about the severity of the crisis, which could impact the extent to which Republicans and Democrats engage in social distancing and other efforts to reduce disease transmission. We develop a simple model of a pandemic response with heterogeneous agents that clarifies the causes and consequences of heterogeneous responses. We use location data from a large sample of smartphones to show that areas with more Republicans engaged in less social distancing, controlling for other factors including public policies, population density, and local COVID cases and deaths. We then present new survey evidence of significant gaps at the individual level between Republicans and Democrats in self-reported social distancing, beliefs about personal COVID risk, and beliefs about the future severity of the pandemic.

coronavirus;health behaviors;media trust;political polarization

Journal Article

Allcott, Hunt;Boxell, Levi;Conway, Jacob;Gentzkow, Matthew;Thaler, Michael;Yang, David

10.1016/j.jpubeco.2020.104254

[Title]: Polarization and public health: Partisan differences in social distancing during the coronavirus pandemic. [Abstract]: We study partisan differences in Americans' response to the COVID-19 pandemic. Political leaders and media outlets on the right and left have sent divergent messages about the severity of the crisis, which could impact the extent to which Republicans and Democrats engage in social distancing and other efforts to reduce disease transmission. We develop a simple model of a pandemic response with heterogeneous agents that clarifies the causes and consequences of heterogeneous responses. We use location data from a large sample of smartphones to show that areas with more Republicans engaged in less social distancing, controlling for other factors including public policies, population density, and local COVID cases and deaths. We then present new survey evidence of significant gaps at the individual level between Republicans and Democrats in self-reported social distancing, beliefs about personal COVID risk, and beliefs about the future severity of the pandemic. [Keywords]: coronavirus;health behaviors;media trust;political polarization

Int J Health Policy Manag

COVID-19 Intervention Scenarios for a Long-term Disease Management.

BACKGROUND: The first outbreak of coronavirus disease 2019 (COVID-19) was successfully restrained in many countries around the world by means of a severe lockdown. Now, we are entering the second phase of the pandemics in which the spread of the virus needs to be contained within the limits that national health systems can cope with. This second phase of the epidemics is expected to last until a vaccination is available or herd immunity is reached. Long-term management strategies thus need to be developed. METHODS: In this paper we present a new agent-based simulation model "COVID-19 ABM" with which we simulate 4 alternative scenarios for the second "new normality" phase that can help decision-makers to take adequate control and intervention measures. RESULTS: The scenarios resulted in distinctly different outcomes. A continued lockdown could regionally eradicate the virus within a few months, whereas a relaxation back to 80% of former activity-levels was followed by a second outbreak. Contact-tracing as well as adaptive response strategies could keep COVID-19 within limits. CONCLUSION: The main insights are that low-level voluntary use of tracing apps shows no relevant effects on containing the virus, whereas medium or high-level tracing allows maintaining a considerably higher level of social activity. Adaptive control strategies help in finding the level of least restrictions. A regional approach to adaptive management can further help in fine-tuning the response to regional dynamics and thus minimise negative economic effects.

agent-based model;containment;corona virus;pandemic;scenario analysis;simulation

Journal Article

Wallentin, Gudrun;Kaziyeva, Dana;Reibersdorfer-Adelsberger, Eva

10.34172/ijhpm.2020.130

[Title]: COVID-19 Intervention Scenarios for a Long-term Disease Management. [Abstract]: BACKGROUND: The first outbreak of coronavirus disease 2019 (COVID-19) was successfully restrained in many countries around the world by means of a severe lockdown. Now, we are entering the second phase of the pandemics in which the spread of the virus needs to be contained within the limits that national health systems can cope with. This second phase of the epidemics is expected to last until a vaccination is available or herd immunity is reached. Long-term management strategies thus need to be developed. METHODS: In this paper we present a new agent-based simulation model "COVID-19 ABM" with which we simulate 4 alternative scenarios for the second "new normality" phase that can help decision-makers to take adequate control and intervention measures. RESULTS: The scenarios resulted in distinctly different outcomes. A continued lockdown could regionally eradicate the virus within a few months, whereas a relaxation back to 80% of former activity-levels was followed by a second outbreak. Contact-tracing as well as adaptive response strategies could keep COVID-19 within limits. CONCLUSION: The main insights are that low-level voluntary use of tracing apps shows no relevant effects on containing the virus, whereas medium or high-level tracing allows maintaining a considerably higher level of social activity. Adaptive control strategies help in finding the level of least restrictions. A regional approach to adaptive management can further help in fine-tuning the response to regional dynamics and thus minimise negative economic effects. [Keywords]: agent-based model;containment;corona virus;pandemic;scenario analysis;simulation

PLoS One

Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension.

BACKGROUND: The global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease. METHODS AND FINDINGS: We designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78+/-0,06 vs 1,54+/-0,03 p<0.05). In multivariable regression model main predictors of admission to ICU are male gender (OR 1,74 95% CI 1,36-2,22 p<0.0001) and presence of obesity (OR 2,88 95% CI 2,03-4,07 p<0.0001), chronic kidney disease (OR: 1,588; 95%, 1,036-2,434 p<0,05) and hypertension (OR: 1,314; 95% 1,039-1,662; p<0,05). In gender specific analysis, obesity, chronic kidney disease and hypertension are associated with higher rate of admission to ICU among men, whereas in women, obesity (OR: 2,564; 95% CI 1,336-4.920 p<0.0001) and heart failure (OR: 1,775 95% CI: 1,030-3,057) are associated with higher rate of ICU admission. CONCLUSIONS: Our study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04331574.

Clinical Trial;Journal Article;Multicenter Study;Observational Study;Research Support, Non-U.S. Gov't

Iaccarino, Guido;Grassi, Guido;Borghi, Claudio;Carugo, Stefano;Fallo, Francesco;Ferri, Claudio;Giannattasio, Cristina;Grassi, Davide;Letizia, Claudio;Mancusi, Costantino;Minuz, Pietro;Perlini, Stefano;Pucci, Giacomo;Rizzoni, Damiano;Salvetti, Massimo;Sarzani, Riccardo;Sechi, Leonardo;Veglio, Franco;Volpe, Massimo;Muiesan, Maria Lorenza

10.1371/journal.pone.0237297

[Title]: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension. [Abstract]: BACKGROUND: The global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease. METHODS AND FINDINGS: We designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals. Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78+/-0,06 vs 1,54+/-0,03 p<0.05). In multivariable regression model main predictors of admission to ICU are male gender (OR 1,74 95% CI 1,36-2,22 p<0.0001) and presence of obesity (OR 2,88 95% CI 2,03-4,07 p<0.0001), chronic kidney disease (OR: 1,588; 95%, 1,036-2,434 p<0,05) and hypertension (OR: 1,314; 95% 1,039-1,662; p<0,05). In gender specific analysis, obesity, chronic kidney disease and hypertension are associated with higher rate of admission to ICU among men, whereas in women, obesity (OR: 2,564; 95% CI 1,336-4.920 p<0.0001) and heart failure (OR: 1,775 95% CI: 1,030-3,057) are associated with higher rate of ICU admission. CONCLUSIONS: Our study demonstrates that gender is the primary determinant of the disease's severity among COVID-19. Obesity is the condition more often observed among those admitted to ICU within both genders. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04331574. [Keywords]:

Front Immunol

Interferon-alpha2b Treatment for COVID-19.

The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-alpha2b in a cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-alpha2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-alpha2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-alpha2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-alpha2b should be further investigated as a therapy in COVID-19 cases.

ards;covid-19;il-6;inflammation;interferon;viral shedding

Clinical Trial;Journal Article

Zhou, Qiong;Chen, Virginia;Shannon, Casey P;Wei, Xiao-Shan;Xiang, Xuan;Wang, Xu;Wang, Zi-Hao;Tebbutt, Scott J;Kollmann, Tobias R;Fish, Eleanor N

10.3389/fimmu.2020.01061

[Title]: Interferon-alpha2b Treatment for COVID-19. [Abstract]: The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-alpha2b in a cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-alpha2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-alpha2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-alpha2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-alpha2b should be further investigated as a therapy in COVID-19 cases. [Keywords]: ards;covid-19;il-6;inflammation;interferon;viral shedding

Am J Clin Pathol

Humoral Immune Response to SARS-CoV-2.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology tests are clinically useful to document prior SARS-CoV-2 infections. Data are urgently needed to select assays with optimal sensitivity at acceptable specificity for antibody detection. METHODS: A comparative evaluation was performed of 7 commercial SARS-CoV-2 serology assays on 171 sera from 135 subjects with polymerase chain reaction-confirmed SARS-CoV-2 infection (71 hospitalized patients and 64 paucisymptomatic individuals). Kinetics of IgA/IgM/IgG seroconversion to viral N and S protein epitopes were studied from 0 to 54 days after onset of symptoms. Cross-reactivity was verified on 57 prepandemic samples. RESULTS: Wantai SARS-COV-2 Ab ELISA and Orient Gene COVID-19 IgG/IgM Rapid Test showed superior overall sensitivity for detection of SARS-CoV-2 antibodies. Elecsys Anti-SARS-CoV-2 assay and EUROIMMUN Anti-SARS-CoV-2 combined IgG/IgA showed acceptable sensitivity (>95%) vs the consensus result of all assays from 10 days post onset of symptoms. Wantai SARS-COV-2 Ab ELISA, Elecsys Anti-SARS-CoV-2 assay, and Innovita 2019-nCoV Ab rapid test showed least cross-reactivity, resulting in an optimal analytical specificity greater than 98%. CONCLUSIONS: Wantai SARS-COV-2 Ab ELISA and Elecsys Anti-SARS-CoV-2 assays are suitable for sensitive and specific detection of SARS-CoV-2 antibodies from 10 days after onset of symptoms.

antibody;covid-19;coronavirus;paucisymptomatic;sars-cov-2;serology

Journal Article;Research Support, Non-U.S. Gov't

Herroelen, Pauline H;Martens, Geert A;De Smet, Dieter;Swaerts, Koen;Decavele, An-Sofie

10.1093/ajcp/aqaa140

[Title]: Humoral Immune Response to SARS-CoV-2. [Abstract]: OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology tests are clinically useful to document prior SARS-CoV-2 infections. Data are urgently needed to select assays with optimal sensitivity at acceptable specificity for antibody detection. METHODS: A comparative evaluation was performed of 7 commercial SARS-CoV-2 serology assays on 171 sera from 135 subjects with polymerase chain reaction-confirmed SARS-CoV-2 infection (71 hospitalized patients and 64 paucisymptomatic individuals). Kinetics of IgA/IgM/IgG seroconversion to viral N and S protein epitopes were studied from 0 to 54 days after onset of symptoms. Cross-reactivity was verified on 57 prepandemic samples. RESULTS: Wantai SARS-COV-2 Ab ELISA and Orient Gene COVID-19 IgG/IgM Rapid Test showed superior overall sensitivity for detection of SARS-CoV-2 antibodies. Elecsys Anti-SARS-CoV-2 assay and EUROIMMUN Anti-SARS-CoV-2 combined IgG/IgA showed acceptable sensitivity (>95%) vs the consensus result of all assays from 10 days post onset of symptoms. Wantai SARS-COV-2 Ab ELISA, Elecsys Anti-SARS-CoV-2 assay, and Innovita 2019-nCoV Ab rapid test showed least cross-reactivity, resulting in an optimal analytical specificity greater than 98%. CONCLUSIONS: Wantai SARS-COV-2 Ab ELISA and Elecsys Anti-SARS-CoV-2 assays are suitable for sensitive and specific detection of SARS-CoV-2 antibodies from 10 days after onset of symptoms. [Keywords]: antibody;covid-19;coronavirus;paucisymptomatic;sars-cov-2;serology

JAMA Pediatr

Plans of US Parents Regarding School Attendance for Their Children in the Fall of 2020: A National Survey.

Importance: As schools consider reopening for in-person instruction prior to availability of a coronavirus disease 2019 (COVID-19) vaccine, families may be weighing their priorities regarding school attendance. Objective: To characterize the association of planned in-person school attendance during the COVID-19 pandemic with factors, including family socioeconomic characteristics, and parent attitudes and beliefs about their child's school attendance. Design, Setting, and Participants: Cross-sectional survey study. Data were collected from June 2, 2020, to June 5, 2020, weighted to reflect population norms, and analyzed using ordered probit regression. A sample of US parents (of children ages 5-17 years) were recruited using a nonprobability survey panel with stratification by socioeconomic characteristics. Main Outcomes and Measures: The main outcome was parent-reported plan to send their child to school or keep their child home, conditional on their school opening for in-person instruction. Additional measures assessed family socioeconomic characteristics, medical vulnerability, worry about COVID-19 and multisystem inflammatory syndrome, confidence in their child's school, and homeschooling difficulties. Results: The sample of 730 parents was balanced by parent sex (53% women) with successful oversampling for Black (28%; n = 201) and Hispanic (27%; n = 200) participants. In estimates weighted to US population norms, 31% (95% CI, 27% to 34%) of participants indicated they would probably or definitely keep their child home this fall, and 49% indicated that they would probably or definitely send their child to school this fall. Factors associated with planning to keep children home included lower income (38% with incomes <$50000 vs 21% with incomes $100000-$150000 per year; difference, 17%; 95% CI, 9% to 26%), being unemployed (40% unemployed vs 26% employed; difference, 14%; 95% CI, 5% to 25%), and having a flexible job (33% with flexible jobs vs 19% with inflexible jobs; difference, 14%; 95% CI, 5% to 30%). Planning to keep children home was also associated with fear of COVID-19 (B = 0.19; P < .001), fear of multisystem inflammatory syndrome (B = 0.12; P = .04), confidence in schools (B = -0.22; P < .001), and challenges of homeschooling (B = -0.12; P = .01). Race and ethnicity were not significantly associated with plans to keep children home. Conclusions and Relevance: In this survey study, many parents planned to keep children home in fall 2020. Schools need to act soon to address parental concerns and provide options for what will be available for them should they opt to keep their child home. Structural barriers, such as lack of workplace flexibility and potential school-level inequities in implementation of preventive measures, must be acknowledged and addressed where possible.

Journal Article

Kroshus, Emily;Hawrilenko, Matt;Tandon, Pooja S;Christakis, Dimitri A

10.1001/jamapediatrics.2020.3864

[Title]: Plans of US Parents Regarding School Attendance for Their Children in the Fall of 2020: A National Survey. [Abstract]: Importance: As schools consider reopening for in-person instruction prior to availability of a coronavirus disease 2019 (COVID-19) vaccine, families may be weighing their priorities regarding school attendance. Objective: To characterize the association of planned in-person school attendance during the COVID-19 pandemic with factors, including family socioeconomic characteristics, and parent attitudes and beliefs about their child's school attendance. Design, Setting, and Participants: Cross-sectional survey study. Data were collected from June 2, 2020, to June 5, 2020, weighted to reflect population norms, and analyzed using ordered probit regression. A sample of US parents (of children ages 5-17 years) were recruited using a nonprobability survey panel with stratification by socioeconomic characteristics. Main Outcomes and Measures: The main outcome was parent-reported plan to send their child to school or keep their child home, conditional on their school opening for in-person instruction. Additional measures assessed family socioeconomic characteristics, medical vulnerability, worry about COVID-19 and multisystem inflammatory syndrome, confidence in their child's school, and homeschooling difficulties. Results: The sample of 730 parents was balanced by parent sex (53% women) with successful oversampling for Black (28%; n = 201) and Hispanic (27%; n = 200) participants. In estimates weighted to US population norms, 31% (95% CI, 27% to 34%) of participants indicated they would probably or definitely keep their child home this fall, and 49% indicated that they would probably or definitely send their child to school this fall. Factors associated with planning to keep children home included lower income (38% with incomes <$50000 vs 21% with incomes $100000-$150000 per year; difference, 17%; 95% CI, 9% to 26%), being unemployed (40% unemployed vs 26% employed; difference, 14%; 95% CI, 5% to 25%), and having a flexible job (33% with flexible jobs vs 19% with inflexible jobs; difference, 14%; 95% CI, 5% to 30%). Planning to keep children home was also associated with fear of COVID-19 (B = 0.19; P < .001), fear of multisystem inflammatory syndrome (B = 0.12; P = .04), confidence in schools (B = -0.22; P < .001), and challenges of homeschooling (B = -0.12; P = .01). Race and ethnicity were not significantly associated with plans to keep children home. Conclusions and Relevance: In this survey study, many parents planned to keep children home in fall 2020. Schools need to act soon to address parental concerns and provide options for what will be available for them should they opt to keep their child home. Structural barriers, such as lack of workplace flexibility and potential school-level inequities in implementation of preventive measures, must be acknowledged and addressed where possible. [Keywords]:

Respir Res

Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis.

BACKGROUND: Since December 2019, 2019 novel coronavirus pneumonia emerged in Wuhan city and rapidly spread throughout China and even the world. We sought to analyse the clinical characteristics and laboratory findings of some cases with 2019 novel coronavirus pneumonia . METHODS: In this retrospective study, we extracted the data on 95 patients with laboratory-confirmed 2019 novel coronavirus pneumonia in Wuhan Xinzhou District People's Hospital from January 16th to February 25th, 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until March 2th, 2020. RESULTS: Higher temperature, blood leukocyte count, neutrophil count, neutrophil percentage, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, alpha - hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and so were lower lymphocyte count, lymphocyte percentage and total protein level. Age below 40 or above 60 years old, male, higher Creatinine level, and lower platelet count also seemed related to severe 2019 novel coronavirus pneumonia and composite endpoint, however the P values were greater than 0.05, which mean under the same condition studies of larger samples are needed in the future. CONCLUSION: Multiple factors were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and more related studies are needed in the future.

2019 novel coronavirus;clinical characteristics;laboratory findings;pneumonia

Journal Article

Zhang, Gemin;Zhang, Jie;Wang, Bowen;Zhu, Xionglin;Wang, Qiang;Qiu, Shiming

10.1186/s12931-020-01338-8

[Title]: Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis. [Abstract]: BACKGROUND: Since December 2019, 2019 novel coronavirus pneumonia emerged in Wuhan city and rapidly spread throughout China and even the world. We sought to analyse the clinical characteristics and laboratory findings of some cases with 2019 novel coronavirus pneumonia . METHODS: In this retrospective study, we extracted the data on 95 patients with laboratory-confirmed 2019 novel coronavirus pneumonia in Wuhan Xinzhou District People's Hospital from January 16th to February 25th, 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until March 2th, 2020. RESULTS: Higher temperature, blood leukocyte count, neutrophil count, neutrophil percentage, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, alpha - hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and so were lower lymphocyte count, lymphocyte percentage and total protein level. Age below 40 or above 60 years old, male, higher Creatinine level, and lower platelet count also seemed related to severe 2019 novel coronavirus pneumonia and composite endpoint, however the P values were greater than 0.05, which mean under the same condition studies of larger samples are needed in the future. CONCLUSION: Multiple factors were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and more related studies are needed in the future. [Keywords]: 2019 novel coronavirus;clinical characteristics;laboratory findings;pneumonia

Health Place

Spatiotemporal transmission dynamics of the COVID-19 pandemic and its impact on critical healthcare capacity.

The role of geospatial disparities in the dynamics of the COVID-19 pandemic is poorly understood. We developed a spatially-explicit mathematical model to simulate transmission dynamics of COVID-19 disease infection in relation with the uneven distribution of the healthcare capacity in Ohio, U.S. The results showed substantial spatial variation in the spread of the disease, with localized areas showing marked differences in disease attack rates. Higher COVID-19 attack rates experienced in some highly connected and urbanized areas (274 cases per 100,000 people) could substantially impact the critical health care response of these areas regardless of their potentially high healthcare capacity compared to more rural and less connected counterparts (85 cases per 100,000). Accounting for the spatially uneven disease diffusion linked to the geographical distribution of the critical care resources is essential in designing effective prevention and control programmes aimed at reducing the impact of COVID-19 pandemic.

covid-19;critical healthcare capacity;spatial epidemiology;spatially-explicit mathematical model;transport connectivity

Journal Article

Cuadros, Diego F;Xiao, Yanyu;Mukandavire, Zindoga;Correa-Agudelo, Esteban;Hernandez, Andres;Kim, Hana;MacKinnon, Neil J

10.1016/j.healthplace.2020.102404

[Title]: Spatiotemporal transmission dynamics of the COVID-19 pandemic and its impact on critical healthcare capacity. [Abstract]: The role of geospatial disparities in the dynamics of the COVID-19 pandemic is poorly understood. We developed a spatially-explicit mathematical model to simulate transmission dynamics of COVID-19 disease infection in relation with the uneven distribution of the healthcare capacity in Ohio, U.S. The results showed substantial spatial variation in the spread of the disease, with localized areas showing marked differences in disease attack rates. Higher COVID-19 attack rates experienced in some highly connected and urbanized areas (274 cases per 100,000 people) could substantially impact the critical health care response of these areas regardless of their potentially high healthcare capacity compared to more rural and less connected counterparts (85 cases per 100,000). Accounting for the spatially uneven disease diffusion linked to the geographical distribution of the critical care resources is essential in designing effective prevention and control programmes aimed at reducing the impact of COVID-19 pandemic. [Keywords]: covid-19;critical healthcare capacity;spatial epidemiology;spatially-explicit mathematical model;transport connectivity

World J Clin Cases

Hypertransaminasemia in the course of infection with SARS-CoV-2: Incidence and pathogenetic hypothesis.

In patients infected with severe acute respiratory syndrome coronavirus 2, the respiratory symptoms, such as fever, cough and dyspnea, are the most frequent clinical manifestations. These patients may also present with less well-defined symptoms like diarrhea, nausea, vomiting and/or abdominal discomfort both at the time of diagnosis and during the clinical course. In a few cases, these symptoms may also present before the appearance of respiratory symptoms. To penetrate the body, Severe acute respiratory syndrome coronavirus 2 uses ACE2 receptors, which are present not only in respiratory epithelium but also in gastrointestinal mucosa and liver cholangiocytes. In several cases, viral RNA is detectable in the stool of patients with coronavirus disease 2019 (COVID-19). The liver damage seems to show a multifactorial origin. About 2%-11% of patients with COVID-19 have known underlying hepatic pathologies. In 14%-53% of COVID-19 cases, there is an alteration of the indices of liver cytolysis and is more frequently observed in severe forms of COVID-19, especially during hospitalization.

covid-19;coronavirus;hypertransaminasemia;liver;meta-analysis;sars-cov-2

Journal Article;Review

Zippi, Maddalena;Fiorino, Sirio;Occhigrossi, Giuseppe;Hong, Wandong

10.12998/wjcc.v8.i8.1385

[Title]: Hypertransaminasemia in the course of infection with SARS-CoV-2: Incidence and pathogenetic hypothesis. [Abstract]: In patients infected with severe acute respiratory syndrome coronavirus 2, the respiratory symptoms, such as fever, cough and dyspnea, are the most frequent clinical manifestations. These patients may also present with less well-defined symptoms like diarrhea, nausea, vomiting and/or abdominal discomfort both at the time of diagnosis and during the clinical course. In a few cases, these symptoms may also present before the appearance of respiratory symptoms. To penetrate the body, Severe acute respiratory syndrome coronavirus 2 uses ACE2 receptors, which are present not only in respiratory epithelium but also in gastrointestinal mucosa and liver cholangiocytes. In several cases, viral RNA is detectable in the stool of patients with coronavirus disease 2019 (COVID-19). The liver damage seems to show a multifactorial origin. About 2%-11% of patients with COVID-19 have known underlying hepatic pathologies. In 14%-53% of COVID-19 cases, there is an alteration of the indices of liver cytolysis and is more frequently observed in severe forms of COVID-19, especially during hospitalization. [Keywords]: covid-19;coronavirus;hypertransaminasemia;liver;meta-analysis;sars-cov-2

Stoch Environ Res Risk Assess

A machine learning forecasting model for COVID-19 pandemic in India.

Coronavirus disease (COVID-19) is an inflammation disease from a new virus. The disease causes respiratory ailment (like influenza) with manifestations, for example, cold, cough and fever, and in progressively serious cases, the problem in breathing. COVID-2019 has been perceived as a worldwide pandemic and a few examinations are being led utilizing different numerical models to anticipate the likely advancement of this pestilence. These numerical models dependent on different factors and investigations are dependent upon potential inclination. Here, we presented a model that could be useful to predict the spread of COVID-2019. We have performed linear regression, Multilayer perceptron and Vector autoregression method for desire on the COVID-19 Kaggle data to anticipate the epidemiological example of the ailment and pace of COVID-2019 cases in India. Anticipated the potential patterns of COVID-19 effects in India dependent on data gathered from Kaggle. With the common data about confirmed, death and recovered cases across India for over the time length helps in anticipating and estimating the not so distant future. For extra assessment or future perspective, case definition and data combination must be kept up persistently.

covid-19;linear regression (lr);multilayer perceptron (mlp);prediction;vector autoregression (var)

Journal Article

Sujath, R;Chatterjee, Jyotir Moy;Hassanien, Aboul Ella

10.1007/s00477-020-01827-8

[Title]: A machine learning forecasting model for COVID-19 pandemic in India. [Abstract]: Coronavirus disease (COVID-19) is an inflammation disease from a new virus. The disease causes respiratory ailment (like influenza) with manifestations, for example, cold, cough and fever, and in progressively serious cases, the problem in breathing. COVID-2019 has been perceived as a worldwide pandemic and a few examinations are being led utilizing different numerical models to anticipate the likely advancement of this pestilence. These numerical models dependent on different factors and investigations are dependent upon potential inclination. Here, we presented a model that could be useful to predict the spread of COVID-2019. We have performed linear regression, Multilayer perceptron and Vector autoregression method for desire on the COVID-19 Kaggle data to anticipate the epidemiological example of the ailment and pace of COVID-2019 cases in India. Anticipated the potential patterns of COVID-19 effects in India dependent on data gathered from Kaggle. With the common data about confirmed, death and recovered cases across India for over the time length helps in anticipating and estimating the not so distant future. For extra assessment or future perspective, case definition and data combination must be kept up persistently. [Keywords]: covid-19;linear regression (lr);multilayer perceptron (mlp);prediction;vector autoregression (var)

Arthritis Rheumatol

Incidence of COVID-19 in Patients With Rheumatic Diseases Treated With Targeted Immunosuppressive Drugs: What Can We Learn From Observational Data?

