Xie Y, Bowe B, Maddukuri G, et al. Comparative evaluation of clinical manifestations and risk of death in patients admitted to hospital with covid-19 and seasonal influenza: cohort study. BMJ 15 December 2020; 371. Full-text: https://doi.org/10.1136/bmj.m4677
Is COVID-19 a flu (no)? Or is it more severe and deadly than seasonal influenza (yes)? Yan Xie and colleagues have compared patients admitted to hospital with COVID-19 between 1 February 2020 and 17 June 2020 (n = 3641) and seasonal influenza between 2017 and 2019 (n = 12.676). COVID-19 was associated with higher risk of acute kidney injury (odds ratio 1.52), incident renal replacement therapy (4.11), severe septic shock (4.04), vasopressor use (3.95), pulmonary embolism (1.50), deep venous thrombosis (1.50), stroke (1.62), acute myocarditis (7.82), arrythmias and sudden cardiac death (1.76). Compared with seasonal influenza, COVID-19 was also associated with higher risk of death (HR 4.97), mechanical ventilator use (4.01), and admission to intensive care (2.41). You may use this data for discussions with COVID-19 deniers (meh, they won’t believe you anyway).
Brauner JM, Mindermann S, Sharma Mm et al. Inferring the effectiveness of government interventions against COVID-19. Science 15 Dec 2020: eabd9338. Full-text: https://science.sciencemag.org/content/early/2020/12/15/science.abd9338
Jan M. Brauner and colleagues from Oxford evaluated the impact of several NPIs on the epidemic’s growth in 34 European and 7 non-European countries by using a Bayesian hierarchical model. Good to know during these days of a second lockdown: closing all educational institutions, limiting gatherings to 10 people or less, and closing face-to-face businesses each reduced transmission considerably. Interestingly, the additional effect of stay-at-home orders was comparatively small.
Poustchi H, Darvisshiaqan M, Mohammadi Z, et al. SARS-CoV-2 antibody seroprevalence in the general population and high-risk occupational groups across 18 cities in Iran: a population-based cross-sectional study. Lancet Infect Dis December 15, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30858-6
Seroprevalence is likely to be much higher than the reported prevalence of COVID-19 based on confirmed COVID-19 cases in Iran. The overall population weight-adjusted and test performance-adjusted prevalence of antibody seropositivity in the general population was 17.1% (95% CI 14.6–19.5). Despite high seroprevalence in a few cities, a large proportion of the population is still uninfected.
Rha MS, Jeong HW, Ko JH, et al. PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19. Immunity December 10, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.12.002
Min-Seok Rha and collegues from Korea detected SARS-CoV-2-specific CD8+ T cells using MHC class I multimers and investigated their ex vivo phenotypes in peripheral blood mononuclear cells (PBMCs) from acute and convalescent COVID-19 patients. Notably, SARS-CoV-2-specific memory CD8+ T cells from convalescent patients exhibited a high proliferative capacity, but IFN-γ was produced by less than half of the SARS-CoV-2-specific memory CD8+ T cell population. The authors also demonstrated that PD-1-expressing SARS-CoV-2-specific CD8+ T cells from acute and convalescent patients were not exhausted, but activated and functional. PD-1 expression on CD8+ T cells likely reflects activation, rather than exhaustion, in COVID-19.
Jørgensen J, Holter M, Christensen JC, et al. Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19. Sci Rep 10, 21697 (2020). Full-text: https://doi.org/10.1038/s41598-020-78710-7
For this Norwegian COVID-19 cohort study, plasma cytokine levels at admission and follow-up during the first ten days of hospitalization were related to disease severity. A broad network of pro-inflammatory cytokines was elevated in plasma, especially pronounced in severe cases. Although the authors “did not find convincing evidence of a true cytokine storm”, combinations of IL-6 and MCP-1 may be further explored as potential biomarkers in severe COVID-19 infection.
Zang R, Case JB, Yutuc E, et al. Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion. PNAS December 15, 2020 117 (50) 32105-32113; first published November 25, 2020. Full-text: https://doi.org/10.1073/pnas.2012197117
Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, Ruochen Zang from St. Louis and colleagues identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of SARS-CoV-2 replication. Internalized 25HC accumulates in the late endosomes and potentially restricts SARS-CoV-2 spike protein catalyzed membrane fusion via blockade of cholesterol export. Data suggest a unifying model in which 25HC results in a redistribution of cholesterol and inhibits both endosomal entry and plasma membrane fusion, which potentially explains the CH25H inhibitory activity against wild-type SARS-CoV-2.
Chen Z, Ruan P, Wang L, Nie X, Ma X, Tan Y. T and B cell epitope analysis of SARS-CoV-2 S protein based on immunoinformatics and experimental research. J Cell Mol Med. 2020 Dec 15. PubMed: https://pubmed.gov/33325143 . Full-text: https://doi.org/10.1111/jcmm.16200
The authors used immunoinformatics to identify conservative B and T cell epitopes for S proteins of SARS-CoV-2, which might play roles in the initiation of SARS-CoV-2 infection. They identified the B cell and T cell peptide epitopes of S protein and their antigenicity, as well as the interaction between the peptide epitopes and human leucocyte antigen (HLA).
Rid A, Lipsitch M, Miller FG, et al. The Ethics of Continuing Placebo in SARS-CoV-2 Vaccine Trials. JAMA December 14, 2020. Published online December 14, 2020. Full-text: https://doi.org/10.1001/jama.2020.25053
Participants who received placebo in the vaccine trials have made an essential contribution to testing vaccine safety and efficacy. This important viewpoint argues that given limited vaccine supply for at least several months, only the participants receiving placebo who would be eligible for vaccination outside the trial should be offered access to the vaccines at this point. What did the informed consent say? Did it contemplate a EUA or other vaccines getting to market before their specific trial finishes?
Wang W, Wu Q, Yang J, et al. Global, regional, and national estimates of target population sizes for covid-19 vaccination: descriptive study. BMJ 15 December 2020; 371. Full-text: https://doi.org/10.1136/bmj.m4704
For the record: The adult population willing to be vaccinated is estimated at 3.7 billion (95% confidence interval 3.2 to 4.1 billion).
Huskamo HA, Busch AB, Uscher-Pines, et al. Treatment of Opioid Use Disorder Among Commercially Insured Patients in the Context of the COVID-19 Pandemic. JAMA December 15. 2020; 324(23):2440-2442. Full-text: https://doi.org/10.1001/jama.2020.21512
During the first 3 months of the pandemic, among patients already receiving OUD medication, there was no decrease in medication fills or clinician visits.
Liondan CE, Mankad K, Ram D. Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study. Lancet Child Adol December 15, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30362-X
An international call for cases of children with encephalopathy related to SARS-CoV-2 infection and abnormal neuroimaging findings was made. In total, 38 cases from 8 different countries reviewed by a central neuroradiology panel. The most common imaging patterns were post-infectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients).
Copy-editor: Rob Camp