ABSTRACT
Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes. We include detailed stratified analyses based on age, sex and disease severity. In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.31 and 19q13.33 associated with severe COVID-19 with respiratory failure. These associations implicate a highly pleiotropic ~0.9-Mb 17q21.31 inversion polymorphism, which affects lung function and immune and blood cell counts, and the NAPSA gene, involved in lung surfactant protein production, in COVID-19 pathogenesis.
Subject(s)
COVID-19 , Respiratory InsufficiencyABSTRACT
There are gender differences in susceptibility and vulnerability to the Coronavirus disease 2019 (COVID-19). The S protein of coronaviruses facilitates viral entry into target cells and employs the host cellular serine protease TMPRSS2 for S protein priming. The TMPRSS2 gene expression is responsive to androgen stimulation and it could partially explain gender differences. We tested the hypothesis that men who received 5-Alpha reductase inhibitors (5ARIs) or androgen deprivation therapy (ADT) for prostate cancer could have a different susceptibility to COVID-19. We carried out an observational study on patients who were referred to our COVID-19 regional centre in Lombardy from 1st to 31st March 2020. Data from 421 patients, 137 women (32.54%) and 284 men (67.44%) with laboratory-confirmed COVID-19, were included in this report. Overall 84 patients died: 28 women (33.33%) and 56 men (66.67%). Among men, 12 patients (4.22%) reported assuming 5ARI treatment, and 6 were under ADT. Over 12 patients under 5ARIs, 3 (25%) died; 2 deaths (33%) were reported in patients under ADT. Our findings showed that only 4.22% of the overall population received 5ARI anti-androgen therapy, a percentage, which revealed to be significantly lower (P<0.0001) than what observed in Italian men aged more than 40 years (14.97%).