OBJECTIVE: To describe the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases treated with targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs) compared with that in the general population living in the same Italian region. METHODS: Patients followed up at 2 rheumatology referral centers in Lombardy from February 25, 2020 to April 10, 2020 were invited to participate in a survey designed to identify patients who had confirmed COVID-19, close contact with others with confirmed COVID-19, or symptoms of the infection, and to detect changes in work, behavior, and disease management made in an attempt to prevent infection. The incidence of COVID-19 in the Lombardy population was obtained from the National Institute of Statistics. COVID-19 cases were confirmed by nasopharyngeal swab. RESULTS: The survey was given to 955 patients (531 patients with rheumatoid arthritis, 203 patients with psoriatic arthritis, 181 patients with spondyloarthritis, and 40 patients with connective tissue diseases, vasculitides, or autoinflammatory diseases). These patients had a mean age of 53.7 years, and 67.4% were women. The rate of response to the survey was 98.05%, and the incidence of confirmed COVID-19 cases was consistent with that in the general population (0.62% versus 0.66%; P = 0.92). None of the patients had severe complications or required intensive care treatment, and all of the patients who tested positive for COVID-19 temporarily discontinued ongoing targeted synthetic drug or biologic DMARD therapy. Almost all patients took precautions to prevent the COVID-19 infection (90.6%), and almost all continued treatment with targeted synthetic drugs or biologic DMARDs (93.2%). Disease activity remained stable in 89.5% of patients. CONCLUSION: Our results reflected the attitude of patients with rheumatic diseases regarding the prevention of the infection while maintaining their long-term treatment regimens. The incidence and severity of COVID-19 in patients treated with targeted synthetic drugs or biologic DMARDs was not significantly different from that in the general population in the same region.

Journal Article

Favalli, Ennio Giulio;Monti, Sara;Ingegnoli, Francesca;Balduzzi, Silvia;Caporali, Roberto;Montecucco, Carlomaurizio

10.1002/art.41388

[Title]: Incidence of COVID-19 in Patients With Rheumatic Diseases Treated With Targeted Immunosuppressive Drugs: What Can We Learn From Observational Data? [Abstract]: OBJECTIVE: To describe the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases treated with targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs) compared with that in the general population living in the same Italian region. METHODS: Patients followed up at 2 rheumatology referral centers in Lombardy from February 25, 2020 to April 10, 2020 were invited to participate in a survey designed to identify patients who had confirmed COVID-19, close contact with others with confirmed COVID-19, or symptoms of the infection, and to detect changes in work, behavior, and disease management made in an attempt to prevent infection. The incidence of COVID-19 in the Lombardy population was obtained from the National Institute of Statistics. COVID-19 cases were confirmed by nasopharyngeal swab. RESULTS: The survey was given to 955 patients (531 patients with rheumatoid arthritis, 203 patients with psoriatic arthritis, 181 patients with spondyloarthritis, and 40 patients with connective tissue diseases, vasculitides, or autoinflammatory diseases). These patients had a mean age of 53.7 years, and 67.4% were women. The rate of response to the survey was 98.05%, and the incidence of confirmed COVID-19 cases was consistent with that in the general population (0.62% versus 0.66%; P = 0.92). None of the patients had severe complications or required intensive care treatment, and all of the patients who tested positive for COVID-19 temporarily discontinued ongoing targeted synthetic drug or biologic DMARD therapy. Almost all patients took precautions to prevent the COVID-19 infection (90.6%), and almost all continued treatment with targeted synthetic drugs or biologic DMARDs (93.2%). Disease activity remained stable in 89.5% of patients. CONCLUSION: Our results reflected the attitude of patients with rheumatic diseases regarding the prevention of the infection while maintaining their long-term treatment regimens. The incidence and severity of COVID-19 in patients treated with targeted synthetic drugs or biologic DMARDs was not significantly different from that in the general population in the same region. [Keywords]:

Cureus

Acute Liver Failure in a COVID-19 Patient Without any Preexisting Liver Disease.

In December 2019, an outbreak of novel coronavirus started in Wuhan, China, which gradually spread to the entire world. The World Health Organization (WHO) on February 11, 2020, officially announced the name for the disease as coronavirus disease 2019, abbreviated as COVID-19. It is caused by severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2). The WHO declared SARS-CoV-2 as a pandemic on March 11, 2020. SARS-CoV-2 mainly causes fever as well as respiratory symptoms such as cough and shortness of breath. Gastrointestinal/hepatic sequelae such as diarrhea, nausea, vomiting, and elevated liver enzymes have been reported as well. Studies and data so far on coronavirus infections from China, Singapore, and other countries showed that liver enzymes elevation could be seen in 20-50% of cases. More severe disease can correlate with the worsening of liver enzymes. However, acute liver failure in patients with COVID-19 has not been described. Herein we report a case of acute liver failure in an elderly patient with COVID-19 infection who did not have a history of preexisting liver disease.

acute liver failure;covid 19;cytokine release syndrome

Case Reports

Gurala, Dhineshreddy;Al Moussawi, Hassan;Philipose, Jobin;Abergel, Jeffrey R

10.7759/cureus.10045

[Title]: Acute Liver Failure in a COVID-19 Patient Without any Preexisting Liver Disease. [Abstract]: In December 2019, an outbreak of novel coronavirus started in Wuhan, China, which gradually spread to the entire world. The World Health Organization (WHO) on February 11, 2020, officially announced the name for the disease as coronavirus disease 2019, abbreviated as COVID-19. It is caused by severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2). The WHO declared SARS-CoV-2 as a pandemic on March 11, 2020. SARS-CoV-2 mainly causes fever as well as respiratory symptoms such as cough and shortness of breath. Gastrointestinal/hepatic sequelae such as diarrhea, nausea, vomiting, and elevated liver enzymes have been reported as well. Studies and data so far on coronavirus infections from China, Singapore, and other countries showed that liver enzymes elevation could be seen in 20-50% of cases. More severe disease can correlate with the worsening of liver enzymes. However, acute liver failure in patients with COVID-19 has not been described. Herein we report a case of acute liver failure in an elderly patient with COVID-19 infection who did not have a history of preexisting liver disease. [Keywords]: acute liver failure;covid 19;cytokine release syndrome

J Korean Med Sci

Characteristics of Ocular Manifestations of Patients with Coronavirus Disease 2019 in Daegu Province, Korea.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has reportedly affected almost 23 million people, with more than 800 thousand deaths globally. There have been a few reports on the ocular manifestations of COVID-19 patients in China but no reports in Korea. The present study aimed to examine ocular manifestations of COVID-19 patients in Korea. METHODS: COVID-19 patients admitted from March 2020 to April 2020 at Keimyung University Dongsan Hospital and Keimyung University Daegu Dongsan Hospital were reviewed retrospectively for ocular manifestations. During the period of hospitalization, ocular symptoms as well as blood test results were noted and analyzed. Patients were then divided into the first-episode and relapsed group and ocular symptoms were analyzed in the groups. RESULTS: A total of 103 patients were included in this study. Among them, 71patients were in the first-episode group and 32 patients in the relapsed group. No significant differences were determined in terms of positivity of ocular symptoms between the first-episode group (12 patients, 16.9%) and the relapsed group (10 patients, 31.3%, P > 0.05). Symptoms of positive upper respiratory infection and lower creatine phosphokinase were determined to be related to positive ocular symptoms. Conjunctival congestion was noted in seven patients. In the subgroup analysis, the conjunctival congestion-positive patients exhibited higher positivity of upper respiratory infection symptoms (100%) as compared with those in the negative group (40%, P = 0.017). CONCLUSION: Positive upper respiratory infection symptoms and lower creatine phosphokinase were determined to be related to ocular symptoms in COVID-19 patients. Among these patients, positive upper respiratory infection symptoms were associated with conjunctival congestion.

covid-19;conjunctival congestion;coronavirus;ocular manifestations

Journal Article

Lee, You Hyun;Kim, Yu Cheol;Shin, Jae Pil

10.3346/jkms.2020.35.e322

[Title]: Characteristics of Ocular Manifestations of Patients with Coronavirus Disease 2019 in Daegu Province, Korea. [Abstract]: BACKGROUND: The coronavirus disease 2019 (COVID-19) has reportedly affected almost 23 million people, with more than 800 thousand deaths globally. There have been a few reports on the ocular manifestations of COVID-19 patients in China but no reports in Korea. The present study aimed to examine ocular manifestations of COVID-19 patients in Korea. METHODS: COVID-19 patients admitted from March 2020 to April 2020 at Keimyung University Dongsan Hospital and Keimyung University Daegu Dongsan Hospital were reviewed retrospectively for ocular manifestations. During the period of hospitalization, ocular symptoms as well as blood test results were noted and analyzed. Patients were then divided into the first-episode and relapsed group and ocular symptoms were analyzed in the groups. RESULTS: A total of 103 patients were included in this study. Among them, 71patients were in the first-episode group and 32 patients in the relapsed group. No significant differences were determined in terms of positivity of ocular symptoms between the first-episode group (12 patients, 16.9%) and the relapsed group (10 patients, 31.3%, P > 0.05). Symptoms of positive upper respiratory infection and lower creatine phosphokinase were determined to be related to positive ocular symptoms. Conjunctival congestion was noted in seven patients. In the subgroup analysis, the conjunctival congestion-positive patients exhibited higher positivity of upper respiratory infection symptoms (100%) as compared with those in the negative group (40%, P = 0.017). CONCLUSION: Positive upper respiratory infection symptoms and lower creatine phosphokinase were determined to be related to ocular symptoms in COVID-19 patients. Among these patients, positive upper respiratory infection symptoms were associated with conjunctival congestion. [Keywords]: covid-19;conjunctival congestion;coronavirus;ocular manifestations

J Clin Med

Kurarinone Inhibits HCoV-OC43 Infection by Impairing the Virus-Induced Autophagic Flux in MRC-5 Human Lung Cells.

Kurarinone is a prenylated flavonone isolated from the roots of Sophora flavescens. Among its known functions, kurarinone has both anti-apoptotic and anti-inflammatory properties. Coronaviruses (CoVs), including HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2, are the causative agents of respiratory virus infections that range in severity from the common cold to severe pneumonia. There are currently no effective treatments for coronavirus-associated diseases. In this report, we examined the anti-viral impact of kurarinone against infection with the human coronavirus, HCoV-OC43. We found that kurarinone inhibited HCoV-OC43 infection in human lung fibroblast MRC-5 cells in a dose-dependent manner with an IC50 of 3.458 +/- 0.101 muM. Kurarinone inhibited the virus-induced cytopathic effect, as well as extracellular and intracellular viral RNA and viral protein expression. Time-of-addition experiments suggested that kurarinone acted at an early stage of virus infection. Finally, we found that HCoV-OC43 infection increased the autophagic flux in MRC-5 cells; kurarinone inhibited viral replication via its capacity to impair the virus-induced autophagic flux. As such, we suggest that kurarinone may be a useful therapeutic for the treatment of diseases associated with coronavirus infection.

hcov-oc43;lc3;mrc-5 cell;autophagy;coronavirus;infection;kurarinone;p62/sqstm1 protein

Journal Article

Min, Jung Sun;Kim, Dong Eon;Jin, Young-Hee;Kwon, Sunoh

10.3390/jcm9072230

[Title]: Kurarinone Inhibits HCoV-OC43 Infection by Impairing the Virus-Induced Autophagic Flux in MRC-5 Human Lung Cells. [Abstract]: Kurarinone is a prenylated flavonone isolated from the roots of Sophora flavescens. Among its known functions, kurarinone has both anti-apoptotic and anti-inflammatory properties. Coronaviruses (CoVs), including HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2, are the causative agents of respiratory virus infections that range in severity from the common cold to severe pneumonia. There are currently no effective treatments for coronavirus-associated diseases. In this report, we examined the anti-viral impact of kurarinone against infection with the human coronavirus, HCoV-OC43. We found that kurarinone inhibited HCoV-OC43 infection in human lung fibroblast MRC-5 cells in a dose-dependent manner with an IC50 of 3.458 +/- 0.101 muM. Kurarinone inhibited the virus-induced cytopathic effect, as well as extracellular and intracellular viral RNA and viral protein expression. Time-of-addition experiments suggested that kurarinone acted at an early stage of virus infection. Finally, we found that HCoV-OC43 infection increased the autophagic flux in MRC-5 cells; kurarinone inhibited viral replication via its capacity to impair the virus-induced autophagic flux. As such, we suggest that kurarinone may be a useful therapeutic for the treatment of diseases associated with coronavirus infection. [Keywords]: hcov-oc43;lc3;mrc-5 cell;autophagy;coronavirus;infection;kurarinone;p62/sqstm1 protein

Ann Transl Med

Temporal changes of COVID-19 pneumonia by mass evaluation using CT: a retrospective multi-center study.

Background: Coronavirus disease 2019 (COVID-19) has widely spread worldwide and caused a pandemic. Chest CT has been found to play an important role in the diagnosis and management of COVID-19. However, quantitatively assessing temporal changes of COVID-19 pneumonia over time using CT has still not been fully elucidated. The purpose of this study was to perform a longitudinal study to quantitatively assess temporal changes of COVID-19 pneumonia. Methods: This retrospective and multi-center study included patients with laboratory-confirmed COVID-19 infection from 16 hospitals between January 19 and March 27, 2020. Mass was used as an approach to quantitatively measure dynamic changes of pulmonary involvement in patients with COVID-19. Artificial intelligence (AI) was employed as image segmentation and analysis tool for calculating the mass of pulmonary involvement. Results: A total of 581 confirmed patients with 1,309 chest CT examinations were included in this study. The median age was 46 years (IQR, 35-55; range, 4-87 years), and 311 (53.5%) patients were male. The mass of pulmonary involvement peaked on day 10 after the onset of initial symptoms. Furthermore, the mass of pulmonary involvement of older patients (>45 years) was significantly severer (P<0.001) and peaked later (day 11 vs. day 8) than that of younger patients (</=45 years). In addition, there were no significant differences in the peak time (day 10 vs. day 10) and median mass (P=0.679) of pulmonary involvement between male and female. Conclusions: Pulmonary involvement peaked on day 10 after the onset of initial symptoms in patients with COVID-19. Further, pulmonary involvement of older patients was severer and peaked later than that of younger patients. These findings suggest that AI-based quantitative mass evaluation of COVID-19 pneumonia hold great potential for monitoring the disease progression.

coronavirus disease 2019 (covid-19);artificial intelligence (ai);chest ct;temporal changes

Journal Article

Wang, Chao;Huang, Peiyu;Wang, Lihua;Shen, Zhujing;Lin, Bin;Wang, Qiyuan;Zhao, Tongtong;Zheng, Hanpeng;Ji, Wenbin;Gao, Yuantong;Xia, Junli;Cheng, Jianmin;Ma, Jianbing;Liu, Jun;Liu, Yongqiang;Su, Miaoguang;Ruan, Guixiang;Shu, Jiner;Ren, Dawei;Zhao, Zhenhua;Yao, Weigen;Yang, Yunjun;Liu, Bo;Zhang, Minming

10.21037/atm-20-4004

[Title]: Temporal changes of COVID-19 pneumonia by mass evaluation using CT: a retrospective multi-center study. [Abstract]: Background: Coronavirus disease 2019 (COVID-19) has widely spread worldwide and caused a pandemic. Chest CT has been found to play an important role in the diagnosis and management of COVID-19. However, quantitatively assessing temporal changes of COVID-19 pneumonia over time using CT has still not been fully elucidated. The purpose of this study was to perform a longitudinal study to quantitatively assess temporal changes of COVID-19 pneumonia. Methods: This retrospective and multi-center study included patients with laboratory-confirmed COVID-19 infection from 16 hospitals between January 19 and March 27, 2020. Mass was used as an approach to quantitatively measure dynamic changes of pulmonary involvement in patients with COVID-19. Artificial intelligence (AI) was employed as image segmentation and analysis tool for calculating the mass of pulmonary involvement. Results: A total of 581 confirmed patients with 1,309 chest CT examinations were included in this study. The median age was 46 years (IQR, 35-55; range, 4-87 years), and 311 (53.5%) patients were male. The mass of pulmonary involvement peaked on day 10 after the onset of initial symptoms. Furthermore, the mass of pulmonary involvement of older patients (>45 years) was significantly severer (P<0.001) and peaked later (day 11 vs. day 8) than that of younger patients (</=45 years). In addition, there were no significant differences in the peak time (day 10 vs. day 10) and median mass (P=0.679) of pulmonary involvement between male and female. Conclusions: Pulmonary involvement peaked on day 10 after the onset of initial symptoms in patients with COVID-19. Further, pulmonary involvement of older patients was severer and peaked later than that of younger patients. These findings suggest that AI-based quantitative mass evaluation of COVID-19 pneumonia hold great potential for monitoring the disease progression. [Keywords]: coronavirus disease 2019 (covid-19);artificial intelligence (ai);chest ct;temporal changes

Viruses

In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection.

COVID-19 is a pandemic health emergency faced by the entire world. The clinical treatment of the severe acute respiratory syndrome (SARS) CoV-2 is currently based on the experimental administration of HIV antiviral drugs, such as lopinavir, ritonavir, and remdesivir (a nucleotide analogue used for Ebola infection). This work proposes a repurposing process using a database containing approximately 8000 known drugs in synergy structure- and ligand-based studies by means of the molecular docking and descriptor-based protocol. The proposed in silico findings identified new potential SARS CoV-2 main protease (M(PRO)) inhibitors that fit in the catalytic binding site of SARS CoV-2 M(PRO). Several selected structures are NAD-like derivatives, suggesting a relevant role of these molecules in the modulation of SARS CoV-2 infection in conditions of cell chronic oxidative stress. Increased catabolism of NAD(H) during protein ribosylation in the DNA damage repair process may explain the greater susceptibility of the elderly population to the acute respiratory symptoms of COVID-19. The molecular modelling studies proposed herein agree with this hypothesis.

covid-19;drudit web service;hiv-protease;nadh;sars-cov-2 main protease;coronavirus;molecular docking

Journal Article

Martorana, Annamaria;Gentile, Carla;Lauria, Antonino

10.3390/v12080805

[Title]: In Silico Insights into the SARS CoV-2 Main Protease Suggest NADH Endogenous Defences in the Control of the Pandemic Coronavirus Infection. [Abstract]: COVID-19 is a pandemic health emergency faced by the entire world. The clinical treatment of the severe acute respiratory syndrome (SARS) CoV-2 is currently based on the experimental administration of HIV antiviral drugs, such as lopinavir, ritonavir, and remdesivir (a nucleotide analogue used for Ebola infection). This work proposes a repurposing process using a database containing approximately 8000 known drugs in synergy structure- and ligand-based studies by means of the molecular docking and descriptor-based protocol. The proposed in silico findings identified new potential SARS CoV-2 main protease (M(PRO)) inhibitors that fit in the catalytic binding site of SARS CoV-2 M(PRO). Several selected structures are NAD-like derivatives, suggesting a relevant role of these molecules in the modulation of SARS CoV-2 infection in conditions of cell chronic oxidative stress. Increased catabolism of NAD(H) during protein ribosylation in the DNA damage repair process may explain the greater susceptibility of the elderly population to the acute respiratory symptoms of COVID-19. The molecular modelling studies proposed herein agree with this hypothesis. [Keywords]: covid-19;drudit web service;hiv-protease;nadh;sars-cov-2 main protease;coronavirus;molecular docking

J Biol Dyn

Optimal control strategies for the transmission risk of COVID-19.

In this paper, we apply optimal control theory to a novel coronavirus (COVID-19) transmission model given by a system of non-linear ordinary differential equations. Optimal control strategies are obtained by minimizing the number of exposed and infected population considering the cost of implementation. The existence of optimal controls and characterization is established using Pontryagin's Maximum Principle. An expression for the basic reproduction number is derived in terms of control variables. Then the sensitivity of basic reproduction number with respect to model parameters is also analysed. Numerical simulation results demonstrated good agreement with our analytical results. Finally, the findings of this study shows that comprehensive impacts of prevention, intensive medical care and surface disinfection strategies outperform in reducing the disease epidemic with optimum implementation cost.

covid-19;basic reproduction number;mathematical modelling;optimal control;sensitivity analysis

Journal Article;Research Support, Non-U.S. Gov't

Lemecha Obsu, Legesse;Feyissa Balcha, Shiferaw

10.1080/17513758.2020.1788182

[Title]: Optimal control strategies for the transmission risk of COVID-19. [Abstract]: In this paper, we apply optimal control theory to a novel coronavirus (COVID-19) transmission model given by a system of non-linear ordinary differential equations. Optimal control strategies are obtained by minimizing the number of exposed and infected population considering the cost of implementation. The existence of optimal controls and characterization is established using Pontryagin's Maximum Principle. An expression for the basic reproduction number is derived in terms of control variables. Then the sensitivity of basic reproduction number with respect to model parameters is also analysed. Numerical simulation results demonstrated good agreement with our analytical results. Finally, the findings of this study shows that comprehensive impacts of prevention, intensive medical care and surface disinfection strategies outperform in reducing the disease epidemic with optimum implementation cost. [Keywords]: covid-19;basic reproduction number;mathematical modelling;optimal control;sensitivity analysis

J Epidemiol Community Health

It depends on how you ask: measuring bias in population surveys of compliance with COVID-19 public health guidance.

OBJECTIVE: Accurate measurement of compliance with COVID-19 guidance is important for public health policy and communications. Responses to surveys, however, are susceptible to psychological biases, including framing effects and social desirability. Our aim was to measure the effects of these biases on estimates of compliance with public health guidance (eg, hand-washing, social distancing). DESIGN: We conducted two online experiments (n=1800) and varied whether questions were framed positively or negatively (eg, 'I always wash my hands...' vs 'I don't always wash my hands...'). We also varied the degree to which anonymity was assured, via a 'list' experiment. RESULTS: Reported compliance, despite being generally high, was reduced by negatively framing questions and increasing anonymity using a list experiment technique. Effect sizes were large: compliance estimates diminished by up to 17% points and 10% points, respectively. CONCLUSION: Estimates of compliance with COVID-19 guidance vary substantially with how the question is asked. Standard tracking surveys tend to pose questions in ways that lead to higher estimates than alternative approaches. Experimental tests of these surveys offer public health officials greater insight into the range of likely compliance estimates to better inform policy and communications.

cognition;health behaviour;measurement;psychology;public health

Journal Article

Timmons, Shane;McGinnity, Frances;Belton, Cameron;Barjakova, Martina;Lunn, Peter

10.1136/jech-2020-215256

[Title]: It depends on how you ask: measuring bias in population surveys of compliance with COVID-19 public health guidance. [Abstract]: OBJECTIVE: Accurate measurement of compliance with COVID-19 guidance is important for public health policy and communications. Responses to surveys, however, are susceptible to psychological biases, including framing effects and social desirability. Our aim was to measure the effects of these biases on estimates of compliance with public health guidance (eg, hand-washing, social distancing). DESIGN: We conducted two online experiments (n=1800) and varied whether questions were framed positively or negatively (eg, 'I always wash my hands...' vs 'I don't always wash my hands...'). We also varied the degree to which anonymity was assured, via a 'list' experiment. RESULTS: Reported compliance, despite being generally high, was reduced by negatively framing questions and increasing anonymity using a list experiment technique. Effect sizes were large: compliance estimates diminished by up to 17% points and 10% points, respectively. CONCLUSION: Estimates of compliance with COVID-19 guidance vary substantially with how the question is asked. Standard tracking surveys tend to pose questions in ways that lead to higher estimates than alternative approaches. Experimental tests of these surveys offer public health officials greater insight into the range of likely compliance estimates to better inform policy and communications. [Keywords]: cognition;health behaviour;measurement;psychology;public health

J Emerg Med

Point-of-Care Ultrasound in the Evaluation of COVID-19.

BACKGROUND: The novel coronavirus SARS-CoV-2 has caused a pandemic, overwhelming health care systems around the world. Hospitals around the world, including the United States, have been struggling to adapt to the influx of patients with COVID-19, the illness caused by SARS-CoV2, given limited resources and high demand for medical care. OBJECTIVES: This article seeks to provide emergency physicians with a guide to sonographic findings in COVID-19 and an algorithm by which point-of-care lung ultrasound may assist emergency physicians caring for these patients during the SARS-CoV-2 pandemic. DISCUSSION: The studies currently being published have established a typical set of ultrasound findings in COVID-19. Point-of-care lung ultrasound is rapid and accessible in most emergency departments in the United States, and even in many resource-poor settings. CONCLUSION: Point-of-care ultrasound provides numerous benefits to emergency providers caring for patients with COVID-19, including decreasing resource utilization, assisting in diagnosis, guiding management of the critically ill patient, and aiding in rapid triage of patients under investigations for COVID-19.

covid-19;covid;coronavirus;emergency ultrasound;lung ultrasound;point of care ultrasound;thoracic ultrasound

Journal Article;Review

Abrams, Eric R;Rose, Gabriel;Fields, J Matthew;Esener, Dasia

10.1016/j.jemermed.2020.06.032

[Title]: Point-of-Care Ultrasound in the Evaluation of COVID-19. [Abstract]: BACKGROUND: The novel coronavirus SARS-CoV-2 has caused a pandemic, overwhelming health care systems around the world. Hospitals around the world, including the United States, have been struggling to adapt to the influx of patients with COVID-19, the illness caused by SARS-CoV2, given limited resources and high demand for medical care. OBJECTIVES: This article seeks to provide emergency physicians with a guide to sonographic findings in COVID-19 and an algorithm by which point-of-care lung ultrasound may assist emergency physicians caring for these patients during the SARS-CoV-2 pandemic. DISCUSSION: The studies currently being published have established a typical set of ultrasound findings in COVID-19. Point-of-care lung ultrasound is rapid and accessible in most emergency departments in the United States, and even in many resource-poor settings. CONCLUSION: Point-of-care ultrasound provides numerous benefits to emergency providers caring for patients with COVID-19, including decreasing resource utilization, assisting in diagnosis, guiding management of the critically ill patient, and aiding in rapid triage of patients under investigations for COVID-19. [Keywords]: covid-19;covid;coronavirus;emergency ultrasound;lung ultrasound;point of care ultrasound;thoracic ultrasound

J Infect

Longitudinal anti-SARS-CoV-2 antibody profile and neutralization activity of a COVID-19 patient.

We followed-up a mild COVID-19 patient for 91 days and serially monitored his serum antibodies to four SARS-CoV-2 related antigens (NP, RBD, S1 and ECD) and neutralization activities. Our data revealed a profile of serial antibody responses during the progress and a quick decline of neutralization activities after discharge.

