Microbiome and host features of secondary infections in lethal COVID-19.. COVID19_Autopsy_Study

Secondary infections contribute significantly to covid-19 mortality but host and microbial factors driving this sequel remain poorly understood. We performed an autopsy study of 20 covid-19 cases and 14 controls from the first pandemic wave. Autopsies combined with microbial cultivation and deep RNA sequencing allowed us to define major organ pathologies and specify secondary infections. Lethal covid-19 segregated into two major death causes separating cases with either dominant diffuse alveolar damage (DAD) or secondary infections of lungs. Lung microbiome changes were profound in covid-19 indicating a reduced biodiversity and increased presence of prototypical bacterial and fungal pathogens in cases with secondary infections. Deep RNAseq of lung tissues clearly mirrored death categories and cellular deconvolution stratified DAD cases into subgroups with different cellular compositions. As strong separating elements we found myeloid cells including macrophages and complement C1q suggesting a pathophysiological link of these factors, indicative for induction of immune tolerance in DAD subgroups. In addition, other signatures of immuno-suppression were evident in covid-19 lungs including induction of inhibitory immune-checkpoints. Thus, our study highlights several pillars of immune-impairment in covid-19 lungs likely dampening antimicrobial defense and supporting the development of secondary infections.