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By Christian Hoffmann &
Bernd S. Kamps

10 May

Epidemiology

Weitz JS, Beckett SJ, Coenen AR, et al. Modeling shield immunity to reduce COVID-19 epidemic spread. Nat Med. 2020 May 7. PubMed: https://pubmed.gov/32382154. Full-text: https://doi.org/10.1038/s41591-020-0895-3

The authors propose an approach to limit transmission, which is both complementary to and intended to lessen the multifaceted costs of mitigation and suppression. The core idea is to leverage a mechanism of ‘interaction substitution’ by identifying recovered individuals who have protective antibodies and deploying them back into the community. The intention is to develop population-level ‘shield immunity’ by amplifying the proportion of interactions with recovered individuals relative to those of individuals of unknown status.

 

Immunology

Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, Levantovsky R, Malle L, Moreira A, Park MD, Pia L, Risson E, Saffern M, Salomé B, Selvan ME, Spindler MP, Tan J, van der Heide V, Gregory JK, Alexandropoulos K, Bhardwaj N, Brown BD, Greenbaum B, Gümüş ZH, Homann D, Horowitz A, Kamphorst AO, Curotto de Lafaille MA, Mehandru S, Merad M, Samstein RM, The Sinai Immunology Review Project. Immunology of COVID-19: current state of the science. Immunity (2020). Full-text: https://www.cell.com/immunity/fulltext/S1074-7613(20)30183-7

Brilliant review on the current knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death.

 

Ni L, Ye F, Cheng ML, et al. Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity 2020, May 03. Full-text: https://www.cell.com/action/showPdf?pii=S1074-7613%2820%2930181-3

SARS-CoV-2-specific humoral and cellular immunity was characterized in 14 recovered patients. Of these, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. These findings suggest that both B and T cells participate in immune-mediated protection.

 

Diagnostics

Cai XF, Chen J, Hu JL, et al. A Peptide-based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019 (COVID-19). J Infect Dis. 2020 May 8. PubMed: https://pubmed.gov/32382737. Full-text: https://doi.org/10.1093/infdis/jiaa243

A new antibody assay, based on a peptide from the S protein, which was screened out from 20 candidate peptides deduced from the genomic sequence. Using a synthetic peptide may enhance the stability and repeatability of the assay, and theoretically would be more specific. A high specificity was shown. Sensitivity was lower: in 276 infection-confirmed patients, IgG was detected in 71.4% and was higher than the detection rate of IgM (57.2%).

 

Comorbidities

Chung SC, Providencia R, Sofat R, et al. Association between Angiotensin Blockade and Incidence of Influenza in the United Kingdom. NEJM May 8, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMc2005396

Like SARS-CoV-2, influenza A viruses have been shown to use the ACE2 receptor. Using the linked electronic health care records of 5.6 million persons in the United Kingdom, authors have investigated the incidence of influenza among adults who received a prescription for an ACE inhibitor from 1998 through 2016. Main results: the use of ACE inhibitors and ARBs was associated with either no effect on the incidence of influenza or a lower incidence.

 

Clinical

Creel-Bulos C, Hockstein M, Amin N, Melhem S, Truong A, Sharifpour M. Acute Cor Pulmonale in Critically Ill Patients with Covid-19. N Engl J Med. 2020 May 6. PubMed: https://pubmed.gov/32374956. Full-text: https://doi.org/10.1056/NEJMc2010459

Five patients from Atlanta, USA, with profound hemodynamic instability due to the development of acute cor pulmonale. Although acute pulmonary thromboembolism was the most likely cause of right ventricular failure in these patients (4/5 were younger than 65 years of age), this was not definitively confirmed in all cases.

 

Wichmann D, Sperhake JP, Lutgehetmann M, et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med. 2020 May 6. PubMed: https://pubmed.gov/32374815. Full-text: https://doi.org/10.7326/M20-2003

Autopsy findings from 12 COVID-19 patients who died in Hamburg, Germany. Seven of the twelve had deep vein thrombosis, and pulmonary embolism was the direct cause of death in four cases. Of note, viremia was found in 6 of 10 patients tested and 5/12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.

 

Ong SW, Young BE, Leo YS. Association of higher body mass index (BMI) with severe coronavirus disease 2019 (COVID-19) in younger patients. Clinical Infectious Diseases 2020, May 8. Full-text: https://doi.org/10.1093/cid/ciaa548

Retrospective analysis of 182 patients from Singapore. Among those aged <60 years, a BMI ≥25 was significantly associated with pneumonia on chest radiograph on admission (p value = 0.017), requiring low-flow supplemental oxygen (OR 6.32, 95% CI 1.23 – 32.34) and mechanical ventilation (OR 1.16, 95% CI 1.00 – 1.34).

 

Treatment

Cohen J. The race is on for antibodies that stop the new coronavirus.  Science  08 May 2020: Vol. 368, Issue 6491, pp. 564-565. https://science.sciencemag.org/content/368/6491/564

Great overview about antibodies as a potential treatment. Many researchers are optimistic that these antibodies will, relatively quickly, prove their worth as a preventive or as a remedy that buys the world some time until a vaccine arrives (if it does). The main questions will be the capacity to manufacture at scale, distribute, and the cost.

 

Wrapp D, De Vlieger D, Corbett KS, et al. Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies. Cell. 2020 Apr 29. pii: S0092-8674(20)30494-3. PubMed: https://pubmed.gov/32375025. Full-text: https://doi.org/10.1016/j.cell.2020.04.031

Here is one. In addition to conventional antibodies, camelids also produce heavy-chain-only antibodies (HCAbs), which contain a single variable domain (VHH) instead of two variable domains (VH and VL) that make up the equivalent antigen-binding fragment (Fab) of conventional immunoglobulin G (IgG) antibodies. These so-called ‘nanobodies’ have several potential therapeutic advantages, including increased stability and ease of production. Using llamas immunized with prefusion-stabilized betacoronavirus spike proteins, the authors identified neutralizing cross-reactive VHH camelid antibodies, which may serve as potential therapeutic candidates. Crystal structures further reveal how these antibodies bind to spike proteins to prevent viral entry into cells.