Host and microbiome features of secondary infections in lethal covid-19
Martin Zacharias, Karl Kashofer, Philipp Wurm, Peter Regitnig, Moritz Schütte, Margit Neger, Sandra Ehmann, Leigh M. Marsh, Grażyna Kwapiszewska, Martina Loibner, Anna Birnhuber, Eva Leitner, Andrea Thüringer, Elke Winter, Stefan Sauer, Marion J. Pollheimer, Fotini R. Vagena, Carolin Lackner, Barbara Jelušić, Lesley A. Ogilvie, Marija Durdević, Bernd Timmermann, Hans Lehrach, Kurt Zatloukal, Gregor Gorkiewicz
Abstract
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.