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Top 10: September 30

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By Christian Hoffmann &
Bernd S. Kamps

30 September

Epidemiology

Otte im Kampe E, Lehfeld AS, Buda Set al. Surveillance of COVID-19 school outbreaks, Germany, March to August 2020. Euro Surveill 2020;25(38):pii=2001645. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.38.2001645

Only a few and mostly small COVID-19 school outbreaks have been reported in Germany overall. Since the start of the COVID-19 pandemic and until 31 August 2020, only 48 (0.5%) of documented 8,841 outbreaks in occurred in schools and included 216 cases, suggesting that containment measures in place are sufficient to reduce spillover into the community.

 

Wilson E, Donovan CV, Campbell M, et al. Multiple COVID-19 Clusters on a University Campus — North Carolina, August 2020. MMWR Morb Mortal Wkly Rep. ePub: 29 September 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6939e3

The campus may be another story. On August 3, 2020, a North Carolina university broadly opened campus for the first time since transitioning to primarily remote learning in March. Consistent with CDC guidance at that time, steps were taken to prevent the spread of SARS-CoV-2 on campus (daily symptom checks, use of masks in all indoor common spaces and classrooms, physical distancing of ≥ 6 feet in indoor and outdoor settings). These steps were not sufficient. Within 3 weeks, 670 laboratory-confirmed cases were identified; student gatherings and congregate living settings, both on and off campus, likely contributed to the rapid spread. Bad news for students.

 

Virology

Rosas-Lemus M, Minasov G, Shuvalova L, et al. High-resolution structures of the SARS-CoV-2 2′-O-methyltransferase reveal strategies for structure-based inhibitor design. Science Signaling, September 29: Vol. 13, Issue 651, eabe1202. Full-text: https://doi.org/10.1126/scisignal.abe1202

The components of the replication-transcription complex include enzymes that regulate mRNA and genomic RNA synthesis, proofreading, and mRNA maturation. Enzymes such as nsp16 are critical for capping viral mRNAs, a tactic used by multiple RNA viruses to avoid immune detection. Monica Rosas-Lemus and colleagues performed an x-ray crystallographic study of the SARS-CoV-2 nsp16-nsp10 2′-O-methyltransferase complex, which methylates Cap-0 viral mRNAs to improve viral protein translation and to avoid host immune detection. They solved crystal structures for the methyltransferase in complex with various combinations of its methyl donor and cap structure substrates, a reaction product, and an inhibitor. These structures suggest potential treatment strategies by disrupting the formation of the active enzyme complex or blocking its catalytic activity.

 

Immunology, Vaccine

Shrock E Fujimura E, Kula T, et al. Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. Science  29 Sep 2020. Full-text: https://doi.org/10.1126/science.abd4250

More on antibody response. This study provides deep serological profiling of 232 COVID-19 patients and 190 pre-COVID-19 era controls, revealing over 800 epitopes in the SARS-CoV-2 proteome, among them 10 epitopes likely recognized by neutralizing antibodies. Pre-existing antibodies in controls recognized SARS-CoV-2 ORF1, while only COVID-19 patients primarily recognized spike and nucleoprotein. A machine learning model predicted SARS-CoV-2 exposure history with 99% sensitivity and 98% specificity. Individuals with more severe COVID-19 exhibited stronger and broader SARS-CoV-2 responses, and weaker antibody responses to prior infections.

 

Anderson EJ, Rouphael NG, Widge AT, et al. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. NEJM September 29, 2020.  Full-text: https://doi.org/10.1056/NEJMoa2028436

It was high time: a Phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥ 71 years). After the second immunization, serum neutralizing activity was detected in all participants by multiple methods and appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. Adverse events included mostly mild-to-moderate local and systemic adverse events of short duration, which occurred predominantly after the second dose.

 

Transmission

Mondelli MU, Colaneri M, Seminari E, et al. Low risk of SARS-CoV-2 transmission by fomites in real-life conditions. Lancet Infect Dis September 29, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30678-2

Some arguments that environmental contamination leading to SARS-CoV-2 transmission is unlikely to occur in real-life conditions, provided that standard cleaning procedures and precautions are enforced. The chance of transmission through inanimate surfaces is likely less frequent than hitherto recognized.

