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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Zacharias, M; Kashofer, K; Wurm, P; Regitnig, P; Schütte, M; Neger, M; Ehmann, S; Marsh, LM; Kwapiszewska, G; Loibner, M; Birnhuber, A; Leitner, E; Thüringer, A; Winter, E; Sauer, S; Pollheimer, MJ; Vagena, FR; Lackner, C; Jelusic, B; Ogilvie, L; Durdevic, M; Timmermann, B; Lehrach, H; Zatloukal, K; Gorkiewicz, G.
Host and microbiome features of secondary infections in lethal covid-19.
iScience. 2022; 25(9):104926 Doi: 10.1016/j.isci.2022.104926 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Führende Autor*innen der Med Uni Graz
Gorkiewicz Gregor
Kashofer Karl
Zacharias Martin
Zatloukal Kurt
Co-Autor*innen der Med Uni Graz
Anthofer Margit
Birnhuber Anna
Durdevic Marija
Kapo Barbara
Kwapiszewska-Marsh Grazyna
Lackner Karoline
Leitner-Meyer Eva
Loibner Martina
Marsh Leigh
Pollheimer Marion
Regitnig Peter
Sauer Stefan
Vagena Fotini Rosi
Winter Elke
Wurm Philipp

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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.

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