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By Christian Hoffmann &
Bernd S. Kamps
Cantuti-Castelvetri L, Ojha R, Pedro LD, et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 2020, published 20 October. Full-text: https://doi.org/10.1126/science.abd2985
For many viruses, tissue tropism is determined by the availability of virus receptors and entry co-factors on the surface of host cells. Here, Mikael Simons, Ludovico Cantuti-Castelvetri and colleagues report that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. Another potential target for antiviral intervention.
Daly JL, Simonetti B, Klein K, et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 2020, published 20 October. Full-text: https://doi.org/10.1126/science.abd3072
Again, neuropilin-1. Step-by-step: 1) SARS-CoV-2 uses the viral Spike (S) protein for host cell attachment and entry. 2) The host protease furin cleaves the full-length precursor S glycoprotein into two associated polypeptides: S1 and S2. 3) Cleavage of S generates a polybasic Arg-Arg-Ala-Arg C-terminal sequence on S1, which conforms to a C-end rule (CendR) motif that 4) binds to cell surface neuropilin-1 (NRP1) and neuropilin-2 (NRP2) receptors. Now Yohei Yamauchi, James Daly and colleagues show that the S1 CendR motif directly binds NRP1. Blocking this interaction, using RNAi or selective inhibitors, reduced SARS-CoV-2 entry and infectivity in cell culture. NRP1 binding to the CendR peptide in S1 is thus likely to play a role in the increased infectivity of SARS-CoV-2 compared with SARS-CoV. The authors conclude that the ability to target this specific interaction might provide a route for COVID-19 therapies.
Bangaru S, Ozorowski G, Turner HL, et al. Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. Science 2020, published 20 October. Full-text: https://doi.org/10.1126/science.abe1502
Andrew Ward, Sandhya Bangaru and colleagues describe the structure of a leading SARS-CoV-2 S vaccine candidate (NVAX-CoV2373, under development by Novavax Inc. and Novavax AB, Uppsala) based on a full-length S, residues 1-1273 which includes the transmembrane (TM) and the cytoplasmic tail (CT). The authors found that NVAX-CoV2372 is stable, homogeneous, and locked in the antigenically preferred pre-fusion conformation. After structural, biophysical, and antigenic characterization, the candidate vaccine will not face the true proof-of-principle: evaluation in humans.
Azzi L. Saliva is the Key Element for SARS-CoV-2 Mass Screening. Clin Infect Dis 2020, published 21 October. Full-text: https://doi.org/10.1093/cid/ciaa1440
Saliva is the future of mass screening. In his comment on the paper by Isao Yokota et al. we presented on September 29, Lorenzo Azzi highlights the potential merits of saliva: it can be easily and non-invasively self-collected by the subject, thus avoiding the employment of skilled staff and the risk of viral transmission during the procedure, is more comfortable for the patient if compared with the nasopharyngeal swab, and for this reason is more frequently repeatable, with good compliance.
Yokota I, Shane PY, Okada K, et al. Mass screening of asymptomatic persons for SARS-CoV-2 using saliva. Clin Infect Dis. 2020 Sep 25:ciaa1388. PubMed: https://pubmed.gov/32976596. Full-text: https://doi.org/10.1093/cid/ciaa1388
We should not forget, though, that mass screening might not be easy to implement. Look at this: Pettengill MA, McAdam AJ. Can We Test Our Way Out of the COVID-19 Pandemic? J Clin Microbiol 2020, published 21 October. Full-text: https://doi.org/10.1128/JCM.02225-20
Clift AK, Keogh RH, Diaz-Ordaz K, et al. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. BMJ 2020, published 20 October. Full-text: https://doi.org/10.1136/bmj.m3731
Julia Hippisley-Cox, Ash Clift and colleagues present a new risk tool to predict a person’s risk of being admitted to hospital and dying from COVID-19. They used data from 6 million patients over a 97-day period (24 January to 30 April 2020), and a further 2.2 million patients to validate its performance over two separate time periods (24 January to 30 April 2020 and 1 May to 30 June 2020). People in the top 5% for predicted risk of death accounted for 76% of COVID-19 deaths within the 97-day study period while people in the top 20% accounted for 94% of COVID-19 deaths. We are now waiting for the model to become freely available on the internet.
See also the comment by Matthew Sperrin: Prediction models for covid-19 outcomes. BMJ 2020, published 20 October. Full-text: https://doi.org/10.1136/bmj.m3777
di Filippo L, Formenti AM, Doga M, et al. Radiological Thoracic Vertebral Fractures are highly prevalent in COVID-19 and predict disease outcomes. J Clin Endocrinol Metabol 2020, published 21 October. Full-text: https://doi.org/10.1210/clinem/dgaa738
In this retrospective cohort study from a tertiary health-care hospital in Northern Italy, 114 SARS-CoV-2 positive patients were included. Thoracic vertebral fractures (VF) were detected in 41 patients (36%). Patients with VFs required more frequently a non-invasive mechanical ventilation compared to those without VFs (p = 0.02). Mortality was 22% in VFs+ group and 10% in VFs- group (p = 0.07). In particular, mortality was higher in patients with severe VFs compared to those with moderate and mild VFs (p = 0.04). The authors conclude that VF might be a useful and easy-to-measure clinical marker of fragility and poor prognosis and suggest that morphometric thoracic vertebral evaluation should be performed in all suspected COVID-19 patients undergoing chest X-rays.
Hudowenz O, Klemm P, Lange U, et al. Case report of severe PCR-confirmed COVID-19 myocarditis in a European patient manifesting in mid January 2020. European Heart Journal – Case Reports. Full-text: https://doi.org/10.1093/ehjcr/ytaa286
A positive polymerase chain reaction (PCR) test of SARS-CoV-2 in heart specimens: the authors present a case of severe COVID-19 myocarditis manifesting in mid-January 2020. Primarily suspected of being related to small-vessel vasculitis, the case was later revised to COVID-associated disease when the patient reported a history of travel to Tyrol. Consequently, PCR testing resulted positive in a previously obtained heart specimen. The immunosuppressive treatment was discontinued. During a follow-up visit at the end of April, the patient’s recovery was stable.
Mohamed MO, Banerjee A, Clarke S, et al. Impact of COVID-19 on cardiac procedure activity in England and associated 30-day mortality. Eur Heart J 2020, published 20 October. Full-text: https://doi.org/10.1093/ehjqcco/qcaa079
A preview of what cardiology departments might see in the coming autumn and winter months 2020/2021. The authors analyzed the impact of COVID-19 on changes in cardiac procedure activity in England. Compared to the monthly averages (March-May) in 2018/2019, there was a deficit of 45,501 procedures between 1st January and 31st May 2020. Cardiac catheterization and device implantations were the most affected in terms of numbers (n = 19,637 and n = 10,453). No difference in 30-day mortality was observed between pre-COVID and COVID time-periods for all cardiac procedures except cardiac catheterization and cardiac device implantation.
Ledford H. How obesity could create problems for a COVID vaccine. Nature 2020, published 20 October. Full-text: https://www.nature.com/articles/d41586-020-02946-6
In this Nature news feature, senior science reporter Heidi Ledford describes fears of researchers that vaccines might not be as effective in people who are obese, a population already highly vulnerable to COVID-19.