New susceptibility loci for severe COVID-19 by detailed GWAS analysis in European populations (preprint)

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.

Structured ICU Resource Management in a Pandemic is Associated with Good Outcome in Critically Ill COVID-19 Patients (preprint)

Introduction: On February 25 th , 2020, the first two patients were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Tyrol, Austria. Based on alarming reports from the neighboring region Lombardy in Italy, rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease 2019 (COVID-19) patients. Methods: A coordinated county wide step-up approach ensured adequate ICU bed availability for COVID-19 patients avoiding shortage of mechanical ventilation capacity. All patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the region of Tyrol, Austria were recorded in the Tyrolean COVID-19 Intensive Care Registry. Data were censored on July 17 th , 2020. Results: From March 9 th , 2020 to July 17 th , 2020, 106 critically ill patients with COVID-19 were admitted to an ICU. Median age was 64 (interquartile range [IQR], 54-74) years and the majority of patients were male (76 patients [71.7%]). Median simplified acute physiology score III (SAPS III) was 56 (IQR, 49-64) points. The median duration from appearance of first symptoms to ICU admission was 8 (IQR, 5-11) days. Frequently observed comorbidities were arterial hypertension in 71 patients (67.0%), cardiovascular (45 patients [42.5%]) and renal comorbidities (21 patients [19.8%]). Invasive mechanical ventilation was required in 72 patients (67.9%), 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 (IQR, 5-31) days, median hospital LOS was 27 (IQR, 13-49) days.ICU mortality was 21.7% (23 patients), while only one patient (0.9%) died after ICU discharge on a general ward (hospital mortality 22,6%). As of July 17 th , 2020, two patients are still hospitalized, one in an ICU, one on a general ward. Conclusions: Critically ill COVID-19 patients admitted to an ICU in the region of Tyrol, Austria, showed a high severity of disease often requiring complex treatments with increased lengths of ICU- and hospital stay. Despite that, we found ICU and hospital mortality in this cohort to be remarkably low. Adaptive surge response providing sufficient ICU resources presumably has contributed to the overall favorable outcome.