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Top 10: September 8

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By Christian Hoffmann &
Bernd S. Kamps

8 September

Virology

Callaway E. The coronavirus is mutating — does it matter? Nature 2020, published 8 September. Full-text: https://www.nature.com/articles/d41586-020-02544-6

Is there evolutionary pressure on the virus to spread better? Maybe later, but not now. At a time when nearly everyone on the planet is susceptible, “every single person that it comes to is a good piece of meat (William Hanage)”. Follow Ewen Callaway on a ‘Current Knowledge Tour’ about SARS-CoV-2 mutations

‘Closed’ and ‘open’ conformations of the spike protein on SARS-CoV-2, which binds to receptors on human cells. A common mutation (circled) seems to make the protein favor open conformations, which might mean the virus can enter cells more easily. Source: Structural data from K. Shen & J. Luban. Reproduced with permission.

 

Immunology

Peng Y, Mentzer AJ, Liu G, et al. Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. Nat Immunol 2020, published 7 September. Full-text: https://doi.org/10.1038/s41590-020-0782-6

Are SARS-CoV-2-specific CD8+ T cells protective? That’s one conclusion of the paper by Tao Dong, Yanchun Peng. After studying T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, the authors found that the proportion of the T cell response attributable to CD8+ (rather than CD4+) T cells was increased in mild cases. They also report a robust and diverse T cell response targeting multiple structural and non-structural regions of SARS-CoV-2 in most resolved cases, irrespective of whether the individual had mild or severe infection (see below, Swadling + Maini 2020). The authors conclude that the identification of non-spike dominant CD8+ T cell epitopes suggests the potential importance of including non-spike proteins such as NP, M and ORFs in future vaccine designs.

See also the comment by Leo Swadling and Mala Maini: [T cells in COVID-19 — united in diversity. Nat Immunol 2020, published 7 September. Full-text: https://doi.org/10.1038/s41590-020-0798-y] they insist that careful delineation of the frequency, specificity, functionality and durability of T cells during COVID-19 is vital to understanding how to use them as biomarkers and targets for immunotherapies or vaccines.

 

Vaccine

Jeyanathan M, Afkhami S, Smaill F, et al. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol 2020, published 4 September. Full-text: https://doi.org/10.1038/s41577-020-00434-6

In this review, Zhou Xing, Mangalakumari Jeyanathan and colleagues describe the immunological principles of SARS-CoV-2 vaccine development and analyze the current vaccine candidates, their strengths and potential shortfalls. They also make inferences about their chances of success. A hazardous undertaking.

 

Diagnostics

Ogata AF, Maley AM, Wu C, et al. Ultra-sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease. Clin Chem 2020, published 8 September. Full-text: https://doi.org/10.1093/clinchem/hvaa213

We all know about SARS-CoV-2 PCR and serology tests. What about SARS-CoV-2 antigen assays? David Walt, Alana Ogata and colleagues saw the potential to identify active infection and monitor disease progression. Now they describe Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of 64 COVID-19 positive patients, 17 COVID-19 negative patients, and 34 pre-pandemic patients. They detected SARS-CoV-2 S1 and N antigens in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean of 5 ± 1 days after seroconversion. Importantly, the correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within one day) was statistically significant. SARS-CoV-2 viral antigens associated with disease progression, such as respiratory failure, in patients with COVID-19? Congratulations!

 

Crone MA, Priestman M, Ciechonska M, et al. A role for Biofoundries in rapid development and validation of automated SARS-CoV-2 clinical diagnostics. Nat Commun 11, 4464 (2020). Full-text: https://doi.org/10.1038/s41467-020-18130-3

Diagnostic testing is essential not only for the identification of infection in patients but also for tracking and containment of viral spread within communities, and daily screening of medical frontline workers. Here, Paul Freemont, Michael Crone and colleagues present a reagent-agnostic automated SARS-CoV-2 testing platform that can be quickly scaled and that is operational in two London hospitals with a testing capacity of 2000 samples per day. The authors report the performance of the overall workflow and detection of SARS-CoV-2 in patient samples using RT-qPCR, CRISPR-Cas13a, and RT-LAMP.

 

Tang MS, Case JB, Franks CE, et al. Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays. Clin Chem 2020, published 7 September. Full-text: https://doi.org/10.1093/clinchem/hvaa211

Are the results of commercially available SARS-CoV-2 serological assays correlated to the presence of neutralizing antibodies? (Remember:  methods for the detection and quantification of neutralizing antibodies are relatively low-throughput and limited to Biosafety Level 3-equipped research laboratories!) Christopher Farnsworth, Mei San Tang and colleagues looked for neutralizing antibodies to SARS-CoV-2 in specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys anti-SARS-CoV-2 (nucleocapsid), Abbott SARS-CoV-2 IgG (nucleocapsid), or EUROIMMUN (EI) SARS-CoV-2 IgG (S1) assays. They found modest correlation, but poor concordance and NPA between the Roche, Abbott and EI SARS-CoV-2 assays for the detection of SARS-CoV-2 neutralizing antibodies.

[Sentence of the day: “The emergence of commercially available serological assays for the detection of antibodies to SARS-CoV-2 has outpaced scientific understanding of their immunological meaning and their value in clinical decision making.”]

 

Clinical

Fernandes Valente Takeda C, Moura de Almeida M, Gonçalves de Aguiar Gomes R, et al. Case Report: Recurrent Clinical Symptoms of COVID-19 in Healthcare Professionals: A Series of Cases from Brazil. Am J Trop Med Hyg. 2020 Sep 4. PubMed: https://pubmed.gov/32888288. Full-text: https://doi.org/10.4269/ajtmh.20-0893

Luciano Pamplona de Góes Cavalcanti, Christianne Fernandes Valente Takeda and colleagues describe six cases of recurrent SARS-CoV-2 infection in Brazilian healthcare professionals. The time elapsed between the onset of symptoms in the two episodes ranged from 53 to 70 days. Most recurrences progressed without complications. Unfortunately, sequencing of the virus was not possible.

 

Society

Horton R. Covid-19 has exposed the reality of Britain: poverty, insecurity and inequality. The Guardian 2020, published 8 September. Full-text: https://www.theguardian.com/commentisfree/2020/sep/08/covid-19-britain-poverty-insecurity-inequality-fairer-society

Can only a fairer society can lay the foundations for economic recovery, and build resilience to future crises? Richard Horton, the Lancet Editor-in-Chief, explains why.

 

Spanish

If you read Spanish, read Zafra I. Así es la nueva escuela que debe resistir al coronavirus. El País, publicado el 6 de septiembre. Full-text: https://elpais.com/educacion/2020-09-06/asi-es-la-nueva-escuela-que-debe-resistir-al-coronavirus.html

8,2 millones de alumnos vuelven a las aulas, seis meses después del inicio del cierre escolar. Ignacio Zafra describe 7 situaciones:

  1. El camino al colegio
  2. Entrada al centro
  3. Aulas burbujas y aulas con distancia
  4. La semipresencialidad
  5. El patio, lugar seguro
  6. Un caso de COVID-19 en la escuela
  7. El comedor

 

French

If you read French, read Éditorial. Tests Covid-19 : une situation préoccupante. Le Monde 2020, publié le 7 septembre. Texte intégral : https://www.lemonde.fr/idees/article/2020/09/07/tests-covid-19-une-situation-preoccupante_6051284_3232.html

Alors que la hausse des contaminations s’accélère, l’intensification de la stratégie de dépistage des autorités a entraîné de sévères dysfonctionnements, qui montrent que l’ensemble du dispositif a atteint ses limites.