Case Reports;Letter

Yin, Shengxia;Tong, Xin;Huang, Aijun;Shen, Han;Li, Yang;Liu, Yong;Wu, Chao;Huang, Rui;Chen, Yuxin

10.1016/j.jinf.2020.06.076

[Title]: Longitudinal anti-SARS-CoV-2 antibody profile and neutralization activity of a COVID-19 patient. [Abstract]: We followed-up a mild COVID-19 patient for 91 days and serially monitored his serum antibodies to four SARS-CoV-2 related antigens (NP, RBD, S1 and ECD) and neutralization activities. Our data revealed a profile of serial antibody responses during the progress and a quick decline of neutralization activities after discharge. [Keywords]:

R I Med J (2013)

COVID-19 and Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) has been reported as a complication of COVID-19. However, the epidemiology, management, and associated outcomes have varied greatly between studies. The pathophysiology remains unclear. Summary: The etiology of AKI in the setting of COVID-19 appears multifactorial. Systemic effects of sepsis, inflammation, and vascular injury likely play some role. Furthermore, SARS-CoV-2 binds to the angiotensin-converting enzyme 2 receptor, highly expressed in the kidney, providing a route for direct infection. Older age, baseline comorbidities, and respiratory failure are strong risk factors for the development of AKI. Regardless of etiology, AKI carries a significantly increased risk for in-hospital mortality, especially in those with critical illness. Currently, management of AKI in patients with COVID-19 remains supportive. Key Messages: AKI is common in patients with COVID-19. Future studies are needed to examine the response to anti-viral treatment as well as long-term renal outcomes in patients with AKI.

ace2;covid-19;acute kidney injury

Journal Article

Lynch, Matthew R;Tang, Jie

[Title]: COVID-19 and Kidney Injury. [Abstract]: BACKGROUND: Acute kidney injury (AKI) has been reported as a complication of COVID-19. However, the epidemiology, management, and associated outcomes have varied greatly between studies. The pathophysiology remains unclear. Summary: The etiology of AKI in the setting of COVID-19 appears multifactorial. Systemic effects of sepsis, inflammation, and vascular injury likely play some role. Furthermore, SARS-CoV-2 binds to the angiotensin-converting enzyme 2 receptor, highly expressed in the kidney, providing a route for direct infection. Older age, baseline comorbidities, and respiratory failure are strong risk factors for the development of AKI. Regardless of etiology, AKI carries a significantly increased risk for in-hospital mortality, especially in those with critical illness. Currently, management of AKI in patients with COVID-19 remains supportive. Key Messages: AKI is common in patients with COVID-19. Future studies are needed to examine the response to anti-viral treatment as well as long-term renal outcomes in patients with AKI. [Keywords]: ace2;covid-19;acute kidney injury

Cureus

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management.

As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. This review focuses on literature published in year 2020 on the virus-induced cardiovascular damage with intention to better understand pathophysiology of this process, its impact on clinical outcomes, and available therapies. Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia. Comorbidities, especially underling heart disease, make patients more predisposed to severe cardiovascular damage. COVID-19 patients who develop myocardial injury have a higher mortality rate compared to those who do not. During the pandemic, percutaneous coronary intervention (PCI) should remain the standard of care for patients with ST segment elevation myocardial infarction (STEMI). On the other hand, in order to limit healthcare worker exposure, patients with non-ST segment elevation myocardial infarction (NSTEMI) should be managed with stabilization strategies if hemodynamically stable. Monitoring hospitalized COVID-19 patients with high sensitivity troponin can help screen for severe complications and detect them early. Use of multiple investigational drugs with uncertain cardiac safety profiles in COVID-19 patients requires continuous cardiac monitoring. Notch signaling pathway therapy along with anti-viral agents, interleukin-6 inhibitors, and convalescent serum are possible treatment options to better control the inflammatory state that drives the cardiac damage.

cardiomyopathy;covid-19;sars-cov-2;takotsubo

Journal Article;Review

Turshudzhyan, Alla

10.7759/cureus.8543

[Title]: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management. [Abstract]: As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. This review focuses on literature published in year 2020 on the virus-induced cardiovascular damage with intention to better understand pathophysiology of this process, its impact on clinical outcomes, and available therapies. Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia. Comorbidities, especially underling heart disease, make patients more predisposed to severe cardiovascular damage. COVID-19 patients who develop myocardial injury have a higher mortality rate compared to those who do not. During the pandemic, percutaneous coronary intervention (PCI) should remain the standard of care for patients with ST segment elevation myocardial infarction (STEMI). On the other hand, in order to limit healthcare worker exposure, patients with non-ST segment elevation myocardial infarction (NSTEMI) should be managed with stabilization strategies if hemodynamically stable. Monitoring hospitalized COVID-19 patients with high sensitivity troponin can help screen for severe complications and detect them early. Use of multiple investigational drugs with uncertain cardiac safety profiles in COVID-19 patients requires continuous cardiac monitoring. Notch signaling pathway therapy along with anti-viral agents, interleukin-6 inhibitors, and convalescent serum are possible treatment options to better control the inflammatory state that drives the cardiac damage. [Keywords]: cardiomyopathy;covid-19;sars-cov-2;takotsubo

J Family Med Prim Care

The importance of wearing masks in curtailing the COVID-19 pandemic.

Primary care workers are the first point of contact for patients. Therefore, it is critical for this group of workers to understand the significant role of personal protective equipment and the importance of adhering to proper donning, doffing, and discarding protocols in epidemic control. These measures are crucial in curtailing disease transmission and the overall containment of the contagion.

air-borne;covid-19;corona virus;face mask;infection control;social distancing;virus

Journal Article

Humphreys, Jose

10.4103/jfmpc.jfmpc_578_20

[Title]: The importance of wearing masks in curtailing the COVID-19 pandemic. [Abstract]: Primary care workers are the first point of contact for patients. Therefore, it is critical for this group of workers to understand the significant role of personal protective equipment and the importance of adhering to proper donning, doffing, and discarding protocols in epidemic control. These measures are crucial in curtailing disease transmission and the overall containment of the contagion. [Keywords]: air-borne;covid-19;corona virus;face mask;infection control;social distancing;virus

Clin Cardiol

On-demand mobile health infrastructures to allow comprehensive remote atrial fibrillation and risk factor management through teleconsultation.

BACKGROUND: Although novel teleconsultation solutions can deliver remote situations that are relatively similar to face-to-face interaction, remote assessment of heart rate and rhythm as well as risk factors remains challenging in patients with atrial fibrillation (AF). HYPOTHESIS: Mobile health (mHealth) solutions can support remote AF management. METHODS: Herein, we discuss available mHealth tools and strategies on how to incorporate the remote assessment of heart rate, rhythm and risk factors to allow comprehensive AF management through teleconsultation. RESULTS: Particularly, in the light of the coronavirus disease 2019 (COVID-19) pandemic, there is decreased capacity to see patients in the outpatient clinic and mHealth has become an important component of many AF outpatient clinics. Several validated mHealth solutions are available for remote heart rate and rhythm monitoring as well as for risk factor assessment. mHealth technologies can be used for (semi-)continuous longitudinal monitoring or for short-term on-demand monitoring, dependent on the respective requirements and clinical scenarios. As a possible solution to improve remote AF care through teleconsultation, we introduce the on-demand TeleCheck-AF mHealth approach that allows remote app-based assessment of heart rate and rhythm around teleconsultations, which has been developed and implemented during the COVID-19 pandemic in Europe. CONCLUSION: Large scale international mHealth projects, such as TeleCheck-AF, will provide insight into the additional value and potential limitations of mHealth strategies to remotely manage AF patients. Such mHealth infrastructures may be well suited within an integrated AF-clinic, which may require redesign of practice and reform of health care systems.

Journal Article;Review

Hermans, Astrid N L;van der Velden, Rachel M J;Gawalko, Monika;Verhaert, Dominique V M;Desteghe, Lien;Duncker, David;Manninger, Martin;Heidbuchel, Hein;Pisters, Ron;Hemels, Martin;Pison, Laurent;Sohaib, Afzal;Sultan, Arian;Steven, Daniel;Wijtvliet, Petra;Tieleman, Robert;Gupta, Dhiraj;Dobrev, Dobromir;Svennberg, Emma;Crijns, Harry J G M;Pluymaekers, Nikki A H A;Hendriks, Jeroen M;Linz, Dominik

10.1002/clc.23469

[Title]: On-demand mobile health infrastructures to allow comprehensive remote atrial fibrillation and risk factor management through teleconsultation. [Abstract]: BACKGROUND: Although novel teleconsultation solutions can deliver remote situations that are relatively similar to face-to-face interaction, remote assessment of heart rate and rhythm as well as risk factors remains challenging in patients with atrial fibrillation (AF). HYPOTHESIS: Mobile health (mHealth) solutions can support remote AF management. METHODS: Herein, we discuss available mHealth tools and strategies on how to incorporate the remote assessment of heart rate, rhythm and risk factors to allow comprehensive AF management through teleconsultation. RESULTS: Particularly, in the light of the coronavirus disease 2019 (COVID-19) pandemic, there is decreased capacity to see patients in the outpatient clinic and mHealth has become an important component of many AF outpatient clinics. Several validated mHealth solutions are available for remote heart rate and rhythm monitoring as well as for risk factor assessment. mHealth technologies can be used for (semi-)continuous longitudinal monitoring or for short-term on-demand monitoring, dependent on the respective requirements and clinical scenarios. As a possible solution to improve remote AF care through teleconsultation, we introduce the on-demand TeleCheck-AF mHealth approach that allows remote app-based assessment of heart rate and rhythm around teleconsultations, which has been developed and implemented during the COVID-19 pandemic in Europe. CONCLUSION: Large scale international mHealth projects, such as TeleCheck-AF, will provide insight into the additional value and potential limitations of mHealth strategies to remotely manage AF patients. Such mHealth infrastructures may be well suited within an integrated AF-clinic, which may require redesign of practice and reform of health care systems. [Keywords]:

MMWR Morb Mortal Wkly Rep

Absence of Apparent Transmission of SARS-CoV-2 from Two Stylists After Exposure at a Hair Salon with a Universal Face Covering Policy - Springfield, Missouri, May 2020.

On May 12, 2020 (day 0), a hair stylist at salon A in Springfield, Missouri (stylist A), developed respiratory symptoms and continued working with clients until day 8, when the stylist received a positive test result for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). A second hair stylist (stylist B), who had been exposed to stylist A, developed respiratory symptoms on May 15, 2020 (day 3), and worked with clients at salon A until day 8 before seeking testing for SARS-CoV-2, which returned a positive result on day 10. A total of 139 clients were directly serviced by stylists A and B from the time they developed symptoms until they took leave from work. Stylists A and B and the 139 clients followed the City of Springfield ordinance* and salon A policy recommending the use of face coverings (i.e., surgical masks, N95 respirators,(dagger) or cloth face coverings) for both stylists and clients during their interactions. Other stylists at salon A who worked closely with stylists A and B were identified, quarantined, and monitored daily for 14 days after their last exposure to stylists A or B. None of these stylists reported COVID-19 symptoms. After stylist B received a positive test result on day 10, salon A closed for 3 days to disinfect frequently touched and contaminated areas. After public health contact tracings and 2 weeks of follow-up, no COVID-19 symptoms were identified among the 139 exposed clients or their secondary contacts. The citywide ordinance and company policy might have played a role in preventing spread of SARS-CoV-2 during these exposures. These findings support the role of source control in preventing transmission and can inform the development of public health policy during the COVID-19 pandemic. As stay-at-home orders are lifted, professional and social interactions in the community will present more opportunities for spread of SARS-CoV-2. Broader implementation of masking policies could mitigate the spread of infection in the general population.

Journal Article

Hendrix, M Joshua;Walde, Charles;Findley, Kendra;Trotman, Robin

10.15585/mmwr.mm6928e2

[Title]: Absence of Apparent Transmission of SARS-CoV-2 from Two Stylists After Exposure at a Hair Salon with a Universal Face Covering Policy - Springfield, Missouri, May 2020. [Abstract]: On May 12, 2020 (day 0), a hair stylist at salon A in Springfield, Missouri (stylist A), developed respiratory symptoms and continued working with clients until day 8, when the stylist received a positive test result for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). A second hair stylist (stylist B), who had been exposed to stylist A, developed respiratory symptoms on May 15, 2020 (day 3), and worked with clients at salon A until day 8 before seeking testing for SARS-CoV-2, which returned a positive result on day 10. A total of 139 clients were directly serviced by stylists A and B from the time they developed symptoms until they took leave from work. Stylists A and B and the 139 clients followed the City of Springfield ordinance* and salon A policy recommending the use of face coverings (i.e., surgical masks, N95 respirators,(dagger) or cloth face coverings) for both stylists and clients during their interactions. Other stylists at salon A who worked closely with stylists A and B were identified, quarantined, and monitored daily for 14 days after their last exposure to stylists A or B. None of these stylists reported COVID-19 symptoms. After stylist B received a positive test result on day 10, salon A closed for 3 days to disinfect frequently touched and contaminated areas. After public health contact tracings and 2 weeks of follow-up, no COVID-19 symptoms were identified among the 139 exposed clients or their secondary contacts. The citywide ordinance and company policy might have played a role in preventing spread of SARS-CoV-2 during these exposures. These findings support the role of source control in preventing transmission and can inform the development of public health policy during the COVID-19 pandemic. As stay-at-home orders are lifted, professional and social interactions in the community will present more opportunities for spread of SARS-CoV-2. Broader implementation of masking policies could mitigate the spread of infection in the general population. [Keywords]:

Indian J Med Res

Coronavirus disease 2019 in children: Clinical & epidemiological implications.

Despite the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there are limited data emerging in children. This review provides an update on clinical features, diagnosis, epidemiology, management and prevention of coronavirus disease 2019 (COVID-19) in children. Specific characteristics noted in children and their implications in disease management as well as transmission control are highlighted. Besides respiratory symptoms, gastrointestinal and atypical features such as chilblains, neurological symptoms and multisystem inflammation are also reported. Younger infants and those with comorbidity were found to be at risk of severe illness. Infected pregnant women and neonates were reported to have good prognosis. It is possible to manage the children with mild disease at home, with strict infection prevention control measures; severely affected require respiratory support and intensive care management. There are anecdotal reports of using antiviral and immunomodulatory drugs, benefit of which needs to be confirmed in clinical trials. A significant percentage of asymptomatic infection in children has epidemiological implication as these may act as links in transmission chain in the community. There is a need for systematic data on extra-pulmonary manifestations and atypical features, risk factors of severity, role of imaging and biomarkers, testing and management strategies and trials with antivirals and immunomodulatory drugs in children. The psychosocial effects of quarantine, closure of schools, lack of play activities and impact of lockdown need to be addressed. Understanding the biological basis for the profound age-dependent differential outcome of COVID-19 infection is important. Elucidating the protective mechanisms in children may aid in developing novel treatment strategies.

covid-2019;children;sars-cov-2;clinical features;epidemiology;prevention;severity of illness;treatment

Journal Article;Review

Kuttiatt, Vijesh Sreedhar;Abraham, Philip Raj;Menon, Ramesh P;Vaidya, Pankaj C;Rahi, Manju

10.4103/ijmr.IJMR_977_20

[Title]: Coronavirus disease 2019 in children: Clinical & epidemiological implications. [Abstract]: Despite the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there are limited data emerging in children. This review provides an update on clinical features, diagnosis, epidemiology, management and prevention of coronavirus disease 2019 (COVID-19) in children. Specific characteristics noted in children and their implications in disease management as well as transmission control are highlighted. Besides respiratory symptoms, gastrointestinal and atypical features such as chilblains, neurological symptoms and multisystem inflammation are also reported. Younger infants and those with comorbidity were found to be at risk of severe illness. Infected pregnant women and neonates were reported to have good prognosis. It is possible to manage the children with mild disease at home, with strict infection prevention control measures; severely affected require respiratory support and intensive care management. There are anecdotal reports of using antiviral and immunomodulatory drugs, benefit of which needs to be confirmed in clinical trials. A significant percentage of asymptomatic infection in children has epidemiological implication as these may act as links in transmission chain in the community. There is a need for systematic data on extra-pulmonary manifestations and atypical features, risk factors of severity, role of imaging and biomarkers, testing and management strategies and trials with antivirals and immunomodulatory drugs in children. The psychosocial effects of quarantine, closure of schools, lack of play activities and impact of lockdown need to be addressed. Understanding the biological basis for the profound age-dependent differential outcome of COVID-19 infection is important. Elucidating the protective mechanisms in children may aid in developing novel treatment strategies. [Keywords]: covid-2019;children;sars-cov-2;clinical features;epidemiology;prevention;severity of illness;treatment

Nature

Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis.

Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic(1). The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes(1). Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a-C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a-C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.

Journal Article;Research Support, Non-U.S. Gov't

Carvelli, Julien;Demaria, Olivier;Vely, Frederic;Batista, Luciana;Chouaki Benmansour, Nassima;Fares, Joanna;Carpentier, Sabrina;Thibult, Marie-Laure;Morel, Ariane;Remark, Romain;Andre, Pascale;Represa, Agnes;Piperoglou, Christelle;Cordier, Pierre Yves;Le Dault, Erwan;Guervilly, Christophe;Simeone, Pierre;Gainnier, Marc;Morel, Yannis;Ebbo, Mikael;Schleinitz, Nicolas;Vivier, Eric

10.1038/s41586-020-2600-6

[Title]: Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis. [Abstract]: Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic(1). The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes(1). Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a-C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a-C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19. [Keywords]:

Int J Mol Sci

Products of Oxidative Guanine Damage Form Base Pairs with Guanine.

Among the natural bases, guanine is the most oxidizable base. The damage caused by oxidation of guanine, commonly referred to as oxidative guanine damage, results in the formation of several products, including 2,5-diamino-4H-imidazol-4-one (Iz), 2,2,4-triamino-5(2H)-oxazolone (Oz), guanidinoformimine (Gf), guanidinohydantoin/iminoallantoin (Gh/Ia), spiroiminodihydantoin (Sp), 5-carboxamido-5-formamido-2-iminohydantoin (2Ih), urea (Ua), 5-guanidino-4-nitroimidazole (NI), spirodi(iminohydantoin) (5-Si and 8-Si), triazine, the M+7 product, other products by peroxynitrite, alkylated guanines, and 8,5'-cyclo-2'-deoxyguanosine (cG). Herein, we summarize the present knowledge about base pairs containing the products of oxidative guanine damage and guanine. Of these products, Iz is involved in G-C transversions. Oz, Gh/Ia, and Sp form preferably Oz:G, Gh/Ia:G, and Sp:G base pairs in some cases. An involvement of Gf, 2Ih, Ua, 5-Si, 8-Si, triazine, the M+7 product, and 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid (HICA) in G-C transversions requires further experiments. In addition, we describe base pairs that target the RNA-dependent RNA polymerase (RdRp) of RNA viruses and describe implications for the 2019 novel coronavirus (SARS-CoV-2): When products of oxidative guanine damage are adapted for the ribonucleoside analogs, mimics of oxidative guanine damages, which can form base pairs, may become antiviral agents for SARS-CoV-2.

2019 novel coronavirus;g-c transversions;sars-cov-2;base incorporation;base pair;oxidative guanine damage

Journal Article;Review

Kino, Katsuhito;Kawada, Taishu;Hirao-Suzuki, Masayo;Morikawa, Masayuki;Miyazawa, Hiroshi

10.3390/ijms21207645

[Title]: Products of Oxidative Guanine Damage Form Base Pairs with Guanine. [Abstract]: Among the natural bases, guanine is the most oxidizable base. The damage caused by oxidation of guanine, commonly referred to as oxidative guanine damage, results in the formation of several products, including 2,5-diamino-4H-imidazol-4-one (Iz), 2,2,4-triamino-5(2H)-oxazolone (Oz), guanidinoformimine (Gf), guanidinohydantoin/iminoallantoin (Gh/Ia), spiroiminodihydantoin (Sp), 5-carboxamido-5-formamido-2-iminohydantoin (2Ih), urea (Ua), 5-guanidino-4-nitroimidazole (NI), spirodi(iminohydantoin) (5-Si and 8-Si), triazine, the M+7 product, other products by peroxynitrite, alkylated guanines, and 8,5'-cyclo-2'-deoxyguanosine (cG). Herein, we summarize the present knowledge about base pairs containing the products of oxidative guanine damage and guanine. Of these products, Iz is involved in G-C transversions. Oz, Gh/Ia, and Sp form preferably Oz:G, Gh/Ia:G, and Sp:G base pairs in some cases. An involvement of Gf, 2Ih, Ua, 5-Si, 8-Si, triazine, the M+7 product, and 4-hydroxy-2,5-dioxo-imidazolidine-4-carboxylic acid (HICA) in G-C transversions requires further experiments. In addition, we describe base pairs that target the RNA-dependent RNA polymerase (RdRp) of RNA viruses and describe implications for the 2019 novel coronavirus (SARS-CoV-2): When products of oxidative guanine damage are adapted for the ribonucleoside analogs, mimics of oxidative guanine damages, which can form base pairs, may become antiviral agents for SARS-CoV-2. [Keywords]: 2019 novel coronavirus;g-c transversions;sars-cov-2;base incorporation;base pair;oxidative guanine damage

JACC Case Rep

Shared Decision Making in Cardiac Transplantation During the COVID-19 Pandemic: Patient Refusal of Transplantation.

Shared decision making with patients in advanced heart failure is critical when making decisions on therapies such as left ventricular assist device implantation and cardiac transplantation. We describe a case wherein the risks of coronavirus disease-2019 affected the decision of a patient regarding proceeding with cardiac transplantation. (Level of Difficulty: Beginner.).

covid-19, coronavirus disease-2019;lvad, left ventricular assist device;sdm, shared decision making;unos, united network for organ sharing;cardiac transplant;cardiomyopathy;chronic heart failure

Case Reports

Chaudhry, Sunit-Preet;Salerno, Christopher T;Ravichandran, Ashwin K;Walsh, Mary Norine

10.1016/j.jaccas.2020.06.004

[Title]: Shared Decision Making in Cardiac Transplantation During the COVID-19 Pandemic: Patient Refusal of Transplantation. [Abstract]: Shared decision making with patients in advanced heart failure is critical when making decisions on therapies such as left ventricular assist device implantation and cardiac transplantation. We describe a case wherein the risks of coronavirus disease-2019 affected the decision of a patient regarding proceeding with cardiac transplantation. (Level of Difficulty: Beginner.). [Keywords]: covid-19, coronavirus disease-2019;lvad, left ventricular assist device;sdm, shared decision making;unos, united network for organ sharing;cardiac transplant;cardiomyopathy;chronic heart failure

JCO Glob Oncol

Dual Challenge of Cancer and COVID-19: Impact on Health Care and Socioeconomic Systems in Asia Pacific.

Coronavirus or COVID-19 is caused by severe acute respiratory syndrome coronavirus 2. The COVID-19 pandemic has resulted in social and economic disruption throughout the entire world. Each country is being challenged. Although much of the world's focus has been on the rapid spread in Italy, Spain, and the United States, the potential impact on the world's poor, a majority of whom are living in Asia, could be devastating. Asia has the world's most densely populated cities, and its developing countries are facing challenges in their socioeconomic and health care systems. COVID-19 is quickly overwhelming the fragile and overstretched health systems of low- and low- to middle-income countries. With its aging population having chronic diseases and the growing burden of cancer, Asia is facing the dual challenge of controlling the spread of COVID-19 and at the same time providing and maintaining cancer care.

Journal Article

De Guzman, Roselle;Malik, Monica

10.1200/GO.20.00227

[Title]: Dual Challenge of Cancer and COVID-19: Impact on Health Care and Socioeconomic Systems in Asia Pacific. [Abstract]: Coronavirus or COVID-19 is caused by severe acute respiratory syndrome coronavirus 2. The COVID-19 pandemic has resulted in social and economic disruption throughout the entire world. Each country is being challenged. Although much of the world's focus has been on the rapid spread in Italy, Spain, and the United States, the potential impact on the world's poor, a majority of whom are living in Asia, could be devastating. Asia has the world's most densely populated cities, and its developing countries are facing challenges in their socioeconomic and health care systems. COVID-19 is quickly overwhelming the fragile and overstretched health systems of low- and low- to middle-income countries. With its aging population having chronic diseases and the growing burden of cancer, Asia is facing the dual challenge of controlling the spread of COVID-19 and at the same time providing and maintaining cancer care. [Keywords]:

Head Neck

Tobacco use and vaping in the COVID-19 era.

Health crises have become a popular topic of discussion. In the wave of the ongoing pandemic, experts have suggested the role of vaping and other tobacco product use exemplifying the vulnerability of the population to contract the COVID-19. We discuss some of the events that led up to these conclusions and also offer a unique insight into another form of tobacco use that is potentially propagating its spread especially in the South Asian region-chewed tobacco. Both of these have been a perennial issue that head and neck cancer surgeons have been dealing with. Governments and head and neck cancer care providers now have an opportunity to deal with a common enemy in the midst of this pandemic.

covid-19;coronavirus;smokeless tobacco;tobacco;vaping

Journal Article;Review

Singh, Arjun Gurmeet;Chaturvedi, Pankaj

10.1002/hed.26208

[Title]: Tobacco use and vaping in the COVID-19 era. [Abstract]: Health crises have become a popular topic of discussion. In the wave of the ongoing pandemic, experts have suggested the role of vaping and other tobacco product use exemplifying the vulnerability of the population to contract the COVID-19. We discuss some of the events that led up to these conclusions and also offer a unique insight into another form of tobacco use that is potentially propagating its spread especially in the South Asian region-chewed tobacco. Both of these have been a perennial issue that head and neck cancer surgeons have been dealing with. Governments and head and neck cancer care providers now have an opportunity to deal with a common enemy in the midst of this pandemic. [Keywords]: covid-19;coronavirus;smokeless tobacco;tobacco;vaping

Vaccine

Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines.

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of "disease enhancement" has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.

animal models;covid-19;enhanced disease;mers-cov vaccine;sars-cov-1 vaccine;sars-cov-2;sars-cov-2 vaccine;vaccine adjuvants;vaccine safety

Consensus Development Conference;Journal Article;Research Support, Non-U.S. Gov't

Lambert, Paul-Henri;Ambrosino, Donna M;Andersen, Svein R;Baric, Ralph S;Black, Steven B;Chen, Robert T;Dekker, Cornelia L;Didierlaurent, Arnaud M;Graham, Barney S;Martin, Samantha D;Molrine, Deborah C;Perlman, Stanley;Picard-Fraser, Philip A;Pollard, Andrew J;Qin, Chuan;Subbarao, Kanta;Cramer, Jakob P

10.1016/j.vaccine.2020.05.064

[Title]: Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines. [Abstract]: A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of "disease enhancement" has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development. [Keywords]: animal models;covid-19;enhanced disease;mers-cov vaccine;sars-cov-1 vaccine;sars-cov-2;sars-cov-2 vaccine;vaccine adjuvants;vaccine safety

Clin Microbiol Infect

Outcomes of persons with coronavirus disease 2019 in hospitals with and without standard treatment with (hydroxy)chloroquine.

