摘要：SummarySecondary infections contribute significantly to covid-19 mortality but driving factors remain poorly understood. Autopsies of 20 covid-19 cases and 14 controls from the first pandemic wave complemented with microbial cultivation and RNA-seq from lung tissues enabled description of major organ pathologies and specification of secondary infections. Lethal covid-19 segregated into two main death causes with either dominant diffuse alveolar damage (DAD) or secondary pneumonias. The lung microbiome in covid-19 showed a reduced biodiversity and increased prototypical bacterial and fungal pathogens in cases of secondary pneumonias. RNA-seq distinctly mirrored death causes and stratified DAD cases into subgroups with differing cellular compositions identifying myeloid cells, macrophages and complement C1q as strong separating factors suggesting a pathophysiological link. Together with a prominent induction of inhibitory immune-checkpoints our study highlights profound alterations of the lung immunity in covid-19 wherein a reduced antimicrobial defense likely drives development of secondary infections on top of SARS-CoV-2 infection.Graphical abstractDisplay OmittedHighlights•Covid-19 autopsy cohort complemented with microbial cultivation and deep sequencing•Major death causes stratify into DAD and secondary pneumonias•Prototypical bacterial and fungal agents are found in secondary pneumonias•Macrophages and C1q stratify DAD subgroups and indicate immune impairment in lungsImmunology; Virology; Microbiome
