Bui DP, McCaffrey K, Friedrichs M, et al. Racial and Ethnic Disparities Among COVID-19 Cases in Workplace Outbreaks by Industry Sector — Utah, March 6–June 5, 2020. MMWR Morb Mortal Wkly Rep. ePub: 17 August 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6933e3
We need to understand which types of work have the highest exposure risk for SARS-CoV-2. In Utah, US, from March to June 2020, approximately 12% of confirmed COVID-19 cases were associated with workplace outbreaks. The 210 workplace outbreaks occurred in 15 of 20 industry sectors; nearly half of all workplace outbreaks occurred in three sectors: Manufacturing (43; 20%), Construction (32; 15%) and the Wholesale Trade (29; 14%); 58% (806 of 1,389) of workplace outbreak-associated cases occurred in these three sectors. David Bui and colleagues recommend that mitigation strategies should be culturally and linguistically responsive to racial/ethnic minority workers disproportionately affected by COVID-19.
Addetia A, Crawford K, Dingens A, et al. Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with high attack rate. medRxiv 2020, posted 14 August. Full-text: https://doi.org/10.1101/2020.08.13.20173161
What are the immunological correlates of protection against SARS-CoV-2? The ongoing Phase III vaccine trials might provide an answer within months. In the meantime, Alexander Greninger and colleagues provide insights into the protective nature of neutralizing antibodies. Their data source? Shipping vessels, “particularly useful candidates for assessing protection from SARS-CoV-2 infection”. Here they report an outbreak of SARS-CoV-2 among 122 crewmembers with an attack rate greater than 85% – a fairly high percentage due to high population density and multiple contacts between people on ships. Preeminently, none of three individuals with pre-existing neutralizing antibodies were infected. (Their neutralizing titers [1:174, 1:161, 1:3082] were in the typical range of titers observed in humans who have been infected with SARS-CoV-2 within the previous few months.) These findings are consistent with data from animal models, in which the elicitation of high titers of neutralizing antibodies was protective against re-challenge with SARS-CoV-2. The paper has not yet been peer reviewed.
Hachim A, Kavian N, Cohen CA et al. ORF8 and ORF3b antibodies are accurate serological markers of early and late SARS-CoV-2 infection. Nat Immunol 2020, published 17 August. Full-text: https://doi.org/10.1038/s41590-020-0773-7
A broader landscape of antibody responses to a range of viral proteins may help in detecting the immunogenicity of SARS-CoV-2 infection and understanding pathogenesis and immunity. Sophie Valkenburg, Niloufar Kavian, Asmaa Hachim and colleagues used the luciferase immunoprecipitation system (LIPS) assay to assess the antibody responses to a panel of 15 SARS-CoV-2 antigens; four structural proteins (S, N, M and E), three S subunits (S1, S2 and S2′), the seven available ORFs (ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8 and ORF10) and one relevant NSP within ORF1ab (NSP1). Their data suggest that the combinational use of ORF3b, ORF8 and N may be a high-performing marker of infection at early and late time points.
Laing AG, Lorenc A, del Molino del Barrio I, et al. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat Med 2020, published 17 August. Full-text: https://doi.org/10.1038/s41591-020-1038-6
Over the coming months, we will get a clearer view of 1) correlates of immunoprotection, such as virus-specific antibodies that limit disease and 2) correlates of immune dysregulation, such as cytokine over-production that may promote disease. Adrian Hayday, Manu Shankar-Hari and colleagues now explain that collectively, those correlates can compose a core disease-associated immune signature. They identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. One set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. The immune signature is provided as a large dataset supported by an online portal, www.immunophenotype.org,
Carter MJ, Fish M, Jennings A, et al. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat Med 2020, published 18 August. Full-text: https://doi.org/10.1038/s41591-020-1054-6
Second article by Manu Shankar-Hari today. He, Shane Tibby and colleagues performed peripheral leukocyte phenotyping in 25 patients with pediatric multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2. Their data suggest that MIS-C is an immunopathogenic illness distinct from Kawasaki disease.
Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020 Aug 11;370:m3026. PubMed: https://pubmed.gov/32784198. Full-text: https://doi.org/10.1136/bmj.m3026
Up to 10% of people may experience prolonged illness after COVID-19. Trish Greenhalgh and colleagues give a thorough overview of the management of post-acute COVID-19 (“long COVID”). A must-read for all practitioners.
Trezza A, Iovinelli D, Santucci A, et al. An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors. Sci Rep 10, 13866 (2020). Full-text: https://doi.org/10.1038/s41598-020-70863-9
Until an effective vaccine is available, repurposing FDA-approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. Here Ottavia Spiga and colleagues combine molecular dynamics simulations (MD), Supervised MD (SuMD), Steered MD (SMD) and interaction energy calculations, and showed that simeprevir (an HCV drug withdrawn from the European market in 2018) and lumacaftor (used in cystic fibrosis) bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction.
Jiang L, Tang K, Levin M et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis 2020, published 17 August. Full-text: https://doi.org/10.1016/S1473-3099(20)30651-4
Children and adolescents make up only a small percent of all COVID-19 cases. However, in the past months, reports from Europe, North America, Asia, and Latin America described children and adolescents with COVID-19-associated multisystem inflammatory conditions which are both similar and distinct from other well described inflammatory syndromes in children, including Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome. In this review, Zulfiqar Bhutta and colleagues provide an overview of the epidemiology, causes, clinical features, and current treatment protocols.
Greve JE, Gambino L. ‘It is what it is’: Michelle Obama picks Trump apart in gripping DNC speech. The Guardian 2020, published 18 August. Full-text: https://www.theguardian.com/us-news/2020/aug/17/michelle-obama-democratic-convention-joe-biden
No need for comment.
Ledford H. What the immune response to COVID-19 says about the prospects for a vaccine. Nature 2020, published 17 August. Full-text: https://www.nature.com/articles/d41586-020-02400-7
Again: can the human immune system mount a lasting defense against the pandemic virus SARS-CoV-2? Read about the Common Cold Study (snorting a nostrilful of solution containing a coronavirus), cataloguing antibody and immune-cell responses, sterilizing immunity and Plans B and T.