OBJECTIVE: To compare survival of individuals with coronavirus disease 2019 (COVID-19) treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. METHODS: We analysed data of COVID-19 patients treated in nine hospitals in the Netherlands. Inclusion dates ranged from 27 February to 15 May 2020, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated patients with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox regression with adjustment for age, sex and covariates based on premorbid health, disease severity and the use of steroids for adult respiratory distress syndrome, including dexamethasone. RESULTS: Among 1949 individuals, 21-day mortality was 21.5% in 1596 patients treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 15.0% in 353 patients treated in hospitals that did not. In the adjusted Cox regression models this difference disappeared, with an adjusted hazard ratio of 1.09 (95% CI 0.81-1.47). When stratified by treatment actually received in individual patients, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95% CI 1.24-2.02) in the full model. CONCLUSIONS: After adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in hospitalised patients with COVID-19.

chloroquine;coronavirus disease 2019;hydroxychloroquine;mortality;severe acute respiratory syndrome coronavirus 2

Comparative Study;Journal Article;Multicenter Study

Peters, Edgar Jg;Collard, Didier;Van Assen, Sander;Beudel, Martijn;Bomers, Marije K;Buijs, Jacqueline;De Haan, Lianne R;De Ruijter, Wouter;Douma, Renee A;Elbers, Paul Wg;Goorhuis, Abraham;Gritters van den Oever, Niels C;Knarren, Lieve Ghh;Moeniralam, Hazra S;Mostard, Remy Lm;Quanjel, Marian Jr;Reidinga, Auke C;Renckens, Roos;Van Den Bergh, Joop Pw;Vlasveld, Imro N;Sikkens, Jonne J

10.1016/j.cmi.2020.10.004

[Title]: Outcomes of persons with coronavirus disease 2019 in hospitals with and without standard treatment with (hydroxy)chloroquine. [Abstract]: OBJECTIVE: To compare survival of individuals with coronavirus disease 2019 (COVID-19) treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. METHODS: We analysed data of COVID-19 patients treated in nine hospitals in the Netherlands. Inclusion dates ranged from 27 February to 15 May 2020, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated patients with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox regression with adjustment for age, sex and covariates based on premorbid health, disease severity and the use of steroids for adult respiratory distress syndrome, including dexamethasone. RESULTS: Among 1949 individuals, 21-day mortality was 21.5% in 1596 patients treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 15.0% in 353 patients treated in hospitals that did not. In the adjusted Cox regression models this difference disappeared, with an adjusted hazard ratio of 1.09 (95% CI 0.81-1.47). When stratified by treatment actually received in individual patients, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95% CI 1.24-2.02) in the full model. CONCLUSIONS: After adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in hospitalised patients with COVID-19. [Keywords]: chloroquine;coronavirus disease 2019;hydroxychloroquine;mortality;severe acute respiratory syndrome coronavirus 2

Otolaryngol Head Neck Surg

An Otolaryngologist Redeployed to a COVID-19 Intensive Care Unit: Lessons Learned.

The COVID-19 pandemic has placed a significant personnel burden on intensive care units across the globe. Physicians from various specialties, including otolaryngology, have heeded the call and been redeployed to provide support, serving in a capacity outside their usual scope of practice. The author shares personal experience from redeployment and provides a framework for otolaryngologists to maximize their impact while providing high-quality patient care and preserving their personal safety.

covid-19;coronavirus;otolaryngology;redeployment

Journal Article

Dhar, Shumon Ian

10.1177/0194599820931819

[Title]: An Otolaryngologist Redeployed to a COVID-19 Intensive Care Unit: Lessons Learned. [Abstract]: The COVID-19 pandemic has placed a significant personnel burden on intensive care units across the globe. Physicians from various specialties, including otolaryngology, have heeded the call and been redeployed to provide support, serving in a capacity outside their usual scope of practice. The author shares personal experience from redeployment and provides a framework for otolaryngologists to maximize their impact while providing high-quality patient care and preserving their personal safety. [Keywords]: covid-19;coronavirus;otolaryngology;redeployment

Infect Dis Ther

Coronavirus: Update Related to the Current Outbreak of COVID-19.

In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection.

covid-19;coronavirus;infectious disease;mers;pneumonia;public health;sars;sars-cov-2

Journal Article;Review

Gabutti, Giovanni;d'Anchera, Erica;Sandri, Federica;Savio, Marta;Stefanati, Armando

10.1007/s40121-020-00295-5

[Title]: Coronavirus: Update Related to the Current Outbreak of COVID-19. [Abstract]: In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection. [Keywords]: covid-19;coronavirus;infectious disease;mers;pneumonia;public health;sars;sars-cov-2

Heart

Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has produced a significant health burden worldwide, especially in patients with cardiovascular comorbidities. The aim of this systematic review and meta-analysis was to assess the impact of underlying cardiovascular comorbidities and acute cardiac injury on in-hospital mortality risk. METHODS: PubMed, Embase and Web of Science were searched for publications that reported the relationship of underlying cardiovascular disease (CVD), hypertension and myocardial injury with in-hospital fatal outcomes in patients with COVID-19. The ORs were extracted and pooled. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. RESULTS: A total of 10 studies were enrolled in this meta-analysis, including eight studies for CVD, seven for hypertension and eight for acute cardiac injury. The presence of CVD and hypertension was associated with higher odds of in-hospital mortality (unadjusted OR 4.85, 95% CI 3.07 to 7.70; I(2)=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I(2)=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I(2)=71%). CONCLUSION: COVID-19 patients with underlying cardiovascular comorbidities, including CVD and hypertension, may face a greater risk of fatal outcomes. Acute cardiac injury may act as a marker of mortality risk. Given the unadjusted results of our meta-analysis, future research are warranted.

cardiac risk factors and prevention;epidemiology;global health;meta-analysis

Journal Article;Meta-Analysis;Systematic Review

Li, Xintao;Guan, Bo;Su, Tong;Liu, Wei;Chen, Mengyao;Bin Waleed, Khalid;Guan, Xumin;Gary, Tse;Zhu, Zhenyan

10.1136/heartjnl-2020-317062

[Title]: Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis. [Abstract]: BACKGROUND: Coronavirus disease 2019 (COVID-19) has produced a significant health burden worldwide, especially in patients with cardiovascular comorbidities. The aim of this systematic review and meta-analysis was to assess the impact of underlying cardiovascular comorbidities and acute cardiac injury on in-hospital mortality risk. METHODS: PubMed, Embase and Web of Science were searched for publications that reported the relationship of underlying cardiovascular disease (CVD), hypertension and myocardial injury with in-hospital fatal outcomes in patients with COVID-19. The ORs were extracted and pooled. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. RESULTS: A total of 10 studies were enrolled in this meta-analysis, including eight studies for CVD, seven for hypertension and eight for acute cardiac injury. The presence of CVD and hypertension was associated with higher odds of in-hospital mortality (unadjusted OR 4.85, 95% CI 3.07 to 7.70; I(2)=29%; unadjusted OR 3.67, 95% CI 2.31 to 5.83; I(2)=57%, respectively). Acute cardiac injury was also associated with a higher unadjusted odds of 21.15 (95% CI 10.19 to 43.94; I(2)=71%). CONCLUSION: COVID-19 patients with underlying cardiovascular comorbidities, including CVD and hypertension, may face a greater risk of fatal outcomes. Acute cardiac injury may act as a marker of mortality risk. Given the unadjusted results of our meta-analysis, future research are warranted. [Keywords]: cardiac risk factors and prevention;epidemiology;global health;meta-analysis

Int J Antimicrob Agents

Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19.

This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.

azithromycin;covid-19;hydroxychloroquine;lopinavir/ritonavir;qt interval;troponin

Journal Article

Padilla, Sergio;Telenti, Guillermo;Guillen, Lucia;Garcia, Jose A;Garcia-Abellan, Javier;Ding, Carolina;Mora, Antonia;Garcia-Pachon, Eduardo;Gutierrez, Felix;Masia, Mar

10.1016/j.ijantimicag.2020.106142

[Title]: Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19. [Abstract]: This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring. [Keywords]: azithromycin;covid-19;hydroxychloroquine;lopinavir/ritonavir;qt interval;troponin

Eur J Phys Rehabil Med

Cranial nerves impairment in post-acute oropharyngeal dysphagia after COVID-19: a case report.

BACKGROUND: According to literature, after COVID-19, patients may require rehabilitation care because of different degrees of physical impairments. Neurologic disorders are often described but no specific data about post-acute cranial nerves involvement and possible correlation with dysphagia development are yet available. CASE REPORT: The patient is a 69-year-old man who presented acquired weakness and dysphagia with clinical cranial nerves impairment of lingual, IX, X and XII after SARS-CoV-2 infection, without electrophysiological alterations. He underwent rehabilitation program for two months, with slow recovery. However, at discharge residual hypoglossal nerve deficit sign was present. CLINICAL REHABILITATION IMPACT: This single case expands knowledge about clinical picture after SARS-CoV-2 disease. Is important to notice that cranial, particularly bulbar nerves could be involved as late complications. Thus, we discuss about risk factors, the nature of the damage and the impact in dysphagia pathophysiology and recovery. If supported by further studies, this case may help to understand dysphagia features in these patients.

Case Reports;Journal Article

Cavalagli, Angela;Peiti, Greta;Conti, Corrado;Penati, Rachele;Vavassori, Francesca;Taveggia, Giovanni

10.23736/S1973-9087.20.06452-7

[Title]: Cranial nerves impairment in post-acute oropharyngeal dysphagia after COVID-19: a case report. [Abstract]: BACKGROUND: According to literature, after COVID-19, patients may require rehabilitation care because of different degrees of physical impairments. Neurologic disorders are often described but no specific data about post-acute cranial nerves involvement and possible correlation with dysphagia development are yet available. CASE REPORT: The patient is a 69-year-old man who presented acquired weakness and dysphagia with clinical cranial nerves impairment of lingual, IX, X and XII after SARS-CoV-2 infection, without electrophysiological alterations. He underwent rehabilitation program for two months, with slow recovery. However, at discharge residual hypoglossal nerve deficit sign was present. CLINICAL REHABILITATION IMPACT: This single case expands knowledge about clinical picture after SARS-CoV-2 disease. Is important to notice that cranial, particularly bulbar nerves could be involved as late complications. Thus, we discuss about risk factors, the nature of the damage and the impact in dysphagia pathophysiology and recovery. If supported by further studies, this case may help to understand dysphagia features in these patients. [Keywords]:

Am J Trop Med Hyg

Malaria and Parasitic Neglected Tropical Diseases: Potential Syndemics with COVID-19?

The COVID-19 pandemic, caused by SARS-CoV-2, have surpassed 5 million cases globally. Current models suggest that low- and middle-income countries (LMICs) will have a similar incidence but substantially lower mortality rate than high-income countries. However, malaria and neglected tropical diseases (NTDs) are prevalent in LMICs, and coinfections are likely. Both malaria and parasitic NTDs can alter immunologic responses to other infectious agents. Malaria can induce a cytokine storm and pro-coagulant state similar to that seen in severe COVID-19. Consequently, coinfections with malaria parasites and SARS-CoV-2 could result in substantially worse outcomes than mono-infections with either pathogen, and could shift the age pattern of severe COVID-19 to younger age-groups. Enhancing surveillance platforms could provide signals that indicate whether malaria, NTDs, and COVID-19 are syndemics (synergistic epidemics). Based on the prevalence of malaria and NTDs in specific localities, efforts to characterize COVID-19 in LMICs could be expanded by adding testing for malaria and NTDs. Such additional testing would allow the determination of the rates of coinfection and comparison of severity of outcomes by infection status, greatly improving the understanding of the epidemiology of COVID-19 in LMICs and potentially helping to mitigate its impact.

Journal Article

Gutman, Julie R;Lucchi, Naomi W;Cantey, Paul T;Steinhardt, Laura C;Samuels, Aaron M;Kamb, Mary L;Kapella, Bryan K;McElroy, Peter D;Udhayakumar, Venkatachalam;Lindblade, Kim A

10.4269/ajtmh.20-0516

[Title]: Malaria and Parasitic Neglected Tropical Diseases: Potential Syndemics with COVID-19? [Abstract]: The COVID-19 pandemic, caused by SARS-CoV-2, have surpassed 5 million cases globally. Current models suggest that low- and middle-income countries (LMICs) will have a similar incidence but substantially lower mortality rate than high-income countries. However, malaria and neglected tropical diseases (NTDs) are prevalent in LMICs, and coinfections are likely. Both malaria and parasitic NTDs can alter immunologic responses to other infectious agents. Malaria can induce a cytokine storm and pro-coagulant state similar to that seen in severe COVID-19. Consequently, coinfections with malaria parasites and SARS-CoV-2 could result in substantially worse outcomes than mono-infections with either pathogen, and could shift the age pattern of severe COVID-19 to younger age-groups. Enhancing surveillance platforms could provide signals that indicate whether malaria, NTDs, and COVID-19 are syndemics (synergistic epidemics). Based on the prevalence of malaria and NTDs in specific localities, efforts to characterize COVID-19 in LMICs could be expanded by adding testing for malaria and NTDs. Such additional testing would allow the determination of the rates of coinfection and comparison of severity of outcomes by infection status, greatly improving the understanding of the epidemiology of COVID-19 in LMICs and potentially helping to mitigate its impact. [Keywords]:

Ann Intern Med

Managing COVID-19 in a Novel, Rapidly Deployable Community Isolation Quarantine Facility.

Singapore is one of the most densely populated small island-states in the world. During the coronavirus disease 2019 (COVID-19) pandemic, Singapore implemented large-scale institutional isolation units called Community Care Facilities (CCFs) to combat the outbreak in the community by housing low-risk COVID-19 patients from April to August 2020. The CCFs were created rapidly by converting existing public spaces and used a protocolized system, augmented by telemedicine to enable a low health care worker-patient ratio (98 health care workers for 3200 beds), to operate these unique facilities. In the first month, a total of 3758 patients were admitted to 4 halls, 4929 in-house medical consults occurred, 136 patients were transferred to a hospital, 1 patient died 2 weeks after discharge, and no health care workers became infected. This article shares the authors' experience in operating these massive-scale isolation facilities while prioritizing safety for all and ensuring holistic patient care in the face of a public health crisis and lean health care resources.

Journal Article

Chia, Ming Li;Him Chau, Dickson Hong;Lim, Kheng Sit;Yang Liu, Christopher Wei;Tan, Hiang Khoon;Tan, Yan Ru

10.7326/M20-4746

[Title]: Managing COVID-19 in a Novel, Rapidly Deployable Community Isolation Quarantine Facility. [Abstract]: Singapore is one of the most densely populated small island-states in the world. During the coronavirus disease 2019 (COVID-19) pandemic, Singapore implemented large-scale institutional isolation units called Community Care Facilities (CCFs) to combat the outbreak in the community by housing low-risk COVID-19 patients from April to August 2020. The CCFs were created rapidly by converting existing public spaces and used a protocolized system, augmented by telemedicine to enable a low health care worker-patient ratio (98 health care workers for 3200 beds), to operate these unique facilities. In the first month, a total of 3758 patients were admitted to 4 halls, 4929 in-house medical consults occurred, 136 patients were transferred to a hospital, 1 patient died 2 weeks after discharge, and no health care workers became infected. This article shares the authors' experience in operating these massive-scale isolation facilities while prioritizing safety for all and ensuring holistic patient care in the face of a public health crisis and lean health care resources. [Keywords]:

Int Braz J Urol

The impact of COVID-19 in medical practice. A review focused on Urology.

COVID-19 pandemic is a rapidly spreading virus that is changing the World and the way doctors are practicing medicine. The huge number of patients searching for medical care and needing intensive care beds led the health care system to a burnout status especially in places where the care system was already overloaded. In this setting, and also due to the absence of a specific treatment for the disease, health authorities had to opt for recommending or imposing social distancing to relieve the health system and reduce deaths. All other medical specialties non-directly related to the treatment of COVID-19 had to interrupt or strongly reduce their activities in order to give room to seriously ill patients, since no one knows so far the real extent of the virus damage on human body and the consequences of doing non deferrable procedures in this pandemic era. Despite not been a urological disease, the urologist needs to be updated on how to deal with these patients and how to take care of himself and of the medical team he works with. The aim of this article is to review briefly some practical aspects of COVID-19 and its implications in the urological practice in our country.

covid-19 diagnostic testing [supplementary concept];review [publication type];spike protein, sars-cov-2 [supplementary concept]

Journal Article;Review

Mazzucchi, Eduardo;Torricelli, Fabio C M;Vicentini, Fabio C;Marchini, Giovanni S;Danilovic, Alexandre;Batagello, Carlos A;Srougi, Miguel;Nahas, William C

10.1590/S1677-5538.IBJU.2020.99.08

[Title]: The impact of COVID-19 in medical practice. A review focused on Urology. [Abstract]: COVID-19 pandemic is a rapidly spreading virus that is changing the World and the way doctors are practicing medicine. The huge number of patients searching for medical care and needing intensive care beds led the health care system to a burnout status especially in places where the care system was already overloaded. In this setting, and also due to the absence of a specific treatment for the disease, health authorities had to opt for recommending or imposing social distancing to relieve the health system and reduce deaths. All other medical specialties non-directly related to the treatment of COVID-19 had to interrupt or strongly reduce their activities in order to give room to seriously ill patients, since no one knows so far the real extent of the virus damage on human body and the consequences of doing non deferrable procedures in this pandemic era. Despite not been a urological disease, the urologist needs to be updated on how to deal with these patients and how to take care of himself and of the medical team he works with. The aim of this article is to review briefly some practical aspects of COVID-19 and its implications in the urological practice in our country. [Keywords]: covid-19 diagnostic testing [supplementary concept];review [publication type];spike protein, sars-cov-2 [supplementary concept]

J Public Health (Oxf)

The impact of COVID-19 on Bangladeshi readymade garment (RMG) workers.

This paper describes the potential impact of the coronavirus disease 2019 (COVID-19) pandemic on the readymade garment (RMG) workers of Bangladesh. It articulates the RMG workers' existing vulnerability during the COVID-19 pandemic based on currently available evidence and personal conversations/communications with RMG workers. COVID-19 has already impacted RMG workers' health (both physical and mental health status) and wellbeing, and resulted in loss of employment. We argue that the COVID-19 pandemic will have long-lasting effects on the garment workers, especially related to their health issues, financial hardship and inability to pay for essentials such as food, and future employment opportunities. The stakeholders (such as the international retailers/brands, Bangladesh Garment Manufacturers and Exporters Association, Government of Bangladesh) responsible for the global supply chain RMG factories should reconsider the health and overall wellbeing needs of the RMG workers during the ongoing COVID-19 pandemic.

bangladesh;covid-19;crisis;health vulnerabilities;readymade garment workers;starvation

Journal Article

Kabir, Humayun;Maple, Myfanwy;Usher, Kim

10.1093/pubmed/fdaa126

[Title]: The impact of COVID-19 on Bangladeshi readymade garment (RMG) workers. [Abstract]: This paper describes the potential impact of the coronavirus disease 2019 (COVID-19) pandemic on the readymade garment (RMG) workers of Bangladesh. It articulates the RMG workers' existing vulnerability during the COVID-19 pandemic based on currently available evidence and personal conversations/communications with RMG workers. COVID-19 has already impacted RMG workers' health (both physical and mental health status) and wellbeing, and resulted in loss of employment. We argue that the COVID-19 pandemic will have long-lasting effects on the garment workers, especially related to their health issues, financial hardship and inability to pay for essentials such as food, and future employment opportunities. The stakeholders (such as the international retailers/brands, Bangladesh Garment Manufacturers and Exporters Association, Government of Bangladesh) responsible for the global supply chain RMG factories should reconsider the health and overall wellbeing needs of the RMG workers during the ongoing COVID-19 pandemic. [Keywords]: bangladesh;covid-19;crisis;health vulnerabilities;readymade garment workers;starvation

Cardiovasc Intervent Radiol

Interventional Radiology Procedures for COVID-19 Patients: How we Do it.

With astonishing speed, COVID-19 has become a global pandemic. As it is uncertain when the pandemic will be controlled, it is crucial for procedurists of all stripes to be familiar and confident in performing procedures for COVID-19 patients to prevent intra-hospital infection. In this article, we will detail our approach on how to perform interventional procedures for COVID-19 patients at the bedside in the isolation room and with the patient transferred to the interventional radiology centre. These workflows have been developed in conjunction with multiple other stakeholders within our hospital, drawing from valuable lessons we have learnt from the SARS outbreak of 2003.

covid-19;infection control;interventional radiology;policy;procedures;process

Journal Article

Too, Chow Wei;Wen, David Wei;Patel, Ankur;Abdul Syafiq, Abdul Rahman;Liu, Jian;Leong, Sum;Gogna, Apoorva;Lo, Richard Hoau Gong;Tashi, Sonam;Lee, Kristen Alexa;Kumar, Pradesh;Lie, Sui An;Tay, Yoong Chuan;Lee, Lai Chee;Ling, Moi Lin;Tan, Bien Soo;Tay, Kiang Hiong

10.1007/s00270-020-02483-9

[Title]: Interventional Radiology Procedures for COVID-19 Patients: How we Do it. [Abstract]: With astonishing speed, COVID-19 has become a global pandemic. As it is uncertain when the pandemic will be controlled, it is crucial for procedurists of all stripes to be familiar and confident in performing procedures for COVID-19 patients to prevent intra-hospital infection. In this article, we will detail our approach on how to perform interventional procedures for COVID-19 patients at the bedside in the isolation room and with the patient transferred to the interventional radiology centre. These workflows have been developed in conjunction with multiple other stakeholders within our hospital, drawing from valuable lessons we have learnt from the SARS outbreak of 2003. [Keywords]: covid-19;infection control;interventional radiology;policy;procedures;process

J Med Internet Res

Using Reports of Symptoms and Diagnoses on Social Media to Predict COVID-19 Case Counts in Mainland China: Observational Infoveillance Study.

BACKGROUND: Coronavirus disease (COVID-19) has affected more than 200 countries and territories worldwide. This disease poses an extraordinary challenge for public health systems because screening and surveillance capacity is often severely limited, especially during the beginning of the outbreak; this can fuel the outbreak, as many patients can unknowingly infect other people. OBJECTIVE: The aim of this study was to collect and analyze posts related to COVID-19 on Weibo, a popular Twitter-like social media site in China. To our knowledge, this infoveillance study employs the largest, most comprehensive, and most fine-grained social media data to date to predict COVID-19 case counts in mainland China. METHODS: We built a Weibo user pool of 250 million people, approximately half the entire monthly active Weibo user population. Using a comprehensive list of 167 keywords, we retrieved and analyzed around 15 million COVID-19-related posts from our user pool from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify "sick posts," in which users report their own or other people's symptoms and diagnoses related to COVID-19. Using officially reported case counts as the outcome, we then estimated the Granger causality of sick posts and other COVID-19 posts on daily case counts. For a subset of geotagged posts (3.10% of all retrieved posts), we also ran separate predictive models for Hubei province, the epicenter of the initial outbreak, and the rest of mainland China. RESULTS: We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts up to 14 days ahead of official statistics, whereas other COVID-19 posts did not have similar predictive power. For the subset of geotagged posts, we found that the predictive pattern held true for both Hubei province and the rest of mainland China regardless of the unequal distribution of health care resources and the outbreak timeline. CONCLUSIONS: Public social media data can be usefully harnessed to predict infection cases and inform timely responses. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. In addition to monitoring overall search and posting activities, leveraging machine learning approaches and theoretical understanding of information sharing behaviors is a promising approach to identify true disease signals and improve the effectiveness of infoveillance.

covid-19;china;sars-cov-2;weibo;disease surveillance;infectious disease;infodemiology;infoveillance;novel coronavirus;social media;surveillance

Journal Article

Shen, Cuihua;Chen, Anfan;Luo, Chen;Zhang, Jingwen;Feng, Bo;Liao, Wang

10.2196/19421

[Title]: Using Reports of Symptoms and Diagnoses on Social Media to Predict COVID-19 Case Counts in Mainland China: Observational Infoveillance Study. [Abstract]: BACKGROUND: Coronavirus disease (COVID-19) has affected more than 200 countries and territories worldwide. This disease poses an extraordinary challenge for public health systems because screening and surveillance capacity is often severely limited, especially during the beginning of the outbreak; this can fuel the outbreak, as many patients can unknowingly infect other people. OBJECTIVE: The aim of this study was to collect and analyze posts related to COVID-19 on Weibo, a popular Twitter-like social media site in China. To our knowledge, this infoveillance study employs the largest, most comprehensive, and most fine-grained social media data to date to predict COVID-19 case counts in mainland China. METHODS: We built a Weibo user pool of 250 million people, approximately half the entire monthly active Weibo user population. Using a comprehensive list of 167 keywords, we retrieved and analyzed around 15 million COVID-19-related posts from our user pool from November 1, 2019 to March 31, 2020. We developed a machine learning classifier to identify "sick posts," in which users report their own or other people's symptoms and diagnoses related to COVID-19. Using officially reported case counts as the outcome, we then estimated the Granger causality of sick posts and other COVID-19 posts on daily case counts. For a subset of geotagged posts (3.10% of all retrieved posts), we also ran separate predictive models for Hubei province, the epicenter of the initial outbreak, and the rest of mainland China. RESULTS: We found that reports of symptoms and diagnosis of COVID-19 significantly predicted daily case counts up to 14 days ahead of official statistics, whereas other COVID-19 posts did not have similar predictive power. For the subset of geotagged posts, we found that the predictive pattern held true for both Hubei province and the rest of mainland China regardless of the unequal distribution of health care resources and the outbreak timeline. CONCLUSIONS: Public social media data can be usefully harnessed to predict infection cases and inform timely responses. Researchers and disease control agencies should pay close attention to the social media infosphere regarding COVID-19. In addition to monitoring overall search and posting activities, leveraging machine learning approaches and theoretical understanding of information sharing behaviors is a promising approach to identify true disease signals and improve the effectiveness of infoveillance. [Keywords]: covid-19;china;sars-cov-2;weibo;disease surveillance;infectious disease;infodemiology;infoveillance;novel coronavirus;social media;surveillance

Front Med

Coronavirus disease 2019 (COVID-19): a clinical update.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. It caused a total of 80 868 confirmed cases and 3101 deaths in Chinese mainland until March 8, 2020. This novel virus spread mainly through respiratory droplets and close contact. As disease progressed, a series of complications tend to develop, especially in critically ill patients. Pathological findings showed representative features of acute respiratory distress syndrome and involvement of multiple organs. Apart from supportive care, no specific treatment has been established for COVID-19. The efficacy of some promising antivirals, convalescent plasma transfusion, and tocilizumab needs to be investigated by ongoing clinical trials.

clinical characteristics;coronavirus disease 2019;epidemiology;pathology;radiology;treatment

Journal Article;Review

Zhou, Min;Zhang, Xinxin;Qu, Jieming

10.1007/s11684-020-0767-8

[Title]: Coronavirus disease 2019 (COVID-19): a clinical update. [Abstract]: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. It caused a total of 80 868 confirmed cases and 3101 deaths in Chinese mainland until March 8, 2020. This novel virus spread mainly through respiratory droplets and close contact. As disease progressed, a series of complications tend to develop, especially in critically ill patients. Pathological findings showed representative features of acute respiratory distress syndrome and involvement of multiple organs. Apart from supportive care, no specific treatment has been established for COVID-19. The efficacy of some promising antivirals, convalescent plasma transfusion, and tocilizumab needs to be investigated by ongoing clinical trials. [Keywords]: clinical characteristics;coronavirus disease 2019;epidemiology;pathology;radiology;treatment

Technol Forecast Soc Change

COVID-19: A revelation - A reply to Ian Mitroff.

