Fig. 1: Summary of the GWAS for COVID-19 severity in the Chinese population.
From: Genome-wide association study of COVID-19 severity among the Chinese population
a Analyses pipeline of this study. We performed a genome-wide association study (GWAS) on 863 severe or critical COVID-19 patients (cases) and 529 mild or moderate patients (controls) from two hospitals, Huoshenshan (HSS) and Union hospitals, Wuhan city, Hubei province, China (after quality controls). We also conducted statistical and functional fine-mapping analyses for the two loci that reached the genome-wide significance (P = 5 × 10−8). eQTL, expression quantitative trait locus. b Main findings of this study. We identified two novel loci (chromosome 11q23.3 and 11q14.2) to be significantly associated with COVID-19 severity (P < 5 × 10−8). We also replicated two loci that were previously shown to be associated with COVID-19 (i.e. ABO blood groups at 9q34.2 and dipeptidyl peptidase 9 [DPP9] at 19p13.3). c Potential biological and clinical implications in severe COVID-19 suggested by the genetic findings in this study. A recent study has shown that SARS-CoV-2 can use the endosomal cysteine proteases Cathepsin B and L (CTSB/L) and the serine protease transmembrane serine protease 2 (TMPRSS2) for cell entry (through endocytosis or membrane fusion mechanisms, respectively), and the combination use of the CTSB/L inhibitor (E64-d) and TMPRSS2 inhibitor (camostat mesylate) can fully block the entry of SARS-CoV-2 into human cells. In this study, we have suggested that CTSC, which encodes an endosomal cysteine protease, to be a candidate susceptibility gene of COVID-19 severity (index SNP rs10831496). A phase III clinical trial “STOP-COVID19” is running to evaluate whether the Cathepsin C (CTSC) inhibitor Brensocatib (DB15638) can help COVID-19 patients. In TMPRSS2 gene, we also detected a suggestive association signal (index SNP rs430915).
