Genetic characteristics involved in COVID‐19 severity. The CARGENCORS case‐control study and meta‐analysis

Abstract

AbstractPre‐existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID‐19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID‐19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID‐19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS‐CoV‐2 [COVID‐19] virus) is an age‐ and sex‐matched case‐control study with 818 COVID‐19 cases hospitalized with hypoxemia, and 1636 controls with COVID‐19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID‐19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta‐analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID‐19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID‐19 and virus infectivity. The meta‐analysis showed five SNVs associated with severe COVID‐19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID‐19 severity in the CARGENCORS data. In the meta‐analysis, five SNVs were significantly associated to COVID‐19 severity, one of them previously related to CAD.