Top 10: November 27

Copy-editor: Rob Camp

Treatment

WHO 20201120. WHO recommends against the use of remdesivir in COVID-19 patients. WHO 2020, published 20 November. Full-text: https://www.who.int/news-room/feature-stories/detail/who-recommends-against-the-use-of-remdesivir-in-covid-19-patients

First nail in the remdesivir coffin. On 20 November, WHO issued a conditional recommendation against the use of remdesivir (brand name: Veklury) in hospitalized patients, regardless of disease severity, as there is currently no evidence that remdesivir improves survival and other outcomes in these patients. Evidence from over 7000 patients across 4 trials suggests no important effect on mortality, need for mechanical ventilation, time to clinical improvement, and other patient-important outcomes. Happy France (see below, Covid-19 : comment Gilead a vendu son remdésivir à l’Europe)!

 

Epidemiology

Mavragani A, Gkillas K. COVID-19 predictability in the United States using Google Trends time series. Sci Rep 10, 20693 (2020). Full-text: https://doi.org/10.1038/s41598-020-77275-9

How will you monitor and forecast regional outbreaks as they happen or even before they happen? By using Google Trends. Amaryllis Mavragani and Konstantinos Gkillas from the University of Stirling in Scotland present a model that exhibits strong COVID-19 predictability. The authors conclude that Google Trends offers a solid foundation for quantitative analysis with respect to the monitoring and predictability of COVID-19 and suggest that these approaches may flatten epidemic curves, help in allocating health resources, and increase the effectiveness and preparedness of health care systems.

 

Immunology

Perez-Potti, A., Lange, J. & Buggert, M. Deciphering the ins and outs of SARS-CoV-2-specific T cells. Nat Immunol 2020, published 26 November. Full-text: https://doi.org/10.1038/s41590-020-00838-5

Marcus Buggert, André Perez-Potti and Joshua Lange comment on the paper by Nelde A, Bilich T, Heitmann JS, et al. who characterized HLA-specific peptide targets from SARS-CoV-2 in convalescent patients and identify cross-reactive epitopes which were probably induced by common cold coronaviruses in non-infected individuals [SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition. Nat Immunol 2020, published 30 September. PubMed: https://pubmed.gov/32999467. Full-text: https://doi.org/10.1038/s41590-020-00808-x]. This was one of the first studies to indicate that a more polyclonal T cell response may be critical in protection against SARS-CoV-2.

 

Pathogenesis

Wei C, Wan L, Yan Q, et al. HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry. Nat Metab 2020, published 26 November. Full-text: https://doi.org/10.1038/s42255-020-00324-0

Could high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitate ACE2-dependent entry of SARS-CoV-2? That is the statement by Hui Zhong, Congwen Wei, finding that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components and facilitates SARS-CoV-2 cellular attachment, entry and infection. SARS-CoV-2 entry is inhibited by silencing SR-B1 expression and by SR-B1 antagonists. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody inhibited HDL-enhanced SARS-CoV-2 infection.

 

Vaccine

Wang J. New strategy for COVID-19 vaccination: targeting the receptor-binding domain of the SARS-CoV-2 spike protein. Cell Mol Immunol 2020, published 26 November. Full-text: https://doi.org/10.1038/s41423-020-00584-6

Junzhi Wang comments on a study by Yang J, Wang W, Chen Z et al. [A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity. Nature 2020, published 29 July. Full-text: https://doi.org/10.1038/s41586-020-2599-8] we presented on 30 July. The authors show that a recombinant spike receptor-binding domain (RBD) protein of SARS-CoV-2 prepared from insect cells could induce a potent functional antibody response in mice, rabbits and non-human primates as early as 7 or 14 days after a single dose injection. Even one dose of the vaccine generated viral neutralizing activity. The vaccine protected non-human primates from live SARS-CoV-2 challenge 28 days after the first vaccination.

 

Clinical

Bellan M, Patti G, Hayden E, et al. Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients. Sci Rep 10, 20731 (2020). Full-text: https://doi.org/10.1038/s41598-020-77698-4

In March and April 2020, almost 30% of all patients (504/1697) hospitalized in three hospitals in Northern Italy died. In this 126-author paper by Pier Paolo Sainaghi, Mattia Bellan and colleagues, age, a diagnosis of cancer, and the baseline PaO2/FiO2 ratio were independent predictors of mortality.

 

Hubiche T, Cardo-Leccia N, Le Duff F, et al. Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic. JAMA Dermatol 2020, published 25 November. Full-text: https://doi.org/10.1001/jamadermatol.2020.4324

In this series of 40 consecutive patients with chilblain-like lesions, Thierry Passeron, Thomas Hubiche and colleagues found that none had a positive RT-PCR test, and only 12 (30%) had positive COVID-19 serologic results. Common findings included increased D-dimers, lymphocytic inflammation, vascular damage on skin biopsy results, and a significant interferon-alpha response compared with patients with PCR-positive, acute COVID-19 infection. The authors conclude that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.

 

Education

Centor R. A Primer on COVID-19 Vaccines. Audio interview (29:19).  Ann Intern Med 2020, published 24 November. Access: https://doi.org/10.7326/A19-0044

In this episode, Robert Cento discusses the COVID-19 vaccines under development with Paul Goepfert.

 

Society

Green A. A tribute to some of the doctors who died from COVID-19. Lancet 2020, published 28 November. Full-text: https://doi.org/10.1016/S0140-6736(20)32478-8

“The global COVID-19 death toll stands at more than 1·3 million. Among the lives lost have been those of healthcare workers, who have had crucial roles throughout the response. As the virus spread, many doctors provided treatment for a disease they little understood, while others contributed to accelerated research on potential treatments and vaccines. An Obituary published in The Lancet pays tribute to some of these doctors who died from COVID-19. Whilst it is not possible to honour all of the health workers who have died from COVID-19, the short obituaries serve as a tribute to the many other health workers who have died in the pandemic.”

 

French

If you read French, read Barnéoud L. Covid-19 : comment Gilead a vendu son remdésivir à l’Europe. Le Monde 2020, published 27 November. Full-text: https://www.lemonde.fr/planete/article/2020/11/27/covid-19-comment-gilead-a-vendu-son-remdesivir-a-l-europe_6061300_3244.html

Un contrat de 900 millions de dollars a été passé avec la Commission, alors même que le laboratoire Gilead connaissait les résultats négatifs d’un essai clinique de l’OMS. La France est le seul pays à ne pas avoir passé commande. 

 


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