Top 10: September 17

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By Christian Hoffmann &
Bernd S. Kamps

17 September

Epidemiology / Immunology

Ng DL, Goldgof GM, Shy BR, et al. SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood. Nat Commun 11, 4698 (2020).

In April 2020, SARS-CoV-2 seroprevalence was low in the San Francisco Bay Area (0.26% in 387 hospitalized patients; 0.1% in 1,000 blood donors). Charles Y. Chiu, Dianna Ng and colleagues also describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3–11.0 days for these 3 assays. The authors provide evidence that seropositive results using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.



Shannon A, Selisko B, Le N. Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis. Nat Commun 11, 4682 (2020).

The SARS-CoV-2 RNA-dependent-RNA-polymerase (RdRp) is a promising therapeutic target for polymerase inhibitors. Here, Bruno Canard, Ashleigh Shannon and colleagues propose that favipiravir could exert an antiviral effect through lethal mutagenesis. They also suggest that the RdRp complex might be an Achilles heel for SARS-CoV-2. Hopefully SARS-CoV-2 has more than just one Achilles heel.



Adam DC, Wu P, Wong JY, et al. Clustering and superspreading potential of SARS-CoV-2 infections in Hong Kong. Nat Med (2020). Full-text:

Dillon Adam, Peng Wu and colleagues identified 4–7 superspreading events (SSEs) across 51 clusters (n = 309 cases) and estimate that 19% (95% confidence interval, 15–24%) of cases seeded 80% of all local transmissions. After controlling for age, transmission in social settings was associated with more secondary cases than households when controlling for age. Social settings are likely to become major battle grounds of coming SARS-CoV-2 waves.



Edridge AWD, Kaczorowska J, Hoste ACR, et al. Seasonal coronavirus protective immunity is short-lasting. Nat Med (2020).

If you nurture the secret hope that SARS-CoV-2 immunity will be long-lasting, read this paper by Lia van der Hoek, Arthur Edridge and colleagues. They monitored healthy individuals for more than 35 years, measuring increases in antibodies to the structural coronavirus capsid protein for each seasonal coronavirus (HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1). Reinfection with the same seasonal coronavirus occurred frequently by 12 months after infection.


Huang AT, Garcia-Carreras B, Hitchings MDT, et al. A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity. Nat Commun 11, 4704 (2020).

Derek A. T. Cummings, Angkana Huang and colleagues review the scientific literature on antibody immunity to coronaviruses and propose 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. Your 12-page review for the weekend.



Joung J, Ladha A, Saito M, et al. Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing. N Engl J Med 2020, published 16 September. Fulltext:

CRISPR (clustered regularly interspaced short palindromic repeats)–based diagnostic tests are en vogue. Now Feng Zhang, Julia Joung and colleagues describe a simple SARS-CoV-2 test that combines simplified extraction of viral RNA with isothermal amplification and CRISPR-mediated detection. You’ll get the results in an hour with minimal equipment. First results (n = 202+/200-): sensitivity 93.1%, specificity 98.5%.


Guglielmi G. Fast coronavirus tests: what they can and can’t do. Nature 2020, published 16 September. Full-text:

Rapid antigen tests are designed to tell in a few minutes whether someone is infectious. Will they be game changers?


Guglielmi G. ‘We didn’t model that people would go to a party if they tested positive’. Nature 2020, published 11 September. Full-text:

Develop an RNA-based saliva test, deploy scalable testing as part of a campus’s effort to reopen as safely as possible, and build a model to figure out how the epidemic might evolve on the campus. If you forget to model that some people might choose to go to a party although they know that they are positive, your model won’t work. Listen to chemist Martin Burke.


Collateral Effects

Evans ML, Lindauer M, Farrell ME. A Pandemic within a Pandemic — Intimate Partner Violence during Covid-19. N Engl J Med 2020, published 16 September. Full-text:

Stay-at-home orders led to many workers being furloughed, laid off, or told to work from home. They also left many intimate partner violence victims trapped with their abusers. Megan Evans, Margo Lindauer and Maureen Farrell put the 2020 lockdown experiences into perspective.



Rubin EJ, Baden LR, Morrissey S. Operation Warp Speed and Covid-19 Therapeutics. Audio interview (25:54). N Engl J Med 2020; 383:e92. Access:

The editors look beyond Operation Warp Speed’s work in SARS-CoV-2 vaccine development to its investigation of new preventive and therapeutic agents.



If you read Spanish, read Grasso D, Zafra M, Ferrero B, et al. Covid de ricos, covid de pobres: las restricciones de la segunda ola exponen las desigualdades de Madrid. El País 2020, published 17 September. Full-text:

Daniele Grasso, Mariano Zafra, Berta Ferrero, Miguel Cantón, Fernando Peinado y Juan Diego Quesada explican que el número de contagios es mayor en las zonas más vulnerables, donde más pesarán las posibles limitaciones.