This is a rejoinder of Dr. Ian Mitroff's perspective titled "Corona Virus: A Prime Example of A Wicked Mess". While I agree with Dr. Mitroff on the complexity of the COVID-19 outbreak and the urgency to address it, I disagree with him on points related to the role of wet market in this specific outbreak and whether China had acknowledged the existence of the outbreak. I also consider key highlights of the outbreak are the importance of collaboration across national and state borders and a balance between privacy and public health under such situations.

covid-19;outbreak;privacy;public health

Journal Article;Review

Chen, Zhuo

10.1016/j.techfore.2020.120072

[Title]: COVID-19: A revelation - A reply to Ian Mitroff. [Abstract]: This is a rejoinder of Dr. Ian Mitroff's perspective titled "Corona Virus: A Prime Example of A Wicked Mess". While I agree with Dr. Mitroff on the complexity of the COVID-19 outbreak and the urgency to address it, I disagree with him on points related to the role of wet market in this specific outbreak and whether China had acknowledged the existence of the outbreak. I also consider key highlights of the outbreak are the importance of collaboration across national and state borders and a balance between privacy and public health under such situations. [Keywords]: covid-19;outbreak;privacy;public health

J Gastrointestin Liver Dis

Abnormal Liver Function Tests of Patients with Coronavirus Disease 2019 in Mainland China: A Systematic Review and Meta- Analysis.

AIMS: Comparing the risk of abnormal liver function tests between severe and non-severe patients with coronavirus disease 2019 (COVID-19) by meta-analysis. METHODS: A literature search was conducted using the databases PubMed, Embase, and Cochrane Library. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using fixed- or random-effects models. Publication bias was detected by the Harbord test. RESULTS: We included 8 articles comprising 7,467 COVID-19 patients. When compared between severe and non-severe COVID-19 patients, the pooled ORs of elevated alanine aminotransferase, aspartate aminotransferase, total bilirubin, and lactate dehydrogenase levels were 2.35 (95% CI 1.38-3.98), 3.21 (95% CI 2.59-3.98), 1.87 (95% CI 1.32-2.65), and 4.83 (95% CI 2.90-8.05), respectively. CONCLUSIONS: The severity of COVID-19 is associated with liver damage, and can be a risk factor for abnormal liver function tests.

Journal Article;Meta-Analysis;Systematic Review

Xin, Shengliang;Xu, Jinghang;Yu, Yanyan

10.15403/jgld-2513

[Title]: Abnormal Liver Function Tests of Patients with Coronavirus Disease 2019 in Mainland China: A Systematic Review and Meta- Analysis. [Abstract]: AIMS: Comparing the risk of abnormal liver function tests between severe and non-severe patients with coronavirus disease 2019 (COVID-19) by meta-analysis. METHODS: A literature search was conducted using the databases PubMed, Embase, and Cochrane Library. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using fixed- or random-effects models. Publication bias was detected by the Harbord test. RESULTS: We included 8 articles comprising 7,467 COVID-19 patients. When compared between severe and non-severe COVID-19 patients, the pooled ORs of elevated alanine aminotransferase, aspartate aminotransferase, total bilirubin, and lactate dehydrogenase levels were 2.35 (95% CI 1.38-3.98), 3.21 (95% CI 2.59-3.98), 1.87 (95% CI 1.32-2.65), and 4.83 (95% CI 2.90-8.05), respectively. CONCLUSIONS: The severity of COVID-19 is associated with liver damage, and can be a risk factor for abnormal liver function tests. [Keywords]:

J Phys Chem Lett

In Silico Exploration of the Molecular Mechanism of Clinically Oriented Drugs for Possibly Inhibiting SARS-CoV-2's Main Protease.

Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well-calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the mechanism of binding between the Mpro's pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. By combining the existing experimental results with our computational ones, we revealed an important ligand binding mechanism of the Mpro, demonstrating that the binding stability of a ligand inside the Mpro pocket can be significantly improved if part of the ligand occupies its so-called "anchor" site. Along with the highly potent drugs and/or molecules (such as nelfinavir) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro's inhibitors with a high binding affinity.

Journal Article

Huynh, Tien;Wang, Haoran;Luan, Binquan

10.1021/acs.jpclett.0c00994

[Title]: In Silico Exploration of the Molecular Mechanism of Clinically Oriented Drugs for Possibly Inhibiting SARS-CoV-2's Main Protease. [Abstract]: Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well-calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the mechanism of binding between the Mpro's pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. By combining the existing experimental results with our computational ones, we revealed an important ligand binding mechanism of the Mpro, demonstrating that the binding stability of a ligand inside the Mpro pocket can be significantly improved if part of the ligand occupies its so-called "anchor" site. Along with the highly potent drugs and/or molecules (such as nelfinavir) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro's inhibitors with a high binding affinity. [Keywords]:

A A Pract

Does a Modified Adhesive Respirator Improve the Face Seal for Health Care Workers Who Previously Failed a Fit Test?: A Pilot Study During the Coronavirus Disease 2019 Pandemic.

Approximately 30% of health care workers (HCWs) fail the respirator fit test. Evidence suggests that addressing face leaks in the 3M respirator enhances its fit and improves its efficacy. Between March 31 and April 9, 2020, HCWs who failed fit tests for 3M 1860 and 1860S respirators were invited to retest with an adhesive modification of the 3M respirator. Sixty-eight percent of HCWs who failed the fit test with their first-choice respirator passed with a modified adhesive respirator. To increase the efficacy and safety of 3M respirators, ineffective face seals need substantial improvement in design.

Journal Article

Wardhan, Richa;Brennan, Meghan M;Brown, Holden L;Creech, Trey B

10.1213/XAA.0000000000001264

[Title]: Does a Modified Adhesive Respirator Improve the Face Seal for Health Care Workers Who Previously Failed a Fit Test?: A Pilot Study During the Coronavirus Disease 2019 Pandemic. [Abstract]: Approximately 30% of health care workers (HCWs) fail the respirator fit test. Evidence suggests that addressing face leaks in the 3M respirator enhances its fit and improves its efficacy. Between March 31 and April 9, 2020, HCWs who failed fit tests for 3M 1860 and 1860S respirators were invited to retest with an adhesive modification of the 3M respirator. Sixty-eight percent of HCWs who failed the fit test with their first-choice respirator passed with a modified adhesive respirator. To increase the efficacy and safety of 3M respirators, ineffective face seals need substantial improvement in design. [Keywords]:

Can J Neurol Sci

Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic.

BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

addiction covid;ataxia;axonal transport;covid-19;cerebrovascular events;demyelination;encephalitis;encephalopathy;epilepsy;myelitis;myoclonus;neuro-covid;neuroinvasion;neurotropism;neurovirulence;polyradiculopathy;psychiatric;psychosocial;sars-cov-2;seizures;stroke;therapeutic paradigm shift

Journal Article;Review

Roy, Devlina;Ghosh, Ritwik;Dubey, Souvik;Dubey, Mahua Jana;Benito-Leon, Julian;Kanti Ray, Biman

10.1017/cjn.2020.173

[Title]: Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic. [Abstract]: BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality. [Keywords]: addiction covid;ataxia;axonal transport;covid-19;cerebrovascular events;demyelination;encephalitis;encephalopathy;epilepsy;myelitis;myoclonus;neuro-covid;neuroinvasion;neurotropism;neurovirulence;polyradiculopathy;psychiatric;psychosocial;sars-cov-2;seizures;stroke;therapeutic paradigm shift

Med Intensiva

[Recommendations on cardiopulmonary resuscitation in patients with suspected or confirmed SARS-CoV-2 infection (COVID-19). Executive summary].

The SARS-CoV-2 pandemic has created new scenarios that require modifications to the usual cardiopulmonary resuscitation protocols. The current clinical guidelines on the management of cardiorespiratory arrest do not include recommendations for situations that apply to this context. Therefore, the National Cardiopulmonary Resuscitation Plan of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), in collaboration with the Spanish Group of Pediatric and Neonatal CPR and with the Teaching Life Support in Primary Care program of the Spanish Society of Family and Community Medicine (SEMFyC), have written these recommendations, which are divided into 5 parts that address the main aspects for each healthcare setting. This article consists of an executive summary of them.

covid-19;cardiopulmonary resuscitation;cardiorespiratory arrest;coronavirus;recommendations

Journal Article;Practice Guideline

Rodriguez Yago, M A;Alcalde Mayayo, I;Gomez Lopez, R;Parias Angel, M N;Perez Miranda, A;Canals Aracil, M;Civantos Fuentes, E;Rodriguez Nunez, A;Manrique Martinez, I;Lopez-Herce Cid, J;Zeballos Sarrato, G;Calvo Macias, C;Hernandez-Tejedor, A

10.1016/j.medin.2020.05.004

[Title]: [Recommendations on cardiopulmonary resuscitation in patients with suspected or confirmed SARS-CoV-2 infection (COVID-19). Executive summary]. [Abstract]: The SARS-CoV-2 pandemic has created new scenarios that require modifications to the usual cardiopulmonary resuscitation protocols. The current clinical guidelines on the management of cardiorespiratory arrest do not include recommendations for situations that apply to this context. Therefore, the National Cardiopulmonary Resuscitation Plan of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), in collaboration with the Spanish Group of Pediatric and Neonatal CPR and with the Teaching Life Support in Primary Care program of the Spanish Society of Family and Community Medicine (SEMFyC), have written these recommendations, which are divided into 5 parts that address the main aspects for each healthcare setting. This article consists of an executive summary of them. [Keywords]: covid-19;cardiopulmonary resuscitation;cardiorespiratory arrest;coronavirus;recommendations

Clin Imaging

Preliminary CT findings of coronavirus disease 2019 (COVID-19).

OBJECTIVES: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This paper aims to examine the CT imaging characteristics of COVID-19. METHODS: We evaluated CT images obtained between 10 January 2019 and 16 February 2020 at Taihe Hospital. Scans were conducted 2-6 times per patient and the re-testing interval was 2-7 days. Ninety-five patients with positive SARS-CoV-2 nucleic acid test results were included in this study and we retrospectively analysed their CT imaging characteristics. RESULTS: Ninety-five patients underwent 2-3 SARS-CoV-2 nucleic acid tests and received a definitive diagnosis of COVID-19. Fifty-three were male and 42 were female, and their mean age was 42 +/- 12 years (range: 10 months to 81 years). Sixty-nine patients (72.6%) experienced fever, fatigue, and dry cough, while 15 (15.8%) had poor appetite and fatigue, and 11 (11.6%) had a dry cough and no fever. On CT imaging, early stage patients (n = 53, 55.8%) showed peripheral subpleural ground-glass opacities; these were mainly local patches (22/53, 41.5%), while some lesions were accompanied by interlobular septal thickening. Thirty-four (35.8%) patients were classified in the 'progression stage' based on CT imaging; these patients typically showed lesions in multiple lung segments and lobes (21/3461.8%), and an uneven increase in ground-glass opacity density accompanied by consolidation and grid-like or cord-like shadows(30.5%). Two patients (2.1%) showed a severe presentation on CT. These showed diffuse bilateral lung lesions, mixed ground-glass opacities and consolidation with cord-like interstitial thickening and air bronchograms, entire lung involvement with a "white lung" presentation, and mild pleural effusion. Six patients in remission (6.3%), visible lesion absorption, fibrotic lesions. Based on clinical signs, 71 (74.7%), 22 (23.2%), and 2 (2.1%) patients had mild or moderate, severe, and critical disease, respectively. Within the follow-up period, 93 patients recovered and were discharged, including the 53 early stage patients and 34 progression stage patients. The length of hospitalisation was 7-28 days (mean: 10 +/- 3.5 days). On discharge, lesions were significantly reduced in area and had in many cases completely disappeared, while slight pulmonary fibrosis was present in some patients. One severe stage patient was still hospitalised at the end of the follow-up period and the other severe stage patient died. The overall mortality rate was 1.05%. CONCLUSIONS: Understanding the CT imaging characteristics of COVID-19 is important for early lesion detection, determining the nature of lesions, and assessing disease severity.

Journal Article

Cui, Ning;Zou, Xugong;Xu, Lin

10.1016/j.clinimag.2020.04.042

[Title]: Preliminary CT findings of coronavirus disease 2019 (COVID-19). [Abstract]: OBJECTIVES: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This paper aims to examine the CT imaging characteristics of COVID-19. METHODS: We evaluated CT images obtained between 10 January 2019 and 16 February 2020 at Taihe Hospital. Scans were conducted 2-6 times per patient and the re-testing interval was 2-7 days. Ninety-five patients with positive SARS-CoV-2 nucleic acid test results were included in this study and we retrospectively analysed their CT imaging characteristics. RESULTS: Ninety-five patients underwent 2-3 SARS-CoV-2 nucleic acid tests and received a definitive diagnosis of COVID-19. Fifty-three were male and 42 were female, and their mean age was 42 +/- 12 years (range: 10 months to 81 years). Sixty-nine patients (72.6%) experienced fever, fatigue, and dry cough, while 15 (15.8%) had poor appetite and fatigue, and 11 (11.6%) had a dry cough and no fever. On CT imaging, early stage patients (n = 53, 55.8%) showed peripheral subpleural ground-glass opacities; these were mainly local patches (22/53, 41.5%), while some lesions were accompanied by interlobular septal thickening. Thirty-four (35.8%) patients were classified in the 'progression stage' based on CT imaging; these patients typically showed lesions in multiple lung segments and lobes (21/3461.8%), and an uneven increase in ground-glass opacity density accompanied by consolidation and grid-like or cord-like shadows(30.5%). Two patients (2.1%) showed a severe presentation on CT. These showed diffuse bilateral lung lesions, mixed ground-glass opacities and consolidation with cord-like interstitial thickening and air bronchograms, entire lung involvement with a "white lung" presentation, and mild pleural effusion. Six patients in remission (6.3%), visible lesion absorption, fibrotic lesions. Based on clinical signs, 71 (74.7%), 22 (23.2%), and 2 (2.1%) patients had mild or moderate, severe, and critical disease, respectively. Within the follow-up period, 93 patients recovered and were discharged, including the 53 early stage patients and 34 progression stage patients. The length of hospitalisation was 7-28 days (mean: 10 +/- 3.5 days). On discharge, lesions were significantly reduced in area and had in many cases completely disappeared, while slight pulmonary fibrosis was present in some patients. One severe stage patient was still hospitalised at the end of the follow-up period and the other severe stage patient died. The overall mortality rate was 1.05%. CONCLUSIONS: Understanding the CT imaging characteristics of COVID-19 is important for early lesion detection, determining the nature of lesions, and assessing disease severity. [Keywords]:

Int J Environ Res Public Health

Evaluation of Protection Level, Respiratory Safety, and Practical Aspects of Commercially Available Snorkel Masks as Personal Protection Devices Against Aerosolized Contaminants and SARS-CoV2.

Introduction: The "Severe Acute Respiratory Syndrome Coronavirus 2'' (SARS-CoV2) pandemic has led to a worldwide shortage of personal protection devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO2) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A 'fit' test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO2 and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO2 was noted, remaining within physiological limits. 3D printed adaptors are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts, and choice of filter are important.

sars-cov2;personal protection devices;safety test;snorkel masks

Evaluation Study;Journal Article

Germonpre, Peter;Van Rompaey, Dirk;Balestra, Costantino

10.3390/ijerph17124347

[Title]: Evaluation of Protection Level, Respiratory Safety, and Practical Aspects of Commercially Available Snorkel Masks as Personal Protection Devices Against Aerosolized Contaminants and SARS-CoV2. [Abstract]: Introduction: The "Severe Acute Respiratory Syndrome Coronavirus 2'' (SARS-CoV2) pandemic has led to a worldwide shortage of personal protection devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO2) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A 'fit' test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO2 and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO2 was noted, remaining within physiological limits. 3D printed adaptors are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts, and choice of filter are important. [Keywords]: sars-cov2;personal protection devices;safety test;snorkel masks

Ann Palliat Med

Xuebijing injection in the treatment of COVID-19: a retrospective case-control study.

BACKGROUND: Neither a vaccine nor specific therapeutic drugs against 2019 novel coronavirus have been developed. Some studies have shown that Xuebijing injection (XBJ) can exert an anti-inflammatory effect by inhibiting the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and other cytokines. This study aimed to investigate the effect of XBJ on coronavirus disease 2019 (COVID-19) and its effects on IL-6 and tumor necrosis alpha TNF-alpha. METHODS: A total of 42 patients, who were diagnosed with COVID-19 and treated with XBJ combined with routine treatment at Chongqing University Three Gorges Hospital between January 20, 2020, and March 11, 2020, were selected as the observation group. A control group comprising 16 patients who received routine treatment was also established, and cases were matched from the observation group on a 1:1 basis according to age, comorbidities, and mild and severe disease. The clinical symptoms, laboratory test indexes, and changes in computed tomography (CT) scans of patients in the two groups were observed at the time of admission and 7 days after treatment, and the time taken for the patients to produce a negative nucleic acid test was also recorded. RESULTS: There were no significant differences in baseline data between the two groups. After treatment, there were significant improvements in IL-6 levels and body temperature in the observation group as compared with the control group. Particularly in severe patients, the reduction in body temperature in the observation group was greater than that in the control group (P<0.05). A higher number of patients in the observation group showed improved CT imaging results compared with the control group, and the time taken to produce a negative nucleic acid test was shorter in the observation group than in the control group; however, the differences were not statistically significant (P>0.05). Furthermore, there were no significant differences in TNF-alpha and IL-10 between the two groups. CONCLUSIONS: The results of this study suggest that routine treatment combined with XBJ can better improve the clinical outcomes of COVID-19 patients.

xuebijing injection;coronavirus disease 2019 (covid-19);effect;interleukin 6 (il-6)

Journal Article

Guo, Hu;Zheng, Jiangyuan;Huang, Gu;Xiang, Yi;Lang, Chunhui;Li, Boqun;Huang, Daoqiu;Sun, Qiuyan;Luo, Yaling;Zhang, Yulian;Huang, Liang;Fang, Wei;Zheng, Yu;Wan, Suxin

10.21037/apm-20-1478

[Title]: Xuebijing injection in the treatment of COVID-19: a retrospective case-control study. [Abstract]: BACKGROUND: Neither a vaccine nor specific therapeutic drugs against 2019 novel coronavirus have been developed. Some studies have shown that Xuebijing injection (XBJ) can exert an anti-inflammatory effect by inhibiting the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and other cytokines. This study aimed to investigate the effect of XBJ on coronavirus disease 2019 (COVID-19) and its effects on IL-6 and tumor necrosis alpha TNF-alpha. METHODS: A total of 42 patients, who were diagnosed with COVID-19 and treated with XBJ combined with routine treatment at Chongqing University Three Gorges Hospital between January 20, 2020, and March 11, 2020, were selected as the observation group. A control group comprising 16 patients who received routine treatment was also established, and cases were matched from the observation group on a 1:1 basis according to age, comorbidities, and mild and severe disease. The clinical symptoms, laboratory test indexes, and changes in computed tomography (CT) scans of patients in the two groups were observed at the time of admission and 7 days after treatment, and the time taken for the patients to produce a negative nucleic acid test was also recorded. RESULTS: There were no significant differences in baseline data between the two groups. After treatment, there were significant improvements in IL-6 levels and body temperature in the observation group as compared with the control group. Particularly in severe patients, the reduction in body temperature in the observation group was greater than that in the control group (P<0.05). A higher number of patients in the observation group showed improved CT imaging results compared with the control group, and the time taken to produce a negative nucleic acid test was shorter in the observation group than in the control group; however, the differences were not statistically significant (P>0.05). Furthermore, there were no significant differences in TNF-alpha and IL-10 between the two groups. CONCLUSIONS: The results of this study suggest that routine treatment combined with XBJ can better improve the clinical outcomes of COVID-19 patients. [Keywords]: xuebijing injection;coronavirus disease 2019 (covid-19);effect;interleukin 6 (il-6)

J Neurol Sci

Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced 'PANIC' attack.

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered 'PANIC Attack'. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health.

ace-2 receptor;adaptive immunity;alveoli;covid-19;complement;cytokine;gas exchange;innate immunity;methotrexate;sars-cov-2;spike protein

Journal Article;Review

Frohman, Elliot M;Villemarette-Pittman, Nicole R;Cruz, Roberto Alejandro;Longmuir, Reid;Rowe, Vernon;Rowe, Elizabeth S;Varkey, Thomas C;Steinman, Lawrence;Zamvil, Scott S;Frohman, Teresa C

10.1016/j.jns.2020.116935

[Title]: Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced 'PANIC' attack. [Abstract]: Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered 'PANIC Attack'. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health. [Keywords]: ace-2 receptor;adaptive immunity;alveoli;covid-19;complement;cytokine;gas exchange;innate immunity;methotrexate;sars-cov-2;spike protein

J Peripher Nerv Syst

Guillain-Barre syndrome during SARS-CoV-2 pandemic: A case report and review of recent literature.

Acute demyelinating inflammatory polyneuropathy (AIDP) is the most common type of Guillain-Barre syndrome (GBS) in Europe, following several viral and bacterial infections. Data on AIDP-patients associated with SARS-CoV-2 (coronavirus-2) infection are scarce. We describe the case of a 54-years-old Caucasian female patient with typical clinical and electrophysiological manifestations of AIDP, who was reported positive with PCR for SARS-CoV-2, 3 weeks prior to onset of the neurological symptoms. She did not experience a preceding fever or respiratory symptoms, but a transient loss of smell and taste. At the admission to our neurological department, a progressive proximally pronounced paraparesis, areflexia, and sensory loss with tingling of all extremities were found, which began 10 days before. The modified Erasmus Giullain-Barre Syndrome outcome score (mEGOS) was 3/9 at admission and 1/12 at day 7 of hospitalization. The electrophysiological assessment proved a segmental demyelinating polyneuropathy and cerebrospinal fluid examination showed an albuminocytologic dissociation. The neurological symptoms improved significantly during treatment with immunoglobulins. Our case draws attention to the occurrence of GBS also in patients with COVID-19 (coronavirus disease 2019), who did not experience respiratory or general symptoms. It emphasizes that SARS-CoV-2 induces immunological processes, regardless from the lack of prodromic symptoms. However, it is likely that there is a connection between the severity of the respiratory syndrome and further neurological consequences.

covid-19;guillain-barre syndrome;sars-cov2

Case Reports;Journal Article;Review

Scheidl, Erika;Canseco, Daniel Diez;Hadji-Naumov, Aleksandar;Bereznai, Benjamin

10.1111/jns.12382

[Title]: Guillain-Barre syndrome during SARS-CoV-2 pandemic: A case report and review of recent literature. [Abstract]: Acute demyelinating inflammatory polyneuropathy (AIDP) is the most common type of Guillain-Barre syndrome (GBS) in Europe, following several viral and bacterial infections. Data on AIDP-patients associated with SARS-CoV-2 (coronavirus-2) infection are scarce. We describe the case of a 54-years-old Caucasian female patient with typical clinical and electrophysiological manifestations of AIDP, who was reported positive with PCR for SARS-CoV-2, 3 weeks prior to onset of the neurological symptoms. She did not experience a preceding fever or respiratory symptoms, but a transient loss of smell and taste. At the admission to our neurological department, a progressive proximally pronounced paraparesis, areflexia, and sensory loss with tingling of all extremities were found, which began 10 days before. The modified Erasmus Giullain-Barre Syndrome outcome score (mEGOS) was 3/9 at admission and 1/12 at day 7 of hospitalization. The electrophysiological assessment proved a segmental demyelinating polyneuropathy and cerebrospinal fluid examination showed an albuminocytologic dissociation. The neurological symptoms improved significantly during treatment with immunoglobulins. Our case draws attention to the occurrence of GBS also in patients with COVID-19 (coronavirus disease 2019), who did not experience respiratory or general symptoms. It emphasizes that SARS-CoV-2 induces immunological processes, regardless from the lack of prodromic symptoms. However, it is likely that there is a connection between the severity of the respiratory syndrome and further neurological consequences. [Keywords]: covid-19;guillain-barre syndrome;sars-cov2

Mil Med Res

The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status.

An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to beta-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

clinical characteristics;coronavirus disease 2019 (covid-19);origin;sars-cov-2;therapy;transmission

Journal Article;Research Support, Non-U.S. Gov't;Review

Guo, Yan-Rong;Cao, Qing-Dong;Hong, Zhong-Si;Tan, Yuan-Yang;Chen, Shou-Deng;Jin, Hong-Jun;Tan, Kai-Sen;Wang, De-Yun;Yan, Yan

10.1186/s40779-020-00240-0

[Title]: The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. [Abstract]: An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to beta-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus. [Keywords]: clinical characteristics;coronavirus disease 2019 (covid-19);origin;sars-cov-2;therapy;transmission

Lancet

Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. METHODS: In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. FINDINGS: The median age of our cohort was 73.5 years (range 42-84; IQR 67.5-77.25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. INTERPRETATION: The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. FUNDING: None.