 

Clinical

Kabarriti R, Brodin P, Maron MI. Association of Race and Ethnicity With Comorbidities and Survival Among Patients With COVID-19 at an Urban Medical Center in New York. JAMA Netw Open September 25, 2020;3(9):e2019795. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.19795

Important finding: In this cohort study of 5,902 COVID­-19 patients treated at a single academic medical center in New York, survival outcomes of non-Hispanic Black and Hispanic patients were at least as good as those of their non-Hispanic White counterparts when controlling for age, sex, and comorbidities. This is critical to further understanding the observed population differences in mortality by race/ethnicity reported elsewhere, ie it’s a question of access to care?.

 

Severe COVID-19

Webb BJ, Pletan ID, Jensen P, et al. Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study. Lancet Rheumatology September 29, 2020DOI: https://doi.org/10.1016/S2665-9913(20)30343-X

Brandon Webb and colleagues propose criteria for hyperinflammation in COVID-19. Based on 299 hospitalized patients, a six-criterion additive scale was developed using the following biomarkers: fever, macrophage activation (hyperferritinemia), hematological dysfunction (neutrophil to lymphocyte ratio), hepatic injury (lactate dehydrogenase or asparate aminotransferase), coagulopathy (D dimer), and cytokinaemia (C reactive protein, interleukin-6, or triglycerides). This hyperinflammatory state, cHIS, is commonly associated with progression to mechanical ventilation and death. External validation is needed. The cHIS scale might be helpful in defining target populations for trials and immunomodulatory therapies.

 

Treatment

Martinot M, Jary A, Fafi-Kremer S, et al. Remdesivir failure with SARS-CoV-2 RNA-dependent RNA-polymerase mutation in a B-cell immunodeficient patient with protracted Covid-19. Clinical Infectious Diseases, ciaa1474, https://doi.org/10.1093/cid/ciaa1474

The occurrence of a mutation in the RdRP (D484Y) gene following failure of remdesivir (given 5 days) in a 76-year-old woman with a post-rituximab B cell immunodeficiency and persistent SARS-CoV-2 viremia. The mutation was not present before treatment.

 

Severe COVID

Hattenstone S. Michael Rosen on his Covid-19 coma: ‘It felt like a pre-death, a nothingness’. The Guardian 2020, published 30 September. Full-text: https://www.theguardian.com/books/2020/sep/30/michael-rosen-on-his-covid-19-coma-it-felt-like-a-pre-death-a-nothingness

Earlier this year, the beloved children’s writer Michael Rosen spent six weeks on a ventilator with coronavirus. He talks about the magic of the NHS, the mismanagement of the crisis and how his near-death experience has changed him

 

Pediatrics

Viner RM, Mytton OT, Bonell C, et al. Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults. A Systematic Review and Meta-analysis. JAMA Pediatr. September 25, 2020. Full-text: https://doi.org/10.1001/jamapediatrics.2020.4573

In this systematic review and meta-analysis including 32 studies, children and adolescents younger than 20 years had 44% lower odds of secondary infection with SARS-CoV-2 compared with adults 20 years and older; this finding was most marked in those younger than 10-to-14 years. This estimate did not change much when only medium-quality or high-quality studies were examined, although power was reduced and significance was attenuated. However, most studies were undertaken when strict social distancing measures had been introduced such as closures of schools and data were insufficient to conclude whether transmission of SARS-CoV-2 by children is lower than by adults.

 

French

If you read French, read Roucaute D. Le port du masque permet-il de s’immuniser contre le Covid-19 ? Le Monde 2020, published 30 September. Full-text: https://www.lemonde.fr/planete/article/2020/09/30/le-port-du-masque-permet-il-de-s-immuniser-contre-le-covid-19_6054145_3244.html

Des chercheurs avancent l’hypothèse que se couvrir le visage permet le développement de formes bénignes ou asymptomatiques de la maladie.

 

Cabut S. Covid-19 : avec les médecins de la dernière chance, à la Pitié-Salpêtrière. Le Monde 2020, published 29 September. Full-text : https://www.lemonde.fr/sciences/article/2020/09/29/covid-19-avec-les-medecins-de-la-derniere-chance-a-la-pitie-salpetriere_6053980_1650684.html

Le service de réanimation de l’hôpital parisien est spécialisé dans un système de circulation extracorporelle pour oxygéner le sang, l’ECMO, destiné à certains patients en état critique.