COVID Reference

The COVID Textbook

Top 10: August 25

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By Christian Hoffmann &
Bernd S. Kamps

 

This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give it early visibility.

25 August

Virology

Wang Z, Zhang L, Wu M. Human-viral chimera: a novel protein affecting viral virulence and driving host T-cell immunity. Sig Transduct Target Ther 5, 167 (2020). Full-text: https://doi.org/10.1038/s41392-020-00272-x

All coronaviruses (CoV) known to infect humans are zoonotic, or of animal origin, with many thought to originate in bat hosts. Now Peter Daszak, Alice Latinne and colleagues analyzed their macroevolution, cross-species transmission and dispersal and present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in bats of the genus Rhinolophus. They also show that host-switching occurs more frequently and across more distantly related host taxa in alpha- than beta-CoVs, and is more highly constrained by phylogenetic distance for beta-CoVs. The authors identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance.

 

Basic Research

Zhao H, To KKW, Sze K et al. A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2. Nat Commun 11, 4252 (2020). Full-text: https://doi.org/10.1038/s41467-020-17986-9

Kwok-Yung Yuen, Hanjun Zhao and colleagues report a mouse β-defensin-4-derived antiviral peptide P9R exhibiting broad-spectrum antiviral activities against the enveloped SARS-CoV-2, MERS-CoV, SARS-CoV, A(H1N1)pdm09, A(H7N9) virus, and the non-enveloped rhinovirus. The authors suggest that the antiviral activity of P9R depends on the direct binding to viruses and the inhibition of virus-host endosomal acidification, which provides a proof of concept that virus-binding alkaline peptides can broadly inhibit pH-dependent viruses.

 

Immunology

Crooke SN, Ovsyannikova IG, Kennedy RB et al. Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome. Sci Rep 10, 14179 (2020). Published 25 August. Full-text: https://doi.org/10.1038/s41598-020-70864-8

Immunoinformatics for T cell and B cell epitopes? Here Gregory Poland, Stephen Crooke and colleagues used a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. They identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen.

 

Vaccine

Price WN 2nd, Rai AK, Minssen T. Knowledge transfer for large-scale vaccine manufacturing. Science. 2020 Aug 21;369(6506):912-914. PubMed: https://pubmed.gov/32792464. Full-text: https://doi.org/10.1126/science.abc9588

Identifying an effective SARS-CoV-2 vaccine and prove its safety in huge clinical trials is only the first step. The next step is not less challenging: manufacturing vaccines at enormous scale. In this Policy Forum, law school scholars Nicholson Price, Arti Rai and Timo Minssen explain that fast manufacturing will require not only physical capacity but also access to knowledge not contained in patents or in other public disclosures. Follow the authors on a path through the jungle of licenses, know-how transfer, hostage taking and manufacturing secrecy, and discover why large biopharmaceutical firms are now willing to share information that they might previously have viewed as providing competitive advantage.

 

Clinical

Pezzini A, Padovani A. Lifting the mask on neurological manifestations of COVID-19. Nat Rev Neurol 2020, published 28 August. Full-text: https://doi.org/10.1038/s41582-020-0398-3

Another review. Alessandro Pezzini and Alessandro Padovani present preclinical research suggesting that SARS-CoV-2 could be responsible for many neurological manifestations, and summarize the biological pathways that could underlie each neurological symptom.

 

Collateral Effects

Lee LYW, Cazier JB, Starkey T, et al. COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study. Lancet Oncol 2020, published 24 August. Full-text: https://doi.org/10.1016/S1470-2045(20)30442-3

Patients with cancer have been reported to be at increased risk of infection with SARS-CoV-2 and a more severe disease course. Here Gary Middleton, Lennard Lee and colleagues compare cancer patients with and without COVID-19 and analyses the effect of tumor features (primary subtype and stage) and patient demographics (age and sex) on the risk and trajectory of COVID-19 disease. Some results:

  1. The all-cause case–fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0.10 in patients aged 40–49 years to 0.48 in those aged 80 years and older.
  2. Patients with hematological malignancies (leukemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumors.
  3. Patients with hematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (odds ratio 2.09).

 

Amyn A Malik, Nauman Safdar, Subhash Chandir, et al. Tuberculosis control and care in the era of COVID-19. Health Policy and Planning 2020, published 24 August. Full-text: https://doi.org/10.1093/heapol/czaa109

Reports from India, China and Pakistan suggest a daily decline in tuberculosis case notification of 75–80% in the last few months with testing in Pakistan decreasing up to 80%. Is this the end of the Zero TB Initiative launched in October 2015 which aimed to create ‘islands of TB elimination’? See the six recommendations by Amyn Malik et al.

 

Society

Callaway E. The unequal scramble for coronavirus vaccines — by the numbers. Nature 2020, published 24 August. Full-text: https://www.nature.com/articles/d41586-020-02450-x

Will SARS-CoV-2 vaccines be only for the rich? Ellen Callaway shows how wealthy countries have struck deals to buy more than two billion doses of coronavirus vaccine. Find out that the UK is the world’s highest per-capita buyer, with 340 million purchased: around 5 doses for each citizen. And read more about COVAX, spearheaded by Gavi, a Geneva-based funder of vaccines for low-income countries, along with CEPI and the World Health Organization. It aims to secure 2 billion vaccine doses. One billion are for 92 low- and middle-income countries and economies (LMICS), which encompass half the world’s population.