Journal Article

Bradley, Benjamin T;Maioli, Heather;Johnston, Robert;Chaudhry, Irfan;Fink, Susan L;Xu, Haodong;Najafian, Behzad;Deutsch, Gail;Lacy, J Matthew;Williams, Timothy;Yarid, Nicole;Marshall, Desiree A

10.1016/S0140-6736(20)31305-2

[Title]: Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series. [Abstract]: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. METHODS: In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. FINDINGS: The median age of our cohort was 73.5 years (range 42-84; IQR 67.5-77.25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. INTERPRETATION: The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. FUNDING: None. [Keywords]:

Emerg Microbes Infect

Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2.

Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.

covid-19;sars;sars-cov-2;antibody;cross-neutralization

Letter

Anderson, Danielle E;Tan, Chee Wah;Chia, Wan Ni;Young, Barnaby E;Linster, Martin;Low, JennyG H;Tan, Yee-Joo;Chen, Mark I-C;Smith, Gavin J D;Leo, Yee Sin;Lye, David C;Wang, Lin-Fa

10.1080/22221751.2020.1761267

[Title]: Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2. [Abstract]: Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy. [Keywords]: covid-19;sars;sars-cov-2;antibody;cross-neutralization

Clin Imaging

Magnetic resonance imaging features of coronavirus disease 2019 (COVID-19) pneumonia: The first preliminary case series.

RATIONALE AND OBJECTIVES: There is a rising onus on understanding the common features of COVID-19 pneumonia on different imaging modalities. In this study, we aimed to review and depict the common MRI features of COVID-19 pneumonia in our laboratory confirmed case series, the first comprehensive reported cohort in the literature. MATERIALS AND METHODS: Upon IRB approval, eight laboratory confirmed COVID-19 patients who presented to our outpatient imaging clinic underwent chest CT and, once various features of COVID-19 pneumonia were identified, a dedicated multisequence chest MRI was performed on the same day with an institutional protocol. Demographic data and the morphology, laterality and location of the lesions were recorded for each case. RESULTS: Five males and three females with the mean age of 40.63 +/- 12.64 years old were present in this case series. Five cases had typical CT features with ground glass opacities and consolidations, readily visible on different MRI sequences. Three cases had indeterminate or atypical features which were also easily seen on MRI. The comprehensive review of MRI features for each case and representative images have been illustrated. CONCLUSION: Becoming familiar with typical findings of COVID-19 pneumonia in MRI is crucial for every radiologist. Although MRI is not the modality of choice for evaluation of pulmonary opacities, it has similar capabilities in detection of COVID-19 pneumonia when compared to chest CT.

covid-19 pneumonia;coronavirus;magnetic resonance imaging

Journal Article;Review

Torkian, Pooya;Rajebi, Hamid;Zamani, Taraneh;Ramezani, Naghi;Kiani, Pejman;Akhlaghpoor, Shahram

10.1016/j.clinimag.2020.09.002

[Title]: Magnetic resonance imaging features of coronavirus disease 2019 (COVID-19) pneumonia: The first preliminary case series. [Abstract]: RATIONALE AND OBJECTIVES: There is a rising onus on understanding the common features of COVID-19 pneumonia on different imaging modalities. In this study, we aimed to review and depict the common MRI features of COVID-19 pneumonia in our laboratory confirmed case series, the first comprehensive reported cohort in the literature. MATERIALS AND METHODS: Upon IRB approval, eight laboratory confirmed COVID-19 patients who presented to our outpatient imaging clinic underwent chest CT and, once various features of COVID-19 pneumonia were identified, a dedicated multisequence chest MRI was performed on the same day with an institutional protocol. Demographic data and the morphology, laterality and location of the lesions were recorded for each case. RESULTS: Five males and three females with the mean age of 40.63 +/- 12.64 years old were present in this case series. Five cases had typical CT features with ground glass opacities and consolidations, readily visible on different MRI sequences. Three cases had indeterminate or atypical features which were also easily seen on MRI. The comprehensive review of MRI features for each case and representative images have been illustrated. CONCLUSION: Becoming familiar with typical findings of COVID-19 pneumonia in MRI is crucial for every radiologist. Although MRI is not the modality of choice for evaluation of pulmonary opacities, it has similar capabilities in detection of COVID-19 pneumonia when compared to chest CT. [Keywords]: covid-19 pneumonia;coronavirus;magnetic resonance imaging

Infect Control Hosp Epidemiol

Navigating hospitals safely through the COVID-19 epidemic tide: predicting case load for adjusting bed capacity.

BACKGROUND: The pressures exerted by the pandemic of COVID-19 pose an unprecedented demand on health care services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. We here describe methods used by a university hospital to forecast caseloads and time to peak incidence. METHODS: We developed a set of models to forecast incidence among the hospital catchment population and describe the COVID-19 patient hospital care-path. The first forecast utilized data from antecedent allopatric epidemics and parameterized the care path model according to expert opinion (static model). Once sufficient local data were available, trends for the time dependent effective reproduction number were fitted and the care-path was re-parameterized using hazards for real patient admission, referrals, and discharge (dynamic model). RESULTS: The static model, deployed before the epidemic, exaggerated the bed occupancy (general wards 116 forecasted vs 66 observed, ICU 47 forecasted vs 34 observed) and predicted the peak too late (general ward forecast April 9, observed April 8, ICU forecast April 19, observed April 8). After April 5, the dynamic model could be run daily and precision improved with increasing availability of empirical local data. CONCLUSIONS: The models provided data-based guidance in the preparation and allocation of critical resources of a university hospital well in advance of the epidemic surge, despite overestimating the service demand. Overestimates should resolve when population contact pattern before and during restrictions can be taken into account, but for now they may provide an acceptable safety margin for preparing during times of uncertainty.

Journal Article

Donker, Tjibbe;Burkin, Fabian;Wolkewitz, Martin;Haverkamp, Christian;Christoffel, Dominic;Kappert, Oliver;Hammer, Thorsten;Busch, Hans-Jorg;Biever, Paul;Kalbhenn, Johannes;Burkle, Hartmut;Kern, Winfried;Wenz, Frederik;Grundmann, Hajo

10.1017/ice.2020.464

[Title]: Navigating hospitals safely through the COVID-19 epidemic tide: predicting case load for adjusting bed capacity. [Abstract]: BACKGROUND: The pressures exerted by the pandemic of COVID-19 pose an unprecedented demand on health care services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. We here describe methods used by a university hospital to forecast caseloads and time to peak incidence. METHODS: We developed a set of models to forecast incidence among the hospital catchment population and describe the COVID-19 patient hospital care-path. The first forecast utilized data from antecedent allopatric epidemics and parameterized the care path model according to expert opinion (static model). Once sufficient local data were available, trends for the time dependent effective reproduction number were fitted and the care-path was re-parameterized using hazards for real patient admission, referrals, and discharge (dynamic model). RESULTS: The static model, deployed before the epidemic, exaggerated the bed occupancy (general wards 116 forecasted vs 66 observed, ICU 47 forecasted vs 34 observed) and predicted the peak too late (general ward forecast April 9, observed April 8, ICU forecast April 19, observed April 8). After April 5, the dynamic model could be run daily and precision improved with increasing availability of empirical local data. CONCLUSIONS: The models provided data-based guidance in the preparation and allocation of critical resources of a university hospital well in advance of the epidemic surge, despite overestimating the service demand. Overestimates should resolve when population contact pattern before and during restrictions can be taken into account, but for now they may provide an acceptable safety margin for preparing during times of uncertainty. [Keywords]:

Fetal Pediatr Pathol

Histopathology of Third Trimester Placenta from SARS-CoV-2-Positive Women.

BACKGROUND: This study aims to investigate whether maternal SARS-CoV-2 status affects placental pathology. Methods: A retrospective case-control study was conducted by reviewing charts and slides of placentas delivered between April 1 to July 24, 2020. Clinical history of "COVID-19" was searched in Pathology Database (CoPath). Controls were matched with SARS-CoV-2-negative women with singleton deliveries in the 3(rd)-trimester. Pathological features were extracted from placental pathology reports. Results: Twenty-one 3(rd) trimester placentas from SARS-CoV-2-positive women were identified and compared to 20 placentas from SARS-CoV-2-negative women. There were no significant differences in individual or group gross or microscopic pathological features. Within the SARS-CoV-2+ group, there are no differences between symptomatic and asymptomatic women. Conclusion: Placentas from SARS-CoV-2-positive women do not demonstrate a specific pathological pattern. Pregnancy complicated with COVID-19 during the 3(rd) trimester does not have a demonstrable effect on placental structure and pathology.

covid-19;pathology;placenta;third trimester

Journal Article

He, Mai;Skaria, Priya;Kreutz, Kasey;Chen, Ling;Hagemann, Ian S;Carter, Ebony B;Mysorekar, Indira U;Nelson, D Michael;Pfeifer, John;Dehner, Louis P

10.1080/15513815.2020.1828517

[Title]: Histopathology of Third Trimester Placenta from SARS-CoV-2-Positive Women. [Abstract]: BACKGROUND: This study aims to investigate whether maternal SARS-CoV-2 status affects placental pathology. Methods: A retrospective case-control study was conducted by reviewing charts and slides of placentas delivered between April 1 to July 24, 2020. Clinical history of "COVID-19" was searched in Pathology Database (CoPath). Controls were matched with SARS-CoV-2-negative women with singleton deliveries in the 3(rd)-trimester. Pathological features were extracted from placental pathology reports. Results: Twenty-one 3(rd) trimester placentas from SARS-CoV-2-positive women were identified and compared to 20 placentas from SARS-CoV-2-negative women. There were no significant differences in individual or group gross or microscopic pathological features. Within the SARS-CoV-2+ group, there are no differences between symptomatic and asymptomatic women. Conclusion: Placentas from SARS-CoV-2-positive women do not demonstrate a specific pathological pattern. Pregnancy complicated with COVID-19 during the 3(rd) trimester does not have a demonstrable effect on placental structure and pathology. [Keywords]: covid-19;pathology;placenta;third trimester

Case Rep Crit Care

Critical Care Management for Novel 2019 SARS-CoV-2 and HCoV-NL63 Coinfection in a Young Immunocompromised Patient: A Chicago Experience.

Background: SARS-CoV-2 is a newly emerged virus that has spread rapidly, exhibiting tremendous morbidity and mortality. Some potential pharmaceutical targets have been identified but are still lacking proper validation. Case Presentation. We describe the case of a young, immunosuppressed and critically ill patient with previous Influenza B infection, requiring extracorporeal membrane oxygenation, which was then followed, in the succeeding months, by SARS-CoV-2 infection complicated by severe adult respiratory distress syndrome. Her clinical course exhibited complications, including pulmonary embolism, acute kidney injury, pneumothorax, pneumomediastinum, multiple cardiac arrests, and eventually death. Conclusion: Coinfection with other respiratory pathogens and opportunistic infections are possible.

Case Reports

Sanchez-Nadales, Alejandro;Treminio-Quezada, Miguel;Abad, Hasan;Navarro-Motta, Jessica;Contreras-Chavez, Pamela;Kachru, Anil;Chu, Chae

10.1155/2020/8877641

[Title]: Critical Care Management for Novel 2019 SARS-CoV-2 and HCoV-NL63 Coinfection in a Young Immunocompromised Patient: A Chicago Experience. [Abstract]: Background: SARS-CoV-2 is a newly emerged virus that has spread rapidly, exhibiting tremendous morbidity and mortality. Some potential pharmaceutical targets have been identified but are still lacking proper validation. Case Presentation. We describe the case of a young, immunosuppressed and critically ill patient with previous Influenza B infection, requiring extracorporeal membrane oxygenation, which was then followed, in the succeeding months, by SARS-CoV-2 infection complicated by severe adult respiratory distress syndrome. Her clinical course exhibited complications, including pulmonary embolism, acute kidney injury, pneumothorax, pneumomediastinum, multiple cardiac arrests, and eventually death. Conclusion: Coinfection with other respiratory pathogens and opportunistic infections are possible. [Keywords]:

Infect Genet Evol

Genome based evolutionary lineage of SARS-CoV-2 towards the development of novel chimeric vaccine.

The present study aimed to predict a novel chimeric vaccine by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein, membrane protein, envelope protein and nucleocapsid protein were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and normal mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. However, the in vivo and in vitro validation of suggested vaccine molecule might be ensured with wet lab trials using model animals for the implementation of the presented data.

covid-19;chimeric vaccine;evolutionary relationship;molecular docking;normal mode analysis;restriction cloning;sars-cov-2

Journal Article

Akhand, Mst Rubaiat Nazneen;Azim, Kazi Faizul;Hoque, Syeda Farjana;Moli, Mahmuda Akther;Joy, Bijit Das;Akter, Hafsa;Afif, Ibrahim Khalil;Ahmed, Nadim;Hasan, Mahmudul

10.1016/j.meegid.2020.104517

[Title]: Genome based evolutionary lineage of SARS-CoV-2 towards the development of novel chimeric vaccine. [Abstract]: The present study aimed to predict a novel chimeric vaccine by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein, membrane protein, envelope protein and nucleocapsid protein were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and normal mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. However, the in vivo and in vitro validation of suggested vaccine molecule might be ensured with wet lab trials using model animals for the implementation of the presented data. [Keywords]: covid-19;chimeric vaccine;evolutionary relationship;molecular docking;normal mode analysis;restriction cloning;sars-cov-2

Matter

Reducing False Negatives in COVID-19 Testing by Using Microneedle-Based Oropharyngeal Swabs.

Coronavirus disease 2019 (COVID-19) has become a severe threat to human health worldwide. Early etiological diagnosis plays a critical role in controlling COVID-19 pandemic. However, etiological diagnosis has been largely compromised by high "false-negative" rates of viral nucleic acid testing, resulting from limited sampling efficiency using conventional oropharyngeal swabs. Here, we engineer regular swabs by using a microneedle (MN) patch to significantly improve the quality and quantity of virus collection. The combination of MNs with different crosslinking levels endows the patches with dual capability of mucus penetration and virus extraction. Moreover, the antibody (Ab) against viral spike protein was integrated into the patch, conferring MNs with an active virus capture potential. By taking advantage of the biological and engineered species, we believe that the designed MN/Ab swabs could serve as a promising tool to improve current sampling efficiency with fewer false negatives, contributing to the containment of the COVID-19 pandemic.

map6: development

Journal Article

Chen, Wei;Cai, Bo;Geng, Zhi;Chen, Fenghua;Wang, Zheng;Wang, Lin;Chen, Xiaoyuan

10.1016/j.matt.2020.09.021

[Title]: Reducing False Negatives in COVID-19 Testing by Using Microneedle-Based Oropharyngeal Swabs. [Abstract]: Coronavirus disease 2019 (COVID-19) has become a severe threat to human health worldwide. Early etiological diagnosis plays a critical role in controlling COVID-19 pandemic. However, etiological diagnosis has been largely compromised by high "false-negative" rates of viral nucleic acid testing, resulting from limited sampling efficiency using conventional oropharyngeal swabs. Here, we engineer regular swabs by using a microneedle (MN) patch to significantly improve the quality and quantity of virus collection. The combination of MNs with different crosslinking levels endows the patches with dual capability of mucus penetration and virus extraction. Moreover, the antibody (Ab) against viral spike protein was integrated into the patch, conferring MNs with an active virus capture potential. By taking advantage of the biological and engineered species, we believe that the designed MN/Ab swabs could serve as a promising tool to improve current sampling efficiency with fewer false negatives, contributing to the containment of the COVID-19 pandemic. [Keywords]: map6: development

Life Sci

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis.

AIMS: The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19. MATERIALS AND METHODS: The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein-protein interaction (PPI) and chemo-protein interaction (CPI) networks were constructed and combined to develop an interactome model of PPI-CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. KEY FINDINGS: A total of 120 DEGs and 65 drugs were identified. The PPI-CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. SIGNIFICANCE: The present study reveals that between chloroquine and melatonin, melatonin appears to be more promising repurposed drug against MMP9 for better immunocompromisation in COVID-19.

covid-19;chloroquine;coronavirus;mmp9;melatonin;ppi-cpi network;sars-cov-2

Journal Article;Meta-Analysis

Hazra, Suvojit;Chaudhuri, Alok Ghosh;Tiwary, Basant K;Chakrabarti, Nilkanta

10.1016/j.lfs.2020.118096

[Title]: Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis. [Abstract]: AIMS: The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19. MATERIALS AND METHODS: The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein-protein interaction (PPI) and chemo-protein interaction (CPI) networks were constructed and combined to develop an interactome model of PPI-CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. KEY FINDINGS: A total of 120 DEGs and 65 drugs were identified. The PPI-CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. SIGNIFICANCE: The present study reveals that between chloroquine and melatonin, melatonin appears to be more promising repurposed drug against MMP9 for better immunocompromisation in COVID-19. [Keywords]: covid-19;chloroquine;coronavirus;mmp9;melatonin;ppi-cpi network;sars-cov-2

PLoS One

Ischemic stroke in COVID-19: An urgent need for early identification and management.

OBJECTIVE: In the setting of the Coronavirus Disease 2019 (COVID-19) global pandemic caused by SARS-CoV-2, a potential association of this disease with stroke has been suggested. We aimed to describe the characteristics of patients who were admitted with COVID-19 and had an acute ischemic stroke (AIS). METHODS: This is a case series of PCR-confirmed COVID-19 patients with ischemic stroke admitted to an academic health system in metropolitan Atlanta, Georgia (USA) between March 24th, 2020 and July 17th, 2020. Demographic, clinical, and radiographic characteristics were described. RESULTS: Of 396 ischemic stroke patients admitted during this study period, 13 (2.5%) were also diagnosed with COVID-19. The mean age of patients was 61.6 +/- 10.8 years, 10 (76.9%) male, 8 (61.5%) were Black Americans, mean time from last normal was 4.97 +/- 5.1 days, and only one received acute reperfusion therapy. All 13 patients had at least one stroke-associated co-morbidity. The predominant pattern of ischemic stroke was embolic with 4 explained by atrial fibrillation. COVID-19 patients had a significantly higher rate of cryptogenic stroke than non-COVID-19 patients during the study period (69% vs 17%, p = 0.0001). CONCLUSIONS: In our case series, ischemic stroke affected COVID-19 patients with traditional stroke risk factors at an age typically seen in non-COVID populations, and mainly affecting males and Black Americans. We observed a predominantly embolic pattern of stroke with a higher than expected rate of cryptogenic strokes, a prolonged median time to presentation and symptom recognition limiting the use of acute reperfusion treatments. These results highlight the need for increased community awareness, early identification, and management of AIS in COVID-19 patients.

Journal Article

Jillella, Dinesh V;Janocko, Nicholas J;Nahab, Fadi;Benameur, Karima;Greene, James G;Wright, Wendy L;Obideen, Mahmoud;Rangaraju, Srikant

10.1371/journal.pone.0239443

[Title]: Ischemic stroke in COVID-19: An urgent need for early identification and management. [Abstract]: OBJECTIVE: In the setting of the Coronavirus Disease 2019 (COVID-19) global pandemic caused by SARS-CoV-2, a potential association of this disease with stroke has been suggested. We aimed to describe the characteristics of patients who were admitted with COVID-19 and had an acute ischemic stroke (AIS). METHODS: This is a case series of PCR-confirmed COVID-19 patients with ischemic stroke admitted to an academic health system in metropolitan Atlanta, Georgia (USA) between March 24th, 2020 and July 17th, 2020. Demographic, clinical, and radiographic characteristics were described. RESULTS: Of 396 ischemic stroke patients admitted during this study period, 13 (2.5%) were also diagnosed with COVID-19. The mean age of patients was 61.6 +/- 10.8 years, 10 (76.9%) male, 8 (61.5%) were Black Americans, mean time from last normal was 4.97 +/- 5.1 days, and only one received acute reperfusion therapy. All 13 patients had at least one stroke-associated co-morbidity. The predominant pattern of ischemic stroke was embolic with 4 explained by atrial fibrillation. COVID-19 patients had a significantly higher rate of cryptogenic stroke than non-COVID-19 patients during the study period (69% vs 17%, p = 0.0001). CONCLUSIONS: In our case series, ischemic stroke affected COVID-19 patients with traditional stroke risk factors at an age typically seen in non-COVID populations, and mainly affecting males and Black Americans. We observed a predominantly embolic pattern of stroke with a higher than expected rate of cryptogenic strokes, a prolonged median time to presentation and symptom recognition limiting the use of acute reperfusion treatments. These results highlight the need for increased community awareness, early identification, and management of AIS in COVID-19 patients. [Keywords]:

Front Physiol

COVID-19 Sepsis and Microcirculation Dysfunction.

The spreading of Coronavirus (SARS-CoV-2) pandemic, known as COVID-19, has caused a great number of fatalities all around the World. Up to date (2020 May 6) in Italy we had more than 28,000 deaths, while there were more than 205.000 infected. The majority of patients affected by COVID-19 complained only slight symptoms: fatigue, myalgia or cough, but more than 15% of Chinese patients progressed into severe complications, with acute respiratory distress syndrome (ARDS), needing intensive treatment. We tried to summarize data reported in the last months from several Countries, highlighting that COVID-19 was characterized by cytokine storm (CS) and endothelial dysfunction in severely ill patients, where the progression of the disease was fast and fatal. Endothelial dysfunction was the fundamental mechanism triggering a pro-coagulant state, finally evolving into intravascular disseminated coagulation, causing embolization of several organs and consequent multiorgan failure (MOF). The Italian Society of Clinical Hemorheology and Microcirculation was aimed to highlight the role of microcirculatory dysfunction in the pathogenetic mechanisms of COVID-19 during the spreading of the biggest challenges to the World Health.

covid-19;angiotensin ii;endothelial cells;microcirculation;thromboxane (txb2)

Journal Article;Review

Colantuoni, Antonio;Martini, Romeo;Caprari, Patrizia;Ballestri, Marco;Capecchi, Pier Leopoldo;Gnasso, Agostino;Lo Presti, Rosalia;Marcoccia, Antonella;Rossi, Marco;Caimi, Gregorio

10.3389/fphys.2020.00747

[Title]: COVID-19 Sepsis and Microcirculation Dysfunction. [Abstract]: The spreading of Coronavirus (SARS-CoV-2) pandemic, known as COVID-19, has caused a great number of fatalities all around the World. Up to date (2020 May 6) in Italy we had more than 28,000 deaths, while there were more than 205.000 infected. The majority of patients affected by COVID-19 complained only slight symptoms: fatigue, myalgia or cough, but more than 15% of Chinese patients progressed into severe complications, with acute respiratory distress syndrome (ARDS), needing intensive treatment. We tried to summarize data reported in the last months from several Countries, highlighting that COVID-19 was characterized by cytokine storm (CS) and endothelial dysfunction in severely ill patients, where the progression of the disease was fast and fatal. Endothelial dysfunction was the fundamental mechanism triggering a pro-coagulant state, finally evolving into intravascular disseminated coagulation, causing embolization of several organs and consequent multiorgan failure (MOF). The Italian Society of Clinical Hemorheology and Microcirculation was aimed to highlight the role of microcirculatory dysfunction in the pathogenetic mechanisms of COVID-19 during the spreading of the biggest challenges to the World Health. [Keywords]: covid-19;angiotensin ii;endothelial cells;microcirculation;thromboxane (txb2)

Clin Ophthalmol

The Paradigm Shift of Ophthalmology in the COVID-19 Era.

Objective: To describe how a fixed regimen of intravitreal injections (IVI) was helpful to continue activity during the COVID-19 outbreak and lockdown and to address basic conditions to resume activity. Methods: A fixed regimen of IVI was conceived to significantly reduce the number of visits while keeping a number of injections related to the best outcomes. We retrospectively collected data of surgeries performed in 2019 and in the first seven months of 2020 and from OCTs in the first semester of 2020. Results: IVI per month, from January to July 2020, were 304, 291, 256, 204, 276, 297 and 322, respectively. Phacoemulsification surgeries in the same period were 397, 408, 171, 0, 304, 391 and 389. Posterior vitrectomies were 23, 21, 17, 10, 21, 28 and 25. Laser sessions were 44, 26, 33, 17, 23 and 33, respectively. OCTs dropped from a mean of 25.7 per day in the first half of March 2020 to 5.8 per day in the second half of March. A mean of 6.5 OCTs per day was made in April, rising to 19.1 in May and 39.5 in June. Conclusion: It was possible to keep the ophthalmological activity during the pandemic outbreak due to the existence of a pre-scheduled fixed regimen for IVI and to the availability of personal protective equipment. The air-borne nature of the peril we are facing addresses the need to evaluate the physical conditions of health facilities, including ventilation, size of waiting and consult rooms and the need to avoid elevators.

covid-19;rt-pcr testing;sars-cov-2;fixed regimen;intra-vitreal injections;resume activity

Journal Article

Campos, Antonio;Oliveira, Nuno;Martins, Joana;Arruda, Henrique;Sousa, Joao

10.2147/OPTH.S267427

[Title]: The Paradigm Shift of Ophthalmology in the COVID-19 Era. [Abstract]: Objective: To describe how a fixed regimen of intravitreal injections (IVI) was helpful to continue activity during the COVID-19 outbreak and lockdown and to address basic conditions to resume activity. Methods: A fixed regimen of IVI was conceived to significantly reduce the number of visits while keeping a number of injections related to the best outcomes. We retrospectively collected data of surgeries performed in 2019 and in the first seven months of 2020 and from OCTs in the first semester of 2020. Results: IVI per month, from January to July 2020, were 304, 291, 256, 204, 276, 297 and 322, respectively. Phacoemulsification surgeries in the same period were 397, 408, 171, 0, 304, 391 and 389. Posterior vitrectomies were 23, 21, 17, 10, 21, 28 and 25. Laser sessions were 44, 26, 33, 17, 23 and 33, respectively. OCTs dropped from a mean of 25.7 per day in the first half of March 2020 to 5.8 per day in the second half of March. A mean of 6.5 OCTs per day was made in April, rising to 19.1 in May and 39.5 in June. Conclusion: It was possible to keep the ophthalmological activity during the pandemic outbreak due to the existence of a pre-scheduled fixed regimen for IVI and to the availability of personal protective equipment. The air-borne nature of the peril we are facing addresses the need to evaluate the physical conditions of health facilities, including ventilation, size of waiting and consult rooms and the need to avoid elevators. [Keywords]: covid-19;rt-pcr testing;sars-cov-2;fixed regimen;intra-vitreal injections;resume activity

J Infect Chemother

Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship.

