Copy-editor: Rob Camp
Treatment
* * * Paper of the Day * * *
Gottlieb RL, Chen P, Boscia J, et al. Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19. A Randomized Clinical Trial. JAMA January 21, 2021. Full-text: https://doi.org/10.1001/jama.2021.0202
Bamlanivimab and etesevimab are anti-spike neutralizing monoclonal antibodies that were derived from 2 separate patients who recovered from COVID-19 in North America and China, respectively. This RCT evaluated early treatment in 577 outpatients with mild-to-moderate COVID-19. There was no significant difference in change in viral load with 3 different doses of bamlanivimab monotherapy compared with placebo. However, treatment with a combination of bamlanivimab and etesevimab significantly decreased SARS-CoV-2 viral load by -0.57 log at day 11 compared with placebo. Further ongoing clinical trials will focus on assessing the clinical benefit.
The CORIMUNO-19 Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. Lancet Resp Med January 22, 2021. DOI:https://doi.org/10.1016/S2213-2600(20)30556-7.
Anakinra is a recombinant human IL-1 receptor antagonist. This randomized open label study from France was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia.
Cavalli G, Dagna L. The right place for IL-1 inhibition in COVID-19. Lancet Resp Med January 22, 2021. DOI:https://doi.org/10.1016/S2213-2600(21)00035-7
According to Giulio Cavalli and Lorenzo Dagna, the “impression stands that IL-1 inhibition has therapeutic rationale in COVID-19”. In their comment on the CORIMUNO trial, they argue that a true test of anakinra would be in patients with more severe COVID-19, or with evidence of IL-1-mediated hyperinflammation.
Cohen J. Monoclonal antibodies can prevent COVID-19—but successful vaccines complicate their future. Sciencemag January 22, 2021. https://www.sciencemag.org/news/2021/01/monoclonal-antibodies-can-prevent-covid-19-successful-vaccines-complicate-their-future
Some thoughts on antibodies. Now that vaccines, cheaper and easier to administer, are being deployed by the millions—with priority for the most vulnerable populations—the question is what role remains for monoclonal antibodies. One potential drawback is that these antibodies could undermine the effectiveness of vaccines. According to some experts, they might be important for the elderly and other people with compromised immune systems who do not have vigorous responses to vaccines.
Epidemiology
Quilty BJ, Clifford S, Hellewell J, et al. Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study. Lancet Public Health January 20, 2021. DOI:https://doi.org/10.1016/S2468-2667(20)30308-X
The main results of this modelling study: quarantine until a PCR or lateral flow antigen test on day 7 after exposure (with early release if negative) might avert as much transmission as a 14-day quarantine period. Additionally, daily repeated lateral flow antigen testing of traced contacts for 5 days, with isolation only after a positive test, might allow for the quarantine requirement to be removed with a small increase in transmission risk, which could itself be offset by increased participation and adherence to isolation. (A visual would be great here)
Immunology
Kusnadi A, Ramírez-Suástegui C, Fajardo V, et al. Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells. Sci Immunol. 2021 Jan 21;6(55):eabe4782. PubMed: https://pubmed.gov/33478949. Full-text: https://doi.org/10.1126/sciimmunol.abe4782
This study, using single-cell transcriptome and TCR sequence analyses of > 87.000 in vitro activated virus-reactive CD8+ T cells and > 20.000 CD8+ T cells expressing activation markers ex vivo, from a total of 39 COVID-19 patients, gives important insights into CD8 T cell responses. Findings indicate that SARS-CoV-2-reactive CD8+ T cells from patients with severe COVID-19 displayed multiple features that support the generation of robust CD8+ T cell memory responses with pro-survival properties and a lack of “restrained function” via “exhaustion” features.
Vaccine
Bubar KM, Reinholt K, Kissler SM, et al. Model-informed COVID-19 vaccine prioritization strategies by age and serostatus. Science 21 Jan 2021:eabe6959. DOI: 10.1126/science.abe6959
Mathematical models comparing five age-stratified prioritization strategies: a highly effective transmission-blocking vaccine prioritized to adults ages 20-49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults over 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact.
Fitzpatrick MC, Galvani AP. Optimizing age-specific vaccination. Science 21 Jan 2021: eabg2334. DOI: 10.1126/science.abg2334
Vaccination strategies are not one size fits all. In their perspective, Meagan C. Fitzpatrick and Alison P. Galvani looked at vaccination of different age groups. Although vaccination of younger adults is projected to avert the greatest incidence, vaccinating older adults will most effectively reduce mortality.
Pathogenesis
Hann von Weyhern C, Kaufmann I, Neff F. Neuropathology associated with SARS-CoV-2 infection – Authors’ reply. Lancet January 23, 2021. DOI:https://doi.org/10.1016/S0140-6736(21)00097-0
Lively Discussion about various hypotheses regarding COVID-19 neuropathology (the authors report a pronounced CNS involvement with pan-encephalitis, meningitis, and brainstem neuronal cell damage in a small case series).
Clinical
Ni YN, Wang T, Liang BM, Liang ZA. The independent factors associated with oxygen therapy in COVID-19 patients under 65 years old. PLoS One. 2021 Jan 22;16(1):e0245690. PubMed: https://pubmed.gov/33481912. Full-text: https://doi.org/10.1371/journal.pone.0245690. eCollection 2021
Oxygen therapy is highly required in COVID-19 patients under 65 years old who are admitted to hospital, but the success rate is high: among 833 COVID-19 patients under 65 years old, 29,4% had one or more co-morbidities. Oxygen therapy was required in 63,1%, and the mortality was only 2,9% among the oxygen therapy patients. Respiratory failure-related symptoms, elevated respiratory rate, low albumin and globulin levels, and fever at admission were independent risk factors for the requirement of oxygen.