Top 10: February 12

Copy-editor: Rob Camp


Paper of the Day

Woolhandler S, Himmelstein DU, Ahmed S, et al. Public policy and health in the Trump era. Lancet 2021, published 10 February. Full-text:

A lesson of leadership failure.



Carrat F, Figoni J, Henny J, et al. Evidence of early circulation of SARS-CoV-2 in France: findings from the population-based “CONSTANCES” cohort. Eur J Epidemiol (2021). Full-text:

Using serum samples routinely collected in 9144 adults from a French general population-based cohort, Fabrice Carrat et al. identified 13 participants with a positive anti-SARS-CoV-2 IgG test between November 2019 and January 2020. The results were confirmed by neutralizing antibodies testing. Investigations in 11 of these participants revealed experience of symptoms possibly related to a SARS-CoV-2 infection or situations of risk of potential SARS-CoV-2 exposure. This report suggests early circulation of SARS-CoV-2 in Europe.



Brooks JT, Beezhold DH, Noti JD, et al. Maximizing Fit for Cloth and Medical Procedure Masks to Improve Performance and Reduce SARS-CoV-2 Transmission and Exposure, 2021. MMWR Morb Mortal Wkly Rep. ePub: 10 February 2021. DOI:

From half-mask to double mask – the US is trying to make up ground on the disastrous first-year management of the COVID-19 pandemic. The CDC (finally, back!) conducted experiments to assess two ways of improving the fit of medical procedure masks: fitting a cloth mask over a medical procedure mask (double masking), and knotting the ear loops of a medical procedure mask and then tucking in and flattening the extra material close to the face. Each modification substantially improved source control and reduced wearer exposure. See also Glenza J. CDC study recommends double masking to reduce Covid-19 exposure. The Guardian 2021, published 10 February. Full-text:

Graphical abstract:



Liu C, Martins AJ, Lau WW, et al. Time-resolved Systems Immunology Reveals a Late Juncture Linked to Fatal COVID-19. Cell 2021, publised 10 February. Full-text:

John Tsang, Can Liu and colleagues assessed the cell surface protein phenotype, transcriptome, and T cell clonality of peripheral immune cells of COVID-19 patients over time. They revealed a network of cell type specific signatures linked to disease severity, dissected timing effects, and uncovered a late period during which the host immune response undergoes a striking divergence in patients with distinct disease severity and outcomes. The ‘disease severity network’ pointed to attenuated inflammation and an “exhaustion”-like gene expression state in CD56dimCD16hi NK cells as a primary positive correlate of disease severity.



Zucman N, Uhel F, Descamps D, Roux D, Ricard JD. Severe reinfection with South African SARS-CoV-2 variant 501Y.V2: A case report. Clin Infect Dis 2021, published 10 February. Full-text:

Noémie Zucman, Fabrice Uhel and colleagues report a case of severe SARS-CoV-2 reinfection with South African variant 501Y.V2, four months after recovering from a first episode of COVID-19. During the first episode, in September 2020, the 58-year-old man with a history of asthma had mild fever and dyspnea; symptoms resolved within a few days. In January 2021, 129 days after onset of the first infection, he presented to hospital for recurrent dyspnea and fever. Sequencing revealed the B1351 variant. Seven days later, the patient developed a severe acute respiratory distress syndrome requiring intubation and mechanical ventilation.



Ramakrishnan S, Nicolau DV, Langford B, et al. Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial. medRxiv 2021, posted 8 February. Full-text:

Early administration of inhaled budesonide might reduce the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection. This is the result of a randomized, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild COVID-19 symptoms. The primary endpoint (COVID-19-related urgent care visit, emergency department assessment or hospitalization) occurred in 10 of 69 participants in the usual care arm and in 1 of 70 participants in the budesonide arms (p = 0,004). Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, p = 0,007). Importantly, fewer participants randomized to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Background of the study: multiple hospital cohorts have shown that patients with chronic respiratory disease are significantly under-represented. The authors hypothesize that the widespread use of inhaled glucocorticoids is responsible for this finding.


Severe COVID

Huang Z, Ning B, Yang HS, et al. Sensitive tracking of circulating viral RNA through all stages of SARS-CoV-2 infection. J Clin Invest 2021, published 9 February. Full-text:

Sensitive detection of SARS-CoV-2 RNA in blood by CRISPR-augmented RT-PCR permits accurate COVID-19 diagnosis, and can detect COVID-19 cases with transient or negative nasal swab RT-qPCR results. Tony Hu, Zhen Huang and colleagues suggest that this approach could improve COVID-19 diagnosis and the evaluation of SARS-CoV-2 infection clearance, and predict severity of infection.


Sablerolles RSG, Lafeber M, van Kempen JAL, et al. Association between Clinical Frailty Scale score and hospital mortality in adult patients with COVID-19 (COMET): an international, multicentre, retrospective, observational cohort study. Lancet Healthy Longevity 2021, published 9 February. Full-text:

In some places, the scarcity of resources has necessitated triage of critical care for COVID-19 patients. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty, measured by the Clinical Frailty Scale (CFS). Here, Roos Sablerolles et al. show that among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care, whereas mildly frail patients had no significant difference in incidence compared to fit patients. Likewise, an increased hospital mortality risk was only observed in frail patients. However, the authors caution that treatment decisions based on the CFS in patients younger than 65 years should be made with caution.



Brookman S, Cook J, Zucherman M, Broughton S, Harman K, Gupta A. Effect of the new SARS-CoV-2 variant B.1.1.7 on children and young people. Lancet Child Adolesc Health 2021, published 10 February. Full-text:

In children and young people, infection with B117 does not result in an appreciably different clinical course to the original strain. This is the result of a study that compared 20 children and young people admitted to King’s College Hospital, London, between March 1, and May 31, 2020, and 60 children and young people admitted between Nov 1, 2020, and Jan 19, 2021. Atul Gupta, Sarah Brookman and colleagues conclude that severe acute respiratory COVID-19 remains an uncommon occurrence in children and young people.



If you read French, read Foucart S. Pandémie de Covid-19 : le virus circulait sans doute en France dès novembre 2019. Le Monde 21, published 10 February. Full-text :

Les résultats des travaux de chercheurs français mettent à mal l’hypothèse d’un départ de l’épidémie sur le marché chinois de Wuhan au début du mois de décembre 2019.


Le point sur l’épidémie de Covid-19 en France : le variant britannique représente un quart des infections. Le Monde 21, published 11 February. Full-text :

Le ministre de la santé, Olivier Véran, a reconnu que la situation en Moselle est « inquiétante », car les variants sud-africain et brésilien sont « très présents ».


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