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.

covid-19;coronavirus;diamond princess cruise ship;outbreak;sars-cov-2

Journal Article

Kato, Hideaki;Shimizu, Hiroyuki;Shibue, Yasushi;Hosoda, Tomohiro;Iwabuchi, Keisuke;Nagamine, Kotaro;Saito, Hiroki;Sawada, Reimin;Oishi, Takayuki;Tsukiji, Jun;Fujita, Hiroyuki;Furuya, Ryosuke;Masuda, Makoto;Akasaka, Osamu;Ikeda, Yu;Sakamoto, Mitsuo;Sakai, Kazuya;Uchiyama, Munehito;Watanabe, Hiroki;Yamaguchi, Nobuhiro;Higa, Ryoko;Sasaki, Akiko;Tanaka, Katsuaki;Toyoda, Yukitoshi;Hamanaka, Shinsuke;Miyazawa, Naoki;Shimizu, Atsuko;Fukase, Fumie;Iwai, Shunsuke;Komase, Yuko;Kawasaki, Tsutomu;Nagata, Isao;Nakayama, Yusuke;Takei, Tetsuhiro;Kimura, Katsuo;Kunisaki, Reiko;Kudo, Makoto;Takeuchi, Ichiro;Nakajima, Hideaki

10.1016/j.jiac.2020.05.005

[Title]: Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship. [Abstract]: We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients. [Keywords]: covid-19;coronavirus;diamond princess cruise ship;outbreak;sars-cov-2

Int J MCH AIDS

COVID-19 Pandemic in Nigeria: Palliative Measures and the Politics of Vulnerability.

In a bid to slow the rate of spread of the virus, the Federal Government of Nigeria, on several occasions, imposed targeted lockdown measures in areas with rapid increase of Covid-19 cases. The states in which the federal government imposed the targeted lockdown included Lagos, Ogun, and the Federal Capital Territory in Abuja. Some States in the country imposed partial lockdown and closure of interstate boarders. Curfews have also been introduced in all the states nationwide. To alleviate the effects of the lockdown, the Federal Government of Nigeria rolled out palliative measures for targeted groups. However, lamentations have trailed the distribution of government palliatives by the masses. Citizens allege that the process of distribution of palliatives had been politicized.

corona virus;covid-19;nigeria;palliatives

Journal Article

Eranga, Isaac Omo-Ehiabhi

10.21106/ijma.394

[Title]: COVID-19 Pandemic in Nigeria: Palliative Measures and the Politics of Vulnerability. [Abstract]: In a bid to slow the rate of spread of the virus, the Federal Government of Nigeria, on several occasions, imposed targeted lockdown measures in areas with rapid increase of Covid-19 cases. The states in which the federal government imposed the targeted lockdown included Lagos, Ogun, and the Federal Capital Territory in Abuja. Some States in the country imposed partial lockdown and closure of interstate boarders. Curfews have also been introduced in all the states nationwide. To alleviate the effects of the lockdown, the Federal Government of Nigeria rolled out palliative measures for targeted groups. However, lamentations have trailed the distribution of government palliatives by the masses. Citizens allege that the process of distribution of palliatives had been politicized. [Keywords]: corona virus;covid-19;nigeria;palliatives

Cell

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.

covid-19;il-17a;kawasaki disease;mis-c;sars-cov-2;autoantibodies;hyperinflammation in children;multisystem inflammatory syndrome in children;systems immunology

Journal Article;Research Support, Non-U.S. Gov't

Consiglio, Camila Rosat;Cotugno, Nicola;Sardh, Fabian;Pou, Christian;Amodio, Donato;Rodriguez, Lucie;Tan, Ziyang;Zicari, Sonia;Ruggiero, Alessandra;Pascucci, Giuseppe Rubens;Santilli, Veronica;Campbell, Tessa;Bryceson, Yenan;Eriksson, Daniel;Wang, Jun;Marchesi, Alessandra;Lakshmikanth, Tadepally;Campana, Andrea;Villani, Alberto;Rossi, Paolo;Landegren, Nils;Palma, Paolo;Brodin, Petter

10.1016/j.cell.2020.09.016

[Title]: The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. [Abstract]: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C. [Keywords]: covid-19;il-17a;kawasaki disease;mis-c;sars-cov-2;autoantibodies;hyperinflammation in children;multisystem inflammatory syndrome in children;systems immunology

BMC Med

Epidemiological and clinical features of pediatric COVID-19.

BACKGROUND: COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children. METHODS: A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities. RESULTS: Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21). CONCLUSIONS: Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( chictr.org.cn ) identifier: ChiCTR2000030464.

covid-19;clinical features;coronavirus;epidemiology;pediatric;sars-cov-2

Journal Article;Research Support, Non-U.S. Gov't

Guo, Cheng-Xian;He, Li;Yin, Ji-Ye;Meng, Xiang-Guang;Tan, Wei;Yang, Guo-Ping;Bo, Tao;Liu, Jun-Ping;Lin, Xin-Jian;Chen, Xiang

10.1186/s12916-020-01719-2

[Title]: Epidemiological and clinical features of pediatric COVID-19. [Abstract]: BACKGROUND: COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children. METHODS: A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities. RESULTS: Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21). CONCLUSIONS: Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( chictr.org.cn ) identifier: ChiCTR2000030464. [Keywords]: covid-19;clinical features;coronavirus;epidemiology;pediatric;sars-cov-2

Engineering (Beijing)

Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications.

The COVID-19 pandemic has led to worldwide efforts to understand the biological traits of the newly identified HCoV-19 virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 S protein, 20 are completely occupied by N-glycans, predominantly of the oligomannose type. All seven glycosylation sites in human angiotensin I converting enzyme 2 (hACE2) were found to be completely occupied, mainly by complex N-glycans. However, glycosylation did not directly contribute to the binding affinity between HCoV-19 S and hACE2. Additional post-translational modification (PTM) was identified, including multiple methylated sites in both proteins and multiple sites with hydroxylproline in hACE2. Refined structural models of HCoV-19 S and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy (cryo-EM) structures. The PTM and glycan maps of HCoV-19 S and hACE2 provide additional structural details for studying the mechanisms underlying host attachment and the immune response of HCoV-19, as well as knowledge for developing desperately needed remedies and vaccines.

covid-19;n-glycosylation;spike protein;structure;hace2

Journal Article

Sun, Zeyu;Ren, Keyi;Zhang, Xing;Chen, Jinghua;Jiang, Zhengyi;Jiang, Jing;Ji, Feiyang;Ouyang, Xiaoxi;Li, Lanjuan

10.1016/j.eng.2020.07.014

[Title]: Mass Spectrometry Analysis of Newly Emerging Coronavirus HCoV-19 Spike Protein and Human ACE2 Reveals Camouflaging Glycans and Unique Post-Translational Modifications. [Abstract]: The COVID-19 pandemic has led to worldwide efforts to understand the biological traits of the newly identified HCoV-19 virus. In this mass spectrometry (MS)-based study, we reveal that out of 21 possible glycosites in the HCoV-19 S protein, 20 are completely occupied by N-glycans, predominantly of the oligomannose type. All seven glycosylation sites in human angiotensin I converting enzyme 2 (hACE2) were found to be completely occupied, mainly by complex N-glycans. However, glycosylation did not directly contribute to the binding affinity between HCoV-19 S and hACE2. Additional post-translational modification (PTM) was identified, including multiple methylated sites in both proteins and multiple sites with hydroxylproline in hACE2. Refined structural models of HCoV-19 S and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy (cryo-EM) structures. The PTM and glycan maps of HCoV-19 S and hACE2 provide additional structural details for studying the mechanisms underlying host attachment and the immune response of HCoV-19, as well as knowledge for developing desperately needed remedies and vaccines. [Keywords]: covid-19;n-glycosylation;spike protein;structure;hace2

Front Immunol

Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS.

Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed "original antigenic sin." The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.

covid-19;sars-cov-2;antibody dependent enhancement (ade);antigenic sin;cross-reactivity;protecting igg;receptor binding protein;spike protein

Journal Article

Fierz, Walter;Walz, Brigitte

10.3389/fimmu.2020.01120

[Title]: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS. [Abstract]: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed "original antigenic sin." The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera. [Keywords]: covid-19;sars-cov-2;antibody dependent enhancement (ade);antigenic sin;cross-reactivity;protecting igg;receptor binding protein;spike protein

Clin Infect Dis

Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China.

BACKGROUND: In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. METHODS: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection. RESULTS: Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases. CONCLUSIONS: The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.

covid-19;t lymphocyte;immune response;lymphocyte subsets

Journal Article

Qin, Chuan;Zhou, Luoqi;Hu, Ziwei;Zhang, Shuoqi;Yang, Sheng;Tao, Yu;Xie, Cuihong;Ma, Ke;Shang, Ke;Wang, Wei;Tian, Dai-Shi

10.1093/cid/ciaa248

[Title]: Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. [Abstract]: BACKGROUND: In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. METHODS: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection. RESULTS: Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases. CONCLUSIONS: The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19. [Keywords]: covid-19;t lymphocyte;immune response;lymphocyte subsets

Angiology

Interaction Between Coronavirus S-Protein and Human ACE2: Hints for Exploring Efficient Therapeutic Targets to Treat COVID-19.

With the global expansion of coronavirus disease 2019 (COVID-19) and the declaration of its outbreak as a Public Health Emergency of International Concern by the World Health Organization, there is an urgent need for vaccines and medicines to prevent and treat COVID-19. The responsible pathogen for the disease is the newly severe acute respiratory syndrome coronavirus (SARS-CoV) 2 belonging to the same family of viruses SARS-CoV and Middle East respiratory syndrome coronavirus that originally are zoonotic and have been associated with severe illness during the outbreaks in 2003 and 2012, respectively. The virulence of coronavirus strains is mainly associated with variations in surface proteins mediating cellular entry of the virus, which can help in finding effective therapeutic targets. In this review, we seek evidence showing the role of coronavirus spike protein (S-protein) and its potential cellular receptor, angiotensin-converting enzyme 2 (ACE2), during infection of coronaviruses, including the newly SARS-CoV-2 and its similar strain SARS-CoV. This review also discusses the therapeutic effect of inhibiting the renin-angiotensin system cascade, a target of ACE2, in patients having coronavirus with cardiovascular disease.

covid-19;angiotensin-converting enzyme 2;coronavirus;renin-angiotensin system;spike protein

Journal Article;Review

Momtazi-Borojeni, Amir Abbas;Banach, Maciej;Reiner, Zeljko;Pirro, Matteo;Bianconi, Vanessa;Al-Rasadi, Khalid;Sahebkar, Amirhossein

10.1177/0003319720952284

[Title]: Interaction Between Coronavirus S-Protein and Human ACE2: Hints for Exploring Efficient Therapeutic Targets to Treat COVID-19. [Abstract]: With the global expansion of coronavirus disease 2019 (COVID-19) and the declaration of its outbreak as a Public Health Emergency of International Concern by the World Health Organization, there is an urgent need for vaccines and medicines to prevent and treat COVID-19. The responsible pathogen for the disease is the newly severe acute respiratory syndrome coronavirus (SARS-CoV) 2 belonging to the same family of viruses SARS-CoV and Middle East respiratory syndrome coronavirus that originally are zoonotic and have been associated with severe illness during the outbreaks in 2003 and 2012, respectively. The virulence of coronavirus strains is mainly associated with variations in surface proteins mediating cellular entry of the virus, which can help in finding effective therapeutic targets. In this review, we seek evidence showing the role of coronavirus spike protein (S-protein) and its potential cellular receptor, angiotensin-converting enzyme 2 (ACE2), during infection of coronaviruses, including the newly SARS-CoV-2 and its similar strain SARS-CoV. This review also discusses the therapeutic effect of inhibiting the renin-angiotensin system cascade, a target of ACE2, in patients having coronavirus with cardiovascular disease. [Keywords]: covid-19;angiotensin-converting enzyme 2;coronavirus;renin-angiotensin system;spike protein

ACS Infect Dis

Current and Perspective Diagnostic Techniques for COVID-19.

Since late December 2019, the coronavirus pandemic (COVID-19; previously known as 2019-nCoV) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been surging rapidly around the world. With more than 1,700,000 confirmed cases, the world faces an unprecedented economic, social, and health impact. The early, rapid, sensitive, and accurate diagnosis of viral infection provides rapid responses for public health surveillance, prevention, and control of contagious diffusion. More than 30% of the confirmed cases are asymptomatic, and the high false-negative rate (FNR) of a single assay requires the development of novel diagnostic techniques, combinative approaches, sampling from different locations, and consecutive detection. The recurrence of discharged patients indicates the need for long-term monitoring and tracking. Diagnostic and therapeutic methods are evolving with a deeper understanding of virus pathology and the potential for relapse. In this Review, a comprehensive summary and comparison of different SARS-CoV-2 diagnostic methods are provided for researchers and clinicians to develop appropriate strategies for the timely and effective detection of SARS-CoV-2. The survey of current biosensors and diagnostic devices for viral nucleic acids, proteins, and particles and chest tomography will provide insight into the development of novel perspective techniques for the diagnosis of COVID-19.

covid-19;sars-cov-2;biosensors;diagnostics;immunoassay;molecular diagnostics

Journal Article;Research Support, Non-U.S. Gov't;Review

Yuan, Xi;Yang, Chengming;He, Qian;Chen, Junhu;Yu, Dongmei;Li, Jie;Zhai, Shiyao;Qin, Zhifeng;Du, Ke;Chu, Zhenhai;Qin, Peiwu

10.1021/acsinfecdis.0c00365

[Title]: Current and Perspective Diagnostic Techniques for COVID-19. [Abstract]: Since late December 2019, the coronavirus pandemic (COVID-19; previously known as 2019-nCoV) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been surging rapidly around the world. With more than 1,700,000 confirmed cases, the world faces an unprecedented economic, social, and health impact. The early, rapid, sensitive, and accurate diagnosis of viral infection provides rapid responses for public health surveillance, prevention, and control of contagious diffusion. More than 30% of the confirmed cases are asymptomatic, and the high false-negative rate (FNR) of a single assay requires the development of novel diagnostic techniques, combinative approaches, sampling from different locations, and consecutive detection. The recurrence of discharged patients indicates the need for long-term monitoring and tracking. Diagnostic and therapeutic methods are evolving with a deeper understanding of virus pathology and the potential for relapse. In this Review, a comprehensive summary and comparison of different SARS-CoV-2 diagnostic methods are provided for researchers and clinicians to develop appropriate strategies for the timely and effective detection of SARS-CoV-2. The survey of current biosensors and diagnostic devices for viral nucleic acids, proteins, and particles and chest tomography will provide insight into the development of novel perspective techniques for the diagnosis of COVID-19. [Keywords]: covid-19;sars-cov-2;biosensors;diagnostics;immunoassay;molecular diagnostics

Aging (Albany NY)

Questionnaire assessment helps the self-management of patients with inflammatory bowel disease during the outbreak of Coronavirus Disease 2019.

OBJECTIVE: This study aimed to assess the disease conditions of patients with inflammatory bowel disease (IBD) in Hubei Province during the outbreak of Coronavirus Disease 2019 (COVID-19) by questionnaire online and guide their self-management during this epidemic. RESULTS: A total of 102 eligible questionnaires were included. No patient we surveyed reported a diagnosis of COVID-19. Our result showed that 67.86% of patients with ulcerative colitis (UC) and 80.43% of patients with Crohn's disease (CD) were in remission, 85.29%of patients had a good quality of life. Part of the patients (21.57%) reported their disease conditions worsening. The reduction in physical exercise was a risk factor for worsening conditions (OR=17.593, p=0.009). Some patients reported an alteration of medication regimens during the epidemic. CONCLUSIONS: The epidemic of COVID-19 might have a certain impact on many aspects of Hubei IBD patients within four weeks after the traffic control. Doctors could utilize the results from our questionnaire to guide IBD patients' self-management. METHODS: A questionnaire was designed containing the Harvey-Bradshaw Index (HBI), the 6-point Mayo Score, the short inflammatory bowel disease questionnaire (SIBDQ) and distributed to Hubei IBD patients online within four weeks of traffic control after the outbreak, it also included questions about patients' self-reported disease conditions and their epidemiological features of COVID-19.

covid-19;inflammatory bowel disease;questionnaire;self-management

Journal Article;Research Support, Non-U.S. Gov't

Yu, Meiping;Ye, Zhenghao;Chen, Yu;Qin, Tingting;Kou, Jiguang;Tian, De'an;Xiao, Fang

10.18632/aging.103525

[Title]: Questionnaire assessment helps the self-management of patients with inflammatory bowel disease during the outbreak of Coronavirus Disease 2019. [Abstract]: OBJECTIVE: This study aimed to assess the disease conditions of patients with inflammatory bowel disease (IBD) in Hubei Province during the outbreak of Coronavirus Disease 2019 (COVID-19) by questionnaire online and guide their self-management during this epidemic. RESULTS: A total of 102 eligible questionnaires were included. No patient we surveyed reported a diagnosis of COVID-19. Our result showed that 67.86% of patients with ulcerative colitis (UC) and 80.43% of patients with Crohn's disease (CD) were in remission, 85.29%of patients had a good quality of life. Part of the patients (21.57%) reported their disease conditions worsening. The reduction in physical exercise was a risk factor for worsening conditions (OR=17.593, p=0.009). Some patients reported an alteration of medication regimens during the epidemic. CONCLUSIONS: The epidemic of COVID-19 might have a certain impact on many aspects of Hubei IBD patients within four weeks after the traffic control. Doctors could utilize the results from our questionnaire to guide IBD patients' self-management. METHODS: A questionnaire was designed containing the Harvey-Bradshaw Index (HBI), the 6-point Mayo Score, the short inflammatory bowel disease questionnaire (SIBDQ) and distributed to Hubei IBD patients online within four weeks of traffic control after the outbreak, it also included questions about patients' self-reported disease conditions and their epidemiological features of COVID-19. [Keywords]: covid-19;inflammatory bowel disease;questionnaire;self-management

J Public Health (Oxf)

Picture of a pandemic: visual aids in the COVID-19 crisis.

As a global crisis, COVID-19 has underscored the challenge of disseminating evidence-based public health recommendations amidst a rapidly evolving, often uncensored information ecosystem-one fueled in part by an unprecedented degree of connected afforded through social media. In this piece, we explore an underdiscussed intersection between the visual arts and public health, focusing on the use of validated infographics and other forms of visual communication to rapidly disseminate accurate public health information during the COVID-19 pandemic. We illustrate our arguments through our own experience in creating a validated infographic for patients, now disseminated through social media and other outlets across the world in nearly 20 translations. Visual communication offers a creative and practical medium to bridge critical health literacy gaps, empower diverse patient communities through evidence-based information and facilitate public health advocacy during this pandemic and the 'new normal' that lies ahead.

covid-19;health literacy;patient education;social media;visual aid

Journal Article

Hamaguchi, Ryoko;Nematollahi, Saman;Minter, Daniel J

10.1093/pubmed/fdaa080

[Title]: Picture of a pandemic: visual aids in the COVID-19 crisis. [Abstract]: As a global crisis, COVID-19 has underscored the challenge of disseminating evidence-based public health recommendations amidst a rapidly evolving, often uncensored information ecosystem-one fueled in part by an unprecedented degree of connected afforded through social media. In this piece, we explore an underdiscussed intersection between the visual arts and public health, focusing on the use of validated infographics and other forms of visual communication to rapidly disseminate accurate public health information during the COVID-19 pandemic. We illustrate our arguments through our own experience in creating a validated infographic for patients, now disseminated through social media and other outlets across the world in nearly 20 translations. Visual communication offers a creative and practical medium to bridge critical health literacy gaps, empower diverse patient communities through evidence-based information and facilitate public health advocacy during this pandemic and the 'new normal' that lies ahead. [Keywords]: covid-19;health literacy;patient education;social media;visual aid

Ophthalmol Ther

Does the COVID-19 Pandemic Spell the End for the Direct Ophthalmoscope?

Despite advances in ophthalmic diagnostics, the direct ophthalmoscope remains a key clinical skill taught to medical students and is the tool of choice for retina examination among non-ophthalmic physicians. However, in recent years viable alternatives have become available. The coronavirus disease 2019 (COVID-19) pandemic has forced a major re-thinking in medical education worldwide. In this commentary, we examined the current merits and limitations of the direct ophthalmoscope in both the clinical sense and in the context of infection control. Furthermore, we compared the direct ophthalmoscope with alternatives, including commercially available portable non-mydriatic fundus cameras, that would allow a change in focus during ophthalmic teaching. We concluded that the latter will better prepare our medical students for the age of telemedicine and deep-learning systems. While the COVID-19 pandemic will not be the sole reason for the 'death' of the direct ophthalmoscope, the global situation will inevitably serve to expedite long overdue changes in our teaching of ophthalmic skills to non-ophthalmic physicians.

covid-19;direct ophthalmoscopy;medical education;pandemic

Letter

Shih, Kendrick C;Chau, Charlene Y C;Chan, Jonathan C H;Wong, Jasper K W;Lai, Jimmy S M

10.1007/s40123-020-00295-1

[Title]: Does the COVID-19 Pandemic Spell the End for the Direct Ophthalmoscope? [Abstract]: Despite advances in ophthalmic diagnostics, the direct ophthalmoscope remains a key clinical skill taught to medical students and is the tool of choice for retina examination among non-ophthalmic physicians. However, in recent years viable alternatives have become available. The coronavirus disease 2019 (COVID-19) pandemic has forced a major re-thinking in medical education worldwide. In this commentary, we examined the current merits and limitations of the direct ophthalmoscope in both the clinical sense and in the context of infection control. Furthermore, we compared the direct ophthalmoscope with alternatives, including commercially available portable non-mydriatic fundus cameras, that would allow a change in focus during ophthalmic teaching. We concluded that the latter will better prepare our medical students for the age of telemedicine and deep-learning systems. While the COVID-19 pandemic will not be the sole reason for the 'death' of the direct ophthalmoscope, the global situation will inevitably serve to expedite long overdue changes in our teaching of ophthalmic skills to non-ophthalmic physicians. [Keywords]: covid-19;direct ophthalmoscopy;medical education;pandemic

Int J Cancer

The European response to the WHO call to eliminate cervical cancer as a public health problem.

The age-standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women-years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost-effective; they should introduce organised population-based HPV-based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self-samples for nonscreened or underscreened women; and to manage 90% of screen-positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence-based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID-19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high-risk women and adhere to cost-effective policies including self-sampling.

covid-19;europe;hpv vaccination;who;cervical cancer screening;elimination of cervical cancer

Journal Article;Research Support, Non-U.S. Gov't

Arbyn, Marc;Gultekin, Murat;Morice, Philippe;Nieminen, Pekka;Cruickshank, Maggie;Poortmans, Philip;Kelly, Daniel;Poljak, Mario;Bergeron, Christine;Ritchie, David;Schmidt, Dietmar;Kyrgiou, Maria;Van den Bruel, Ann;Bruni, Laia;Basu, Partha;Bray, Freddie;Weiderpass, Elisabete

10.1002/ijc.33189

[Title]: The European response to the WHO call to eliminate cervical cancer as a public health problem. [Abstract]: The age-standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women-years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost-effective; they should introduce organised population-based HPV-based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self-samples for nonscreened or underscreened women; and to manage 90% of screen-positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence-based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID-19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high-risk women and adhere to cost-effective policies including self-sampling. [Keywords]: covid-19;europe;hpv vaccination;who;cervical cancer screening;elimination of cervical cancer

J Am Soc Nephrol

AKI in Hospitalized Patients with and without COVID-19: A Comparison Study.

BACKGROUND: Reports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection. METHODS: In a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19. RESULTS: We found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (>50 years). Male sex and age >50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level. CONCLUSIONS: Patients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19.

aki;covid-19;outcomes;race;risk factors;sex

Comparative Study;Journal Article

Fisher, Molly;Neugarten, Joel;Bellin, Eran;Yunes, Milagros;Stahl, Lindsay;Johns, Tanya S;Abramowitz, Matthew K;Levy, Rebecca;Kumar, Neelja;Mokrzycki, Michele H;Coco, Maria;Dominguez, Mary;Prudhvi, Kalyan;Golestaneh, Ladan

10.1681/ASN.2020040509

[Title]: AKI in Hospitalized Patients with and without COVID-19: A Comparison Study. [Abstract]: BACKGROUND: Reports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection. METHODS: In a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19. RESULTS: We found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (>50 years). Male sex and age >50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level. CONCLUSIONS: Patients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19. [Keywords]: aki;covid-19;outcomes;race;risk factors;sex

J Infect Dev Ctries

Short epidemiological overview of the current situation on COVID-19 pandemic in Southeast European (SEE) countries.

