ABSTRACT
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 3,260 COVID-19 patients with respiratory failure and 12,483 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 highly pleiotropic [~]0.9-Mb inversion polymorphism 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, 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.
ABSTRACT
ObjectiveTo test the hypotheses that blood concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. MethodsForty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa). Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. ResultsIn total, 21 % (n = 10) of the patients were admitted to an intensive care unit, whereas the overall mortality rate was 13 % (n = 6). Non-survivors had higher serum concentrations of NfL than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10-7) and unadjusted analyses (p = 0.001). Serum concentrations of GFAp were significantly higher in non-survivors than survivors in adjusted analyses (p = 0.02). The NfL concentrations in non-survivors increased over repeated measurements, whereas the concentrations in survivors were stable. Significantly higher concentrations of NfL were found in patients reporting fatigue, while reduced concentrations were found in patients experiencing cough, myalgia and joint pain. ConclusionIncreased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.