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Top 10: October 8

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By Christian Hoffmann &
Bernd S. Kamps

8 October

Epidemiology

Editors. Dying in a Leadership Vacuum. N Engl J Med 2020; 383:1479-1480. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMe2029812

SARS-CoV-2 and the COVID-19 pandemic became a test of leadership. With no good options to combat a novel pathogen, countries were forced to make hard choices about how to respond. In the United States, the leaders have failed that test.

 

Transmission

Wang L, Didelot X, Yang J, et al. Inference of person-to-person transmission of COVID-19 reveals hidden super-spreading events during the early outbreak phase. Nat Commun 11, 5006 (2020). Full-text: https://doi.org/10.1038/s41467-020-18836-4

Super-spreading events are an important phenomenon in the transmission of many diseases (such as SARS-CoV-1, MERS-CoV, Ebola virus, etc.), in which certain individuals infect a disproportionately large number of people. Here Yuhai Bi, Liang Wang and colleagues show that super-spreading events played an important role in the early stage of the COVID-19 outbreak. They estimated the dispersion parameter to be 0.23 (95% CI: 0.13–0.39). (What is the dispersion parameter? Check this FT article: To beat Covid-19, find today’s superspreading ‘Typhoid Marys’)

 

Prevention

Peeples L. Face masks: what the data say. Nature 2020, published 6 October. Full-text: https://www.nature.com/articles/d41586-020-02801-8

Face coverings save lives, either by preventing SARS-CoV-2 infection or by reducing the viral infectious load. They are not infallible (so keep your distance!), but a profoundly important pillar of pandemic control. Why is the debate still going on? Read this Nature news feature by Lynne Peeples.

 

Immunology

Lipsitch M, Grad YH, Sette A, Crotty S. Cross-reactive memory T cells and herd immunity to SARS-CoV-2. Nat Rev Immunol (2020). https://doi.org/10.1038/s41577-020-00460-4

It is not clear if cross-reactive T cell memory (which largely originates from previous exposure to circulating common cold coronaviruses) affects COVID-19 disease severity in SARS-CoV-2 infected individuals. In this Perspective article, the authors reflect on the immunological and epidemiological aspects and implications of pre-existing cross-reactive immune memory to SARS-CoV-2.

 

Pathogenesis

Nienhold R, Ciani Y, Koelzer VH, et al. Two distinct immunopathological profiles in autopsy lungs of COVID-19. Nat Commun 11, 5086 (2020). https://doi.org/10.1038/s41467-020-18854-2

Immune responses in the lungs of deceased COVID-19 patients remain poorly characterized. Here, the authors describe two immunopathological patterns in the lungs of fatal COVID-19 patients based on ISG (interferon stimulated genes) expression:

Pattern 1

  • high local expression of interferon stimulated genes (ISGhigh) and cytokines
  • high viral loads
  • limited pulmonary damage

Pattern 2

  • severely damaged lungs
  • low ISGs (ISGlow), low viral loads
  • abundant infiltrating activated CD8+ T cells and macrophages.

ISGhigh patients died significantly earlier after hospitalization than ISGlow patients.

 

Vaccine

McAuley AJ, Kuiper MJ, Durr PA, et al. Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein. npj Vaccines 5, 96 (2020). https://doi.org/10.1038/s41541-020-00246-8

The D614G mutation of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of vaccines. In this article, S. Vasan, Alexander McAuley and colleagues claim that there is no experimental evidence to support this speculation. They performed virus neutralization assays using sera from ferrets that received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation.

 

Clinical

Liotta EM, Batra A, Clark JR, et al. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Ann Clin Transl Neurol. 2020 Oct 5. PubMed: https://pubmed.gov/33016619. Full-text: https://doi.org/10.1002/acn3.51210

Is encephalopathy independently associated with higher mortality in hospitalized patients with COVID-19? That’s the conclusion of a study of 509 consecutive patients admitted within a hospital network in Chicago between 5 March and 6 April 2020. The increased mortality, independent of respiratory severity, parallels previous reports about sepsis‐associated encephalopathy and delirium‐associated mortality. The authors recognize the limitations of a retrospective study. Keep an eye on the subject.

 

Severe COVID

Altschul DJ, Unda SR, Benton J, et al. A novel severity score to predict inpatient mortality in COVID-19 patients. Sci Rep 10, 16726 (2020). Full-text: https://doi.org/10.1038/s41598-020-73962-9

Determining which patients are at high risk of severe illness or mortality is essential for appropriate clinical decision making. By analyzing the date from 4711 SARS-CoV-2 infected patients, the authors developed a COVID-19 severity score ranging from 0 to 10, consisting of age, oxygen saturation, mean arterial pressure, blood urea nitrogen, C-reactive protein, and the international normalized ratio. The probability of mortality was 11.8%, 39% and 78% for patients with either a low (0–3), moderate (4–6) or high (7–10) COVID-19 severity score.

 

Education

Rubin EJ, Baden LR, Morrissey S. Covid-19 and the President. Audio interview (24.58). N Engl J Med 2020; 383: e104. Access: https://doi.org/10.1056/NEJMe2031183

The editors discuss treatments Trump has reportedly received for COVID-19, the rationale for them, and what is known about the risks and benefits.

 

Press

Gee A. Texas doctor, 28, dies of Covid: ‘She wore the same mask for weeks, if not months’. The Guardian 2020, published 7 October. Full-text: https://www.theguardian.com/us-news/2020/oct/07/texas-doctor-adeline-fagan-covid-coronavirus

Adeline Fagan tested positive in early July and died in September – as US health workers lost to COVID skew younger and lack protective equipment.

 

Spanish

If you read Spanish, read Menárguez AT. Dilema en los colegios con los aerosoles: ¿pasar frío o riesgo de contagio? El País 2020, published 8 October. Full-text: https://elpais.com/educacion/2020-10-07/dilema-en-los-colegios-con-los-aerosoles-pasar-frio-o-riesgo-de-contagio.html

Abrir las ventanas todo el día es la única guía para protegerse en las aulas de la transmisión por vía aérea. No hay protocolos específicos para el invierno (¡!).