We are living in times where a viral disease has brought normal life in much of the world to a halt. The novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) started in December 2019 in Wuhan, China initially and in a short time crossed the European borders. After mitigating the epidemic in China, Italy became one of the most COVID-19 affected countries worldwide. International travelers are important sources of infectious diseases and a possible source of epidemic. Due to its political, geographic, and cultural similarities, Italy is one of the main economic partners of Southeast European (SEE) countries. Our data show that infection in index cases in all 11 SEE countries was travel-related with Italy being a source country for 8/11 countries. After the first case identifications on February 25, the number of cases in SEE countries is continually rising reaching the total number of 15,612 with 565 fatal cases and overall case fatality ratio (CFR) of 3.6 (median 3.8, range 0.8-5.5) by April 10, 2020. At a time when the COVID-19 pandemic is approaching its peak, apart from the problems with treatment of the disease and care for critically ill patients, there are other equally important problems, such as organization of outbreak response, provision of health care, lack of hospital personnel, disruption of personal protective equipment supply chains and health care workers (HCWs) protection. But what is more important is the heroic behavior of the HCWs who are showing their humanity by disregarding their lives.

covid-19;sars-cov-2;southeast european (see) countries;healthcare workers;pandemic

Journal Article;Review

Puca, Edmond;Civljak, Rok;Arapovic, Jurica;Popescu, Corneliu;Christova, Iva;Raka, Lul;Cana, Fadil;Miranovic, Vesna;Karageorgopoulos, Drosos;Bas, Denis;Paglietti, Bianca;Barac, Aleksandra

10.3855/jidc.12814

[Title]: Short epidemiological overview of the current situation on COVID-19 pandemic in Southeast European (SEE) countries. [Abstract]: We are living in times where a viral disease has brought normal life in much of the world to a halt. The novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) started in December 2019 in Wuhan, China initially and in a short time crossed the European borders. After mitigating the epidemic in China, Italy became one of the most COVID-19 affected countries worldwide. International travelers are important sources of infectious diseases and a possible source of epidemic. Due to its political, geographic, and cultural similarities, Italy is one of the main economic partners of Southeast European (SEE) countries. Our data show that infection in index cases in all 11 SEE countries was travel-related with Italy being a source country for 8/11 countries. After the first case identifications on February 25, the number of cases in SEE countries is continually rising reaching the total number of 15,612 with 565 fatal cases and overall case fatality ratio (CFR) of 3.6 (median 3.8, range 0.8-5.5) by April 10, 2020. At a time when the COVID-19 pandemic is approaching its peak, apart from the problems with treatment of the disease and care for critically ill patients, there are other equally important problems, such as organization of outbreak response, provision of health care, lack of hospital personnel, disruption of personal protective equipment supply chains and health care workers (HCWs) protection. But what is more important is the heroic behavior of the HCWs who are showing their humanity by disregarding their lives. [Keywords]: covid-19;sars-cov-2;southeast european (see) countries;healthcare workers;pandemic

Biology (Basel)

Loop-Mediated Isothermal Amplification (LAMP): A Rapid, Sensitive, Specific, and Cost-Effective Point-of-Care Test for Coronaviruses in the Context of COVID-19 Pandemic.

The rampant spread of COVID-19 and the worldwide prevalence of infected cases demand a rapid, simple, and cost-effective Point of Care Test (PoCT) for the accurate diagnosis of this pandemic. The most common molecular tests approved by regulatory bodies across the world for COVID-19 diagnosis are based on Polymerase Chain Reaction (PCR). While PCR-based tests are highly sensitive, specific, and remarkably reliable, they have many limitations ranging from the requirement of sophisticated laboratories, need of skilled personnel, use of complex protocol, long wait times for results, and an overall high cost per test. These limitations have inspired researchers to search for alternative diagnostic methods that are fast, economical, and executable in low-resource laboratory settings. The discovery of Loop-mediated isothermal Amplification (LAMP) has provided a reliable substitute platform for the accurate detection of low copy number nucleic acids in the diagnosis of several viral diseases, including epidemics like Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). At present, a cocktail of LAMP assay reagents along with reverse transcriptase enzyme (Reverse Transcription LAMP, RT-LAMP) can be a robust solution for the rapid and cost-effective diagnosis for COVID-19, particularly in developing, and low-income countries. In summary, the development of RT-LAMP based diagnostic tools in a paper/strip format or the integration of this method into a microfluidic platform such as a Lab-on-a-chip may revolutionize the concept of PoCT for COVID-19 diagnosis. This review discusses the principle, technology and past research underpinning the success for using this method for diagnosing MERS and SARS, in addition to ongoing research, and the prominent prospect of RT-LAMP in the context of COVID-19 diagnosis.

covid-19;lamp;rt-lamp;sars-cov-2;coronavirus;point-of-care tests;reverse transcription loop-mediated isothermal amplification

Journal Article;Review

Augustine, Robin;Hasan, Anwarul;Das, Suvarthi;Ahmed, Rashid;Mori, Yasuyoshi;Notomi, Tsugunori;Kevadiya, Bhavesh D;Thakor, Avnesh S

10.3390/biology9080182

[Title]: Loop-Mediated Isothermal Amplification (LAMP): A Rapid, Sensitive, Specific, and Cost-Effective Point-of-Care Test for Coronaviruses in the Context of COVID-19 Pandemic. [Abstract]: The rampant spread of COVID-19 and the worldwide prevalence of infected cases demand a rapid, simple, and cost-effective Point of Care Test (PoCT) for the accurate diagnosis of this pandemic. The most common molecular tests approved by regulatory bodies across the world for COVID-19 diagnosis are based on Polymerase Chain Reaction (PCR). While PCR-based tests are highly sensitive, specific, and remarkably reliable, they have many limitations ranging from the requirement of sophisticated laboratories, need of skilled personnel, use of complex protocol, long wait times for results, and an overall high cost per test. These limitations have inspired researchers to search for alternative diagnostic methods that are fast, economical, and executable in low-resource laboratory settings. The discovery of Loop-mediated isothermal Amplification (LAMP) has provided a reliable substitute platform for the accurate detection of low copy number nucleic acids in the diagnosis of several viral diseases, including epidemics like Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). At present, a cocktail of LAMP assay reagents along with reverse transcriptase enzyme (Reverse Transcription LAMP, RT-LAMP) can be a robust solution for the rapid and cost-effective diagnosis for COVID-19, particularly in developing, and low-income countries. In summary, the development of RT-LAMP based diagnostic tools in a paper/strip format or the integration of this method into a microfluidic platform such as a Lab-on-a-chip may revolutionize the concept of PoCT for COVID-19 diagnosis. This review discusses the principle, technology and past research underpinning the success for using this method for diagnosing MERS and SARS, in addition to ongoing research, and the prominent prospect of RT-LAMP in the context of COVID-19 diagnosis. [Keywords]: covid-19;lamp;rt-lamp;sars-cov-2;coronavirus;point-of-care tests;reverse transcription loop-mediated isothermal amplification

PLoS Med

Pandemic responses: Planning to neutralize SARS-CoV-2 and prepare for future outbreaks.

The PLOS Medicine Editors discuss the current SARS-CoV-2 outbreak and implications for global health.

Editorial;Comment

10.1371/journal.pmed.1003123

[Title]: Pandemic responses: Planning to neutralize SARS-CoV-2 and prepare for future outbreaks. [Abstract]: The PLOS Medicine Editors discuss the current SARS-CoV-2 outbreak and implications for global health. [Keywords]:

Exp Eye Res

Occurrence of SARS-CoV-2 in the intraocular milieu.

The purpose of this research is to study the intraocular occurrence of SARS-CoV-2. In postmortem examinations, aqueous humor and the vitreous samples were collected. All individuals were previously positive in nasopharyngeal swabbing and cause of death was respiratory failure due to SARS-CoV-2 infection. Testing was done using quantitative RT-PCR. We included 16 aqueous humor and 16 vitreous samples for PCR testing. None of the results was positive for SARS-CoV-2. Human GAPDH genes to verify the presence of RNA was present in all aqueous humor samples (16/16, 100%) and 15/16 (93.8%) vitreous samples. In conclusion, this case series found no evidence of SARS-CoV-2 in the intraocular milieu.

aqueous humor;intraocular milieu;sars-cov-2;vitreous body

Journal Article;Review

List, Wolfgang;Regitnig, Peter;Kashofer, Karl;Gorkiewicz, Gregor;Zacharias, Martin;Wedrich, Andreas;Posch-Pertl, Laura

10.1016/j.exer.2020.108273

[Title]: Occurrence of SARS-CoV-2 in the intraocular milieu. [Abstract]: The purpose of this research is to study the intraocular occurrence of SARS-CoV-2. In postmortem examinations, aqueous humor and the vitreous samples were collected. All individuals were previously positive in nasopharyngeal swabbing and cause of death was respiratory failure due to SARS-CoV-2 infection. Testing was done using quantitative RT-PCR. We included 16 aqueous humor and 16 vitreous samples for PCR testing. None of the results was positive for SARS-CoV-2. Human GAPDH genes to verify the presence of RNA was present in all aqueous humor samples (16/16, 100%) and 15/16 (93.8%) vitreous samples. In conclusion, this case series found no evidence of SARS-CoV-2 in the intraocular milieu. [Keywords]: aqueous humor;intraocular milieu;sars-cov-2;vitreous body

J Gynecol Obstet Hum Reprod

Post-natal follow-up for women and neonates during the COVID-19 pandemic: French National Authority for Health recommendations.

Introduction: In the context of the stage 3 SARS-Cov-2 epidemic situation, it is necessary to put forward a method of rapid response for an HAS position statement in order to answer to the requests from the French Ministry of Solidarity and Health, healthcare professionals and/or health system users' associations, concerning post-natal follow-up for women and neonates during the COVID-19 pandemic. Methods: A simplified 7-step process that favours HAS collaboration with experts (healthcare professionals, health system users' associations, scientific societies etc.), the restrictive selection of available evidence and the use of digital means of communication. A short and specific dissemination format, which can be quickly updated in view of the changes in available data has been chosen.

Journal Article;Practice Guideline

Vivanti, Alexandre J;Deruelle, Philippe;Picone, Olivier;Guillaume, Sophie;Roze, Jean-Christophe;Mulin, Blandine;Kochert, Fabienne;De Beco, Isabelle;Mahut, Sophie;Gantois, Adrien;Barasinski, Chloe;Petitprez, Karine;Pauchet-Traversat, Anne-Francoise;Droy, Alcyone;Benachi, Alexandra

10.1016/j.jogoh.2020.101805

[Title]: Post-natal follow-up for women and neonates during the COVID-19 pandemic: French National Authority for Health recommendations. [Abstract]: Introduction: In the context of the stage 3 SARS-Cov-2 epidemic situation, it is necessary to put forward a method of rapid response for an HAS position statement in order to answer to the requests from the French Ministry of Solidarity and Health, healthcare professionals and/or health system users' associations, concerning post-natal follow-up for women and neonates during the COVID-19 pandemic. Methods: A simplified 7-step process that favours HAS collaboration with experts (healthcare professionals, health system users' associations, scientific societies etc.), the restrictive selection of available evidence and the use of digital means of communication. A short and specific dissemination format, which can be quickly updated in view of the changes in available data has been chosen. [Keywords]:

New Microbes New Infect

Preliminary report of in vitro and in vivo effectiveness of dornase alfa on SARS-CoV-2 infection.

Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). It is well known that novel coronavirus disease 2019 (COVID-19) pneumonia progresses to ARDS and even multiple organ failure. High blood neutrophil levels are an early indicator of COVID-19 and predict severe respiratory diseases. Also it is reported that mucus structure in COVID-19 is very similar to that in cystic fibrosis due to the accumulation of excessive NET in the lungs. In this study, we showed the recovery of three individuals with COVID-19 after including dornase alfa in their treatment. We followed clinical improvement in the radiological analysis (two of three cases), oxygen saturation (Spo2), respiratory rate, disappearance of dyspnoea, coughing and a decrease in NET formation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load after the treatment. Also here, we share our preliminary results suggesting that dornase alfa has an anti-viral effect against SARS-CoV-2 infection in a green monkey kidney cell line, Vero, and a bovine kidney cell line, MDBK, without determined cytotoxicity on healthy peripheral blood mononuclear cells.

coronavirus disease 2019;netosis;dornase alfa;neutrophil extracellular traps;severe acute respiratory syndrome coronavirus 2

Case Reports

Okur, H K;Yalcin, K;Tastan, C;Demir, S;Yurtsever, B;Karakus, G S;Kancagi, D D;Abanuz, S;Seyis, U;Zengin, R;Hemsinlioglu, C;Kara, M;Yildiz, M E;Deliceo, E;Birgen, N;Pelit, N B;Cuhadaroglu, C;Kocagoz, A S;Ovali, E

10.1016/j.nmni.2020.100756

[Title]: Preliminary report of in vitro and in vivo effectiveness of dornase alfa on SARS-CoV-2 infection. [Abstract]: Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). It is well known that novel coronavirus disease 2019 (COVID-19) pneumonia progresses to ARDS and even multiple organ failure. High blood neutrophil levels are an early indicator of COVID-19 and predict severe respiratory diseases. Also it is reported that mucus structure in COVID-19 is very similar to that in cystic fibrosis due to the accumulation of excessive NET in the lungs. In this study, we showed the recovery of three individuals with COVID-19 after including dornase alfa in their treatment. We followed clinical improvement in the radiological analysis (two of three cases), oxygen saturation (Spo2), respiratory rate, disappearance of dyspnoea, coughing and a decrease in NET formation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load after the treatment. Also here, we share our preliminary results suggesting that dornase alfa has an anti-viral effect against SARS-CoV-2 infection in a green monkey kidney cell line, Vero, and a bovine kidney cell line, MDBK, without determined cytotoxicity on healthy peripheral blood mononuclear cells. [Keywords]: coronavirus disease 2019;netosis;dornase alfa;neutrophil extracellular traps;severe acute respiratory syndrome coronavirus 2

J Mol Biol

Phylogenetic Analysis and Structural Modeling of SARS-CoV-2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop.

The 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) originally arose as part of a major outbreak of respiratory disease centered on Hubei province, China. It is now a global pandemic and is a major public health concern. Taxonomically, SARS-CoV-2 was shown to be a Betacoronavirus (lineage B) closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been reported to share a common receptor with SARS-CoV (ACE-2). Subsequently, betacoronaviruses from pangolins were identified as close relatives to SARS-CoV-2. Here, we perform structural modeling of the SARS-CoV-2 spike glycoprotein. Our data provide support for the similar receptor utilization between SARS-CoV-2 and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV and all other coronaviruses in Betacoronavirus lineage B, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains. We suggest this loop confers fusion activation and entry properties more in line with betacoronaviruses in lineages A and C, and be a key component in the evolution of SARS-CoV-2 with this structural loop affecting virus stability and transmission.

covid-19;sars-cov-2;cleavage sites;coronavirus;spike protein

Journal Article;Research Support, N.I.H., Extramural

Jaimes, Javier A;Andre, Nicole M;Chappie, Joshua S;Millet, Jean K;Whittaker, Gary R

10.1016/j.jmb.2020.04.009

[Title]: Phylogenetic Analysis and Structural Modeling of SARS-CoV-2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop. [Abstract]: The 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) originally arose as part of a major outbreak of respiratory disease centered on Hubei province, China. It is now a global pandemic and is a major public health concern. Taxonomically, SARS-CoV-2 was shown to be a Betacoronavirus (lineage B) closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been reported to share a common receptor with SARS-CoV (ACE-2). Subsequently, betacoronaviruses from pangolins were identified as close relatives to SARS-CoV-2. Here, we perform structural modeling of the SARS-CoV-2 spike glycoprotein. Our data provide support for the similar receptor utilization between SARS-CoV-2 and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV and all other coronaviruses in Betacoronavirus lineage B, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains. We suggest this loop confers fusion activation and entry properties more in line with betacoronaviruses in lineages A and C, and be a key component in the evolution of SARS-CoV-2 with this structural loop affecting virus stability and transmission. [Keywords]: covid-19;sars-cov-2;cleavage sites;coronavirus;spike protein

Sci Total Environ

Environmental side effects of the injudicious use of antimicrobials in the era of COVID-19.

Use of antimicrobials in the treatment and prevention of COVID-19, caused by novel coronavirus SARS-CoV-2, is on the rise. The increased use of antimicrobials can have serious consequences on the environment. Antibiotics have had a reasonable role in bacterial co-infections with regards to the management of COVID-19. However, recent evidences suggest that there has been injudicious prescription of antimicrobials. Moreover, a large number of people are self-medicating with antibiotics in a misguided attempt to protect themselves from the virus. This practice is especially prevalent in developing communities. Although common soaps are effective at inactivating enveloped viruses, such as the SARS-CoV-2, use of antibacterial products bearing biocides has increased during this pandemic. Current wastewater treatment techniques are unable to offer complete elimination of antibacterial biocides. These compounds can then accumulate in different environmental compartments thus, disrupting the functioning of native microbes. These microbes are involved in the biogeochemical cycling of elements and environmental remediation. In addition, the presence of antimicrobial elements in the environment can stimulate antimicrobial resistance. Concrete actions are needed to address this issue. Development of an antimicrobial policy specific for COVID-19 is urgently needed. Investments into improving wastewater infrastructure as well as public awareness is crucial. Moreover, global monitoring programs and multidisciplinary collaborations are required to understand the environmental impact of this pandemics.

antibacterial soaps;antibiotics in environment;antimicrobial resistance (amr);covid-19;wastewater contamination

Journal Article

Usman, Muhammad;Farooq, Muhammad;Hanna, Khalil

10.1016/j.scitotenv.2020.141053

[Title]: Environmental side effects of the injudicious use of antimicrobials in the era of COVID-19. [Abstract]: Use of antimicrobials in the treatment and prevention of COVID-19, caused by novel coronavirus SARS-CoV-2, is on the rise. The increased use of antimicrobials can have serious consequences on the environment. Antibiotics have had a reasonable role in bacterial co-infections with regards to the management of COVID-19. However, recent evidences suggest that there has been injudicious prescription of antimicrobials. Moreover, a large number of people are self-medicating with antibiotics in a misguided attempt to protect themselves from the virus. This practice is especially prevalent in developing communities. Although common soaps are effective at inactivating enveloped viruses, such as the SARS-CoV-2, use of antibacterial products bearing biocides has increased during this pandemic. Current wastewater treatment techniques are unable to offer complete elimination of antibacterial biocides. These compounds can then accumulate in different environmental compartments thus, disrupting the functioning of native microbes. These microbes are involved in the biogeochemical cycling of elements and environmental remediation. In addition, the presence of antimicrobial elements in the environment can stimulate antimicrobial resistance. Concrete actions are needed to address this issue. Development of an antimicrobial policy specific for COVID-19 is urgently needed. Investments into improving wastewater infrastructure as well as public awareness is crucial. Moreover, global monitoring programs and multidisciplinary collaborations are required to understand the environmental impact of this pandemics. [Keywords]: antibacterial soaps;antibiotics in environment;antimicrobial resistance (amr);covid-19;wastewater contamination

Front Public Health

The Successes and Failures of the Initial COVID-19 Pandemic Response in Romania.

In the context of the COVID-19 pandemic, countries around the world varied in the strength and timeliness of their responses. In Romania, specific challenges were faced with regards to managing the spread and limiting the impact of the disease, ranging from healthcare infrastructure to demographic and sociocultural aspects. As the country has a sizeable diaspora, major difficulties were faced when large numbers of individuals from highly affected areas returned to Romania. However, the fast implementation of control measures successfully averted a surge in the number of COVID-19 cases. This delayed the overburdening of an already challenged healthcare system during the initial phases of the epidemic. Furthermore, early control was facilitated by the exploitation of communication channels that penetrated all layers of society, from ordinary citizens to governmental authorities and high-ranking religious figures. The management of the COVID-19 crisis in Romania illustrates the importance of a fast initial response which takes into account the role played by sociocultural aspects in the context of an epidemic. As the challenges faced by Romania are not unique, these results could inform future public health strategies worldwide.

covid-19;romania;coronavirus;diaspora;epidemic;pandemic;public health;sociocultural

Journal Article;Review

Dascalu, Stefan

10.3389/fpubh.2020.00344

[Title]: The Successes and Failures of the Initial COVID-19 Pandemic Response in Romania. [Abstract]: In the context of the COVID-19 pandemic, countries around the world varied in the strength and timeliness of their responses. In Romania, specific challenges were faced with regards to managing the spread and limiting the impact of the disease, ranging from healthcare infrastructure to demographic and sociocultural aspects. As the country has a sizeable diaspora, major difficulties were faced when large numbers of individuals from highly affected areas returned to Romania. However, the fast implementation of control measures successfully averted a surge in the number of COVID-19 cases. This delayed the overburdening of an already challenged healthcare system during the initial phases of the epidemic. Furthermore, early control was facilitated by the exploitation of communication channels that penetrated all layers of society, from ordinary citizens to governmental authorities and high-ranking religious figures. The management of the COVID-19 crisis in Romania illustrates the importance of a fast initial response which takes into account the role played by sociocultural aspects in the context of an epidemic. As the challenges faced by Romania are not unique, these results could inform future public health strategies worldwide. [Keywords]: covid-19;romania;coronavirus;diaspora;epidemic;pandemic;public health;sociocultural

Eye (Lond)

Assessing visible aerosol generation during vitrectomy in the era of Covid-19.

OBJECTIVE: To assess visible aerosol generation during simulated vitrectomy surgery. METHODS: A model comprising a human cadaveric corneoscleral rim mounted on an artificial anterior chamber was used. Three-port 25 gauge vitrectomy simulated surgery was performed with any visible aerosol production recorded using high-speed 4K camera. The following were assessed: (1) vitrector at maximum cut rate in static and dynamic conditions inside the model, (2) vitrector at air-fluid interface in a physical model, (3) passive fluid-air exchange with a backflush hand piece, (4) valved cannulas under air, and (5) a defective valved cannula under air. RESULTS: No visible aerosol or droplets were identified when the vitrector was used within the model. In the physical model, no visible aerosol or droplets were seen when the vitrector was engaged at the air-fluid interface. Droplets were produced from the opening of backflush hand piece during passive fluid-air exchange. No visible aerosol was produced from the intact valved cannulas under air pressure, but droplets were seen at the beginning of fluid-air exchange when the valved cannula was defective. CONCLUSIONS: We found no evidence of visible aerosol generation during simulated vitrectomy surgery with competent valved cannulas. In the physical model, no visible aerosol was generated by the high-speed vitrector despite cutting at the air-fluid interface.

Journal Article

Liyanage, Sidath;Ramasamy, Pathma;Elhaddad, Omar;Darcy, Kieren;Hudson, Andrew;Keller, Johannes

10.1038/s41433-020-1052-4

[Title]: Assessing visible aerosol generation during vitrectomy in the era of Covid-19. [Abstract]: OBJECTIVE: To assess visible aerosol generation during simulated vitrectomy surgery. METHODS: A model comprising a human cadaveric corneoscleral rim mounted on an artificial anterior chamber was used. Three-port 25 gauge vitrectomy simulated surgery was performed with any visible aerosol production recorded using high-speed 4K camera. The following were assessed: (1) vitrector at maximum cut rate in static and dynamic conditions inside the model, (2) vitrector at air-fluid interface in a physical model, (3) passive fluid-air exchange with a backflush hand piece, (4) valved cannulas under air, and (5) a defective valved cannula under air. RESULTS: No visible aerosol or droplets were identified when the vitrector was used within the model. In the physical model, no visible aerosol or droplets were seen when the vitrector was engaged at the air-fluid interface. Droplets were produced from the opening of backflush hand piece during passive fluid-air exchange. No visible aerosol was produced from the intact valved cannulas under air pressure, but droplets were seen at the beginning of fluid-air exchange when the valved cannula was defective. CONCLUSIONS: We found no evidence of visible aerosol generation during simulated vitrectomy surgery with competent valved cannulas. In the physical model, no visible aerosol was generated by the high-speed vitrector despite cutting at the air-fluid interface. [Keywords]:

Cancer Manag Res

The Landscape of COVID-19 in Cancer Patients: Prevalence, Impacts, and Recommendations.

Cancer patients are susceptible groups to COVID-19, and risk-adjusted models show that most cancer patients have a 25-39% mortality risk if infected with COVID-19. The infection rate of SARS-CoV-2 in cancer patients in China was 0.79% (12 of 1524 patients; 95% CI, 0.31.2%). The case fatality rate of COVID-19 in the overall population ranges from 2.3 to 8.0%; among these, the case fatality rate for cancer patients is at 5.6%. In a retrospective cohort study of 28 COVID-19-infected cancer patients, a total of 15 (53.6%) patients had severe outcomes with a mortality rate of 28.6%. In a pooled analysis by Aakash et al, a 2% cancer prevalence was found among admitted patients with COVID-19. In Italy, a report shows that among the 3200 patients who died of SARS-CoV-2, 19.4% were patients with cancer. In New York, 61 (28%) cancer patients succumbed to COVID-19 with a case fatality rate of 37% (20/54) and 25% (41/164) for hematologic and solid malignancies, respectively. Impacts of COVID-19 in cancer care include interruptions of life-saving therapies, distraction effects, and diagnostic overshadowing that involve diverting attention to the pandemic rather than to cancer patients and disruptions of primary palliative care to patients due to forced quarantine. Herein, we review the landscape of COVID-19 in cancer care. We also briefly share our experience and the measures in place to protect cancer patients against COVID-19 in our center.

sars-cov-2;cancer care;high-risk;mortality

Journal Article;Review

Abdihamid, Omar;Cai, Changjing;Kapesa, Linda;Zeng, Shan

10.2147/CMAR.S272008

[Title]: The Landscape of COVID-19 in Cancer Patients: Prevalence, Impacts, and Recommendations. [Abstract]: Cancer patients are susceptible groups to COVID-19, and risk-adjusted models show that most cancer patients have a 25-39% mortality risk if infected with COVID-19. The infection rate of SARS-CoV-2 in cancer patients in China was 0.79% (12 of 1524 patients; 95% CI, 0.31.2%). The case fatality rate of COVID-19 in the overall population ranges from 2.3 to 8.0%; among these, the case fatality rate for cancer patients is at 5.6%. In a retrospective cohort study of 28 COVID-19-infected cancer patients, a total of 15 (53.6%) patients had severe outcomes with a mortality rate of 28.6%. In a pooled analysis by Aakash et al, a 2% cancer prevalence was found among admitted patients with COVID-19. In Italy, a report shows that among the 3200 patients who died of SARS-CoV-2, 19.4% were patients with cancer. In New York, 61 (28%) cancer patients succumbed to COVID-19 with a case fatality rate of 37% (20/54) and 25% (41/164) for hematologic and solid malignancies, respectively. Impacts of COVID-19 in cancer care include interruptions of life-saving therapies, distraction effects, and diagnostic overshadowing that involve diverting attention to the pandemic rather than to cancer patients and disruptions of primary palliative care to patients due to forced quarantine. Herein, we review the landscape of COVID-19 in cancer care. We also briefly share our experience and the measures in place to protect cancer patients against COVID-19 in our center. [Keywords]: sars-cov-2;cancer care;high-risk;mortality

Front Immunol

Viral Emerging Diseases: Challenges in Developing Vaccination Strategies.

In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens.

covid-19;sars-cov-2;antibody-dependent enhancement;emerging infectious diseases;epidemics;pandemics;vaccines;viruses

Journal Article;Research Support, Non-U.S. Gov't;Review

Trovato, Maria;Sartorius, Rossella;D'Apice, Luciana;Manco, Roberta;De Berardinis, Piergiuseppe

10.3389/fimmu.2020.02130

[Title]: Viral Emerging Diseases: Challenges in Developing Vaccination Strategies. [Abstract]: In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens. [Keywords]: covid-19;sars-cov-2;antibody-dependent enhancement;emerging infectious diseases;epidemics;pandemics;vaccines;viruses