Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~ 0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
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.
<b><i>Background:</i></b> The COVID-19 pandemic lockdown (CPL) lead to a significant decrease in emergency admissions worldwide. We performed a timely analysis of ischemic stroke (IS) and related consultations using the telestroke TEMPiS “working diagnosis” database prior (PL), within (WL), and after easing (EL) of CPL. <b><i>Methods:</i></b> Twelve hospitals were selected and data analyzed regarding IS (including intravenous thrombolysis [intravenous recombinant tissue plasminogen; IV rtPA] and endovascular thrombectomy [EVT]) and related events from February 1 to June 15 during 2017–2020. In addition, we aimed to correlate events to various mobile phone mobility data. <b><i>Results:</i></b> Following the significant reduction of IS, IV rtPA, and EVT cases during WL compared to PL in 2020 longitudinally (<i>p</i> values <0.048), we observed increasing numbers of consultations, IS, recommendations for EVT, and IV rtPA with the network in EL over WL not reaching PL levels yet. Absolute numbers of all consultations paralleled best to mobility data of public transportation over walking and driving mobility. <b><i>Conclusions:</i></b> While the decrease in emergency admissions including stroke during CPL can only be in part attributed by patients not seeking medical attention, stroke awareness in the pandemic, and direct COVID-19 triggered stroke remains of high importance. The number of consultations in TEMPiS during the lockdown parallels best with mobility of public transportation. As a consequence, exposure to common viruses, well-known triggers for acute cerebrovascular events and other diseases, are reduced and may add to the decline in stroke consultations. Further studies comparing national responses toward the course of the COVID-19 pandemic and stroke incidences are needed.
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