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
Background: The development of thrombotic coagulopathy is frequent in COVID-19 patients, but the timing after infection, cerebral venous system involvement, treatment and outcome are uncertain.Case Presentation: We report a case of massive cerebral venous thrombosis occurring in the late phase of COVID-19 infection. Mild respiratory symptoms, without fever, started three weeks before headache and acute neurological deficits. She had no dyspnea, although she was hypoxic and with typical COVID-19 associated interstitial pneumonia. Brain CT scan showed a left parietal hypodense lesion with associated sulcal subarachnoid haemorrhage. CT angiography showed a massive cerebral vein thrombosis. An asymptomatic concomitant right internal iliac vein thrombosis was found. Both cerebral venous thrombosis and deep venous thrombosis were effectively treated with unfractionated heparin started on the day of admission, then shifted to low molecular weight heparin, with a favorable clinical course. Nasopharyngel swab, repeated twice, tested negative for SARS-CoV-2. Serological tests confirmed SARS-CoV-2 infection. Conclusions: Our case supports active surveillance and prevention of thrombotic complications associated with COVID-19, which may affect both peripheral and cerebral venous system. Early initiation of unfractionated heparin may lead to good neurological outcome.