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Mining a GWAS of Severe Covid-19

to the Editor

Serious Kovid-19 reported by the GWAS group (15 October issue) to examine the genetic signal associated with severe coronavirus disease 2019 (Kovid-19).1 And to formulate clinically relevant hypotheses, we investigated the phenomewide associations for rs657152-A (Contribution) (See picture. S1 in Supplementary Addendum, With the full text of this paper available at

The variant rs657152-A was associated with the risks of deep-vein thrombosis and pulmonary embolism, which are widespread in patients with severe Kovid-19.2 Correlated variants were associated with high levels of blood clotting proteins von Willebrand factor and factor VIII as well as interleukin-6, which are often elevated in patients with all severe covid-19.3 Evidence from a recent study suggests that people with blood group A or type B are at greater risk for thromboembolic events than individuals with type O, regardless of Kovid-19 status.4 We have observed that high levels of the soluble lectin CD209 are associated with the single-nucleotide polymorphism rs505922-C (containing an R2 With rs657152-A) of 0.9). CD209 facilitates the proliferation of severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) in lymphocytes for T via antigen-presenting cells.5 These findings raise questions of therapeutic and pathological relevance. Can a low threshold be beneficial for the initiation of thromboprophylaxis? Is there a relationship between CD209 levels and SARS-CoV-2 viral load?

Mohammad Karim, MB, B.S.
Maya Ghusaini, Ph.D.
Welcome Sanger Institute, Hinstone, United Kingdom

Ian Dunham, D.Phil.
European Bioinformatics Institute, Hinstone, United Kingdom

No possible conflict of interest was cited relevant to this paper.

The paper was published on on November 24, 2020.

  1. 1. Gambhir Kovid-19 GWAS Group. Genomide association study of severe Kovid-19 with respiratory failure. N angle j med 2020; 383:15221534.

  2. 2. Kerbikov Obi, U Orekhov P, Borskaya Ann, Nosenko NS. High incidence of venous thrombosis in patients with moderate to severe COVID-19. June 14, 2020 ( Preprint.

  3. 3. Hemes j, Taxcard sea, Serious f, and others. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multilevel prospective cohort study. Intensive Care Made 2020; 46:10891098.

  4. 4. Great majesty, Villegas Sierra Le, Where did ma, Lipstick e, Karp JC, Van der harst pa. Genetically determined ABO blood group and its associations with health and disease. Arterioscler Thromb Vasc Biol 2020; 40:830838.

  5. 5. Jeffers SA, Tussell SM, Gillim-Ross L, and others. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natal Acad Sciences USA 2004; 101:1574815,753.

to the Editor

The severe Kovid-19 GWAS group has recently identified variants at two loci that increase the risk of respiratory failure in patients with Kovid-19. To determine the mechanisms through which these loci can withstand risk, we combined genetic data from 4856 Black and White participants and 1305 circulating proteins (with the use of SOMAScan) in three studies: the Jackson Heart Study, The Framing Heart Study, and the Malmo Diet and Cancer Study.1

Surprisingly, the specific Kovid-19 exposure version (rs657152-A) Contribution locus) was strongly associated with increased levels of CD209 antigen (also known as dendritic cell) [DC]-Special-intracellular adhesion molecule 3 [ICAM-3]-Garing nontongrene [DC-SIGN] (See Table S1 Supplementary Addendum, With the full text of this paper available at It has been found to facilitate infection by the dendritic cell-surface protein SARS-CoV-1 and other viruses.2 And can be shed into the bloodstream. Differences of cohort emerged. In the Jackson Heart Study, we found linkage between rs657152-A and several inflammatory proteins, whereas in the Framingham and Malmö studies, we found that rs657152-A was associated with adhesion protein levels. We also observed that the variant at 3p21.31 was associated with the level of CXCL16, an inflammatory chemokine implicated in alveolitis and atherogenesis (see Table S2).3,4 These analyzes suggest potential mechanisms for genetic risk in patients with Kovid-19, including proteins involved in viral binding, endothelial function, and atherothromosis.

Daniel H. Katz, MD
James G. Wilson, MD
Robert E. Gerszten, MD
Beth Israel Deaconess Medical Center, Boston, MA

For Jackson, Framingham and Malmo Heart Study Group

No possible conflict of interest was cited relevant to this paper.

The views expressed in this paper are those of the author and do not necessarily represent the views of the National Heart, Lung and Blood Institute, National Institutes of Health or the Department of Health and Human Services.

The paper was published on on November 24, 2020.

Jackson, Framingham and Malmo Heart Study Group members are listed Supplementary Addendum, Available at

  1. 1. Benson MD, Yang Q, Naga D, and others. Genetic structure of the cardiovascular risk proteome. Spreading 2018; 137:11581172.

  2. 2. Yang Zy, Huang Wai, Ganesh L, and others. The pH-dependent entry of severe acute respiratory syndrome coronaviruses is mediated by spike glycoproteins and enhanced by dendritic cell transfer via DC-SIGN. Jay Virol 2004; 78:56425650.

  3. 3. Agostini Si, Cabrel A, Calabari f, and others. Role for CXCR6 and its ligand CXCL16 in the pathogenesis of T-cell alveolitis in sarcoidosis. MJ Respiratory Crit Care Med 2005; 172:12901298.

  4. 4. Aslanian AM, Four if. Targeted dissolution of the scavenger receptor and the chemokine CXCL16 accelerates atherosclerosis. Spreading 2006; 114:583590.

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