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.
- Zacharias, M.
- Kashofer, K.
- Wurm, P.
- Regitnig, P.
- Schütte, M.
- Neger, M.
- Ehmann, S.
- Marsh, L. M.
- Kwapiszewska, G.
- Loibner, M.
- Birnhuber, A.
- Leitner, E.
- Thüringer, A.
- Winter, E.
- Sauer, S.
- Pollheimer, M. J.
- Vagena, F. R.
- Lackner, C.
- Jelusic, B.
- Ogilvie, L.
- Durdevic, M.
- Timmermann, B.
- Lehrach, H.
- Zatloukal, K.
- Gorkiewicz, G.
Keywords
- Covid-19
- autopsy
- complement C1q
- diffuse alveolar damage
- immune exhaustion
- immune-checkpoints
- lung microbiome
- macrophages
- metatranscriptome
- secondary infections
