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Host and microbiome features of secondary infections in lethal covid-19.

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.

SUBMITTER: Zacharias M

PROVIDER: S-EPMC9374491 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Host and microbiome features of secondary infections in lethal covid-19.

Zacharias Martin M Kashofer Karl K Wurm Philipp P Regitnig Peter P Schütte Moritz M Neger Margit M Ehmann Sandra S Marsh Leigh M LM Kwapiszewska Grazyna G Loibner Martina M Birnhuber Anna A Leitner Eva E Thüringer Andrea A Winter Elke E Sauer Stefan S Pollheimer Marion J MJ Vagena Fotini R FR Lackner Carolin C Jelusic Barbara B Ogilvie Lesley L Durdevic Marija M Timmermann Bernd B Lehrach Hans H Zatloukal Kurt K Gorkiewicz Gregor G

iScience 20220813 9

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 ...[more]

PMID: 35992303

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Project description:BackgroundThe mortality risk of co-infections/secondary infections (CoI/ScI) is under-reported in patients with non-critical COVID-19, leading to the under-management of CoI/ScI and publication bias in the medical literature. We aimed to investigate the association between CoI/ScI and mortality in patients hospitalised with mild-to-severe COVID-19.MethodsWe conducted a retrospective cohort study at a COVID-19 treatment hospital in Vietnam and collected all eligible medical records, with CoI/ScI status as the exposure (non-CoI/ScI and CoI/ScI, with the latter including nature of pathogen [bacterial, fungal, or bacterial + fungal] and multidrug-resistance pathogen [no MDRp or ≥ 1 MDRp]). The outcome was all-cause mortality, defined as in-hospital death by all causes or being discharged under critical illness. We used time-dependent analysis to report rates of mortality with 95% confidence intervals (95% CI, Poisson regression) and hazard ratios (HR) with 95% CI (Cox proportional hazards regression with Holm's method for multiplicity control).ResultsWe followed 1466 patients (median age 61, 56.4% being female) for a median of 9 days. We recorded 387 (26.4%) deaths (95/144 [66.0%] in the CoI/ScI group and 292/1322 [22.1%] in the non-CoI/ScI group). Adjusted mortality rates (per 100 person-days) of the CoI/ScI (6.4, 95% CI 5.3 to 7.8), including bacterial (8.0, 95% CI 7.2 to 8.9), no MDRp (5.9, 95% CI 4.8 to 7.4), and ≥ 1 MDRp (9.0, 95% CI 8.2 to 10.0) groups were higher than that of the non-CoI/ScI group (2.0, 95% CI 1.8 to 2.2). These corresponded to higher risks of mortality in the overall CoI/ScI (HR 3.27, 95% CI 2.58 to 4.13, adjusted p < 0.001), bacterial CoI/ScI (HR 3.79, 95% CI 2.97 to 4.83, adjusted p < 0.001), no MDRp CoI/ScI (HR 3.13, 95% CI 2.42 to 4.05, adjusted p < 0.001), and ≥ 1 MDRp CoI/ScI group (HR 3.89, 95% CI 2.44 to 6.21, adjusted p < 0.001). We could not attain reliable estimates for fungal and bacterial + fungal CoI/ScI.ConclusionCompared with the non-CoI/ScI group, patients with CoI/ScI had a significantly higher risk of all-cause mortality, regardless of resistance status. More evidence is needed to confirm the mortality risks in patients with fungal or bacterial + fungal CoI/ScI.

Dataset Information

Host and microbiome features of secondary infections in lethal covid-19.

Publications

Host and microbiome features of secondary infections in lethal covid-19.

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