Trends in mortality after a sepsis hospitalization: A nationwide prospective registry study from 2008-2021 (preprint)

Background Few studies have reported on mortality beyond one year after sepsis. We aim to describe trends in short- and long-term mortality among patients admitted with sepsis, and to identify clinical characteristics associated with mortality for improved monitoring, treatment and prognosis.Methods Patients ≥ 18 years admitted to all Norwegian hospitals (2008–2021) with a first sepsis episode were identified using Norwegian Patient Registry and International Classification of Diseases 10th Revision codes. Sepsis was classified as implicit (known infection site plus organ dysfunction), explicit (unknown infection site), or COVID-19 related sepsis. The outcome was all-cause mortality. We calculated age-standardized 30-day, 90-day, 1-, 5- and 10-year mortality for each admission year and estimated the annual percentage change with 95% confidence interval (CI). The association between clinical characteristics and all-cause mortality is reported as hazard ratios (HRs) from Cox regression.Results The study included 222,832 patients, of whom 127,059 (57.1%) had implicit, 92,928 (41.7%) had explicit, and 2,845 (1.3%) had COVID-19-related sepsis. Trends in overall age-standardized 30-day, 90-day, 1- and 5-year mortality decreased by 0.29 (95% CI -0.39 to -0.19), 0.43 (95% CI -0.56 to -0.29), 0.61 (95% CI -0.73 to -0.49) and 0.66 (95% CI -0.84 to -0.48) percent per year, respectively. The decrease was observed for all infections sites but was largest among patients with respiratory tract infections. Implicit, explicit and COVID-19-related sepsis had largely similar overall mortality, with explicit sepsis having a HR of 0.980 (95% CI 0.969 to 0.991) and COVID-19-related sepsis a HR of 0.916 (95% CI 0.836 to 1.003) compared to implicit sepsis. Patients with respiratory tract infections have somewhat higher mortality than those with other infection sites. Number of comorbidities was positively associated with mortality, but mortality varied considerably between different comorbidities. Similarly, number of acute organ dysfunctions was strongly associated with mortality, whereas the risk varied for each type of organ dysfunction.Conclusion Overall mortality has declined over the past 14 years among patients with a first sepsis admission. Existing comorbidity, site of infection, and acute organ dysfunction are characteristics associated with mortality and needs further attention to reduce the excess risk of long-term mortality.

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.