Summary
Secondary 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.
【저자키워드】 immunology, Virology, Microbiome, 【초록키워드】 Macrophage, pathology, pandemic, Mortality, Immunity, SARS-COV-2 infection, myeloid cells, lung, complement, RNA-Seq, Secondary infection, Control, death, Diffuse alveolar damage, secondary infections, Bacterial, cellular, microbial, DAD, subgroup, Factor, alteration, lung tissue, organ, Defense, lethal, driving, inhibitory, dominant, highlight, significantly, reduced, contribute, cause, fungal pathogen, stratified, C1q, pathophysiological, 【제목키워드】 Secondary infection, feature,