Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. The minimum criterion for diagnosis of acute infection is detection of anti‐HEV antibodies, although there are scant data on IgM duration. Our aim was to assess the persistence of HEV markers after acute self‐limited hepatitis E. HEV serological tests (IgM by Mikrogen and Wantai and HEV‐Ag) and HEV RNA were carried out in two cohorts: (a) patients with prior acute hepatitis E (ALT >10 x ULN plus positive IgM ± HEV RNA) currently self‐limited and (b) 50 blood donors with positive HEV RNA. Among 25 cases of prior acute hepatitis E, after a median follow‐up of 34 months, all presented undetectable HEV RNA. However, anti‐HEV IgM remained detectable in 14 (56%) by Mikrogen, 6 (24%) by Wantai and none for HEV‐Ag. Anti‐HEV IgM tested positive in 80%‐100% within the second year and 17%‐42% over 3 years later, by Wantai and Mikrogen, respectively. Among HEV RNA‐positive donors, 12 (25%) tested positive for either IgM by Mikrogen or Wantai, 9 (18%) for both and 18 (36%) for HEV‐Ag. HEV‐Ag positivity was more likely as HEV RNA was higher (14% if <2.2 log IU/mL; 64% if RNA ≥ 3.7). Overall, HEV‐Ag performed best, with a positive predictive value of 100% and diagnostic accuracy of 57%. Anti‐HEV IgM exhibited unexpectedly long persistence after a self‐limited acute hepatitis E. HEV‐Ag had the best performance and could be especially useful in settings where HEV RNA is not available.

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.

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