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
Lombardy is one of the regions in Italy most affected by COVID-19. We assessed the diffusion of the virus via testing plasma anti-SARS-CoV-2 IgG antibodies in 3985 employees of 7 different hospitals, located across the Lombardy region in areas with different exposure to the epidemic. Subjects filled an anamnestic questionnaire to self-report on COVID-19 symptoms, co-morbidities, smoking, regular or smart-working, and the exposure to COVID-19-infected individuals. We show that the number of individuals exposed to the virus depended on the geographical area where the hospital was located and ranged between 3 to 43% which correlated with the incidence of COVID-19 in Lombardy. There was a higher prevalence of females than males positive for IgG, however the level of antibodies was similar, suggesting a comparable magnitude of the response. We observed 10% of IgG positive asymptomatic individuals and another 20% with one or two symptoms. 81% of individuals presenting both anosmia/ageusia and fever resulted SARS-CoV-2 infected. IgG positivity correlated with family contacts. In conclusion, the frequency of IgG positivity and SARS-CoV-2 infection is dependent on the geographical exposure to the virus and to extra-hospital exposure.