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Gut Bacterial Dysbiosis and Instability is Associated with the Onset of Complications and Mortality in COVID-19

David Schult, Sandra Reitmeier, Plamena Koyumdzhieva, Tobias Lahmer, Moritz Middelhoff, View ORCID ProfileJohanna Erber, Jochen Schneider, Juliane Kager, Marina Frolova, Julia Horstmann, Lisa Fricke, View ORCID ProfileKatja Steiger, Moritz Jesinghaus, Klaus-Peter Janssen, View ORCID ProfileUlrike Protzer, Klaus Neuhaus, Roland M. Schmid, Dirk Haller, Michael Quante
doi: https://doi.org/10.1101/2021.10.08.463613
David Schult
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Sandra Reitmeier
2ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany
3Chair of Nutrition and Immunology, Technische Universität München, Freising, Germany
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Plamena Koyumdzhieva
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Tobias Lahmer
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Moritz Middelhoff
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Johanna Erber
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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  • ORCID record for Johanna Erber
Jochen Schneider
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Juliane Kager
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Marina Frolova
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Julia Horstmann
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Lisa Fricke
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Katja Steiger
4Institute of Pathology, Technische Universität München, Munich, Germany
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  • ORCID record for Katja Steiger
Moritz Jesinghaus
4Institute of Pathology, Technische Universität München, Munich, Germany
5Institute of Pathology, University Hospital Marburg, Marburg, Germany
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Klaus-Peter Janssen
6Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Ulrike Protzer
7Institute of Virology, Technische Universität/Helmholtz Zentrum München, Munich, Germany
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  • ORCID record for Ulrike Protzer
Klaus Neuhaus
2ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany
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Roland M. Schmid
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Dirk Haller
2ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany
3Chair of Nutrition and Immunology, Technische Universität München, Freising, Germany
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Michael Quante
1Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
8Department of Internal Medicine II, Universitätsklinikum Freiburg, Universität Freiburg, Freiburg, Germany
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  • For correspondence: michael.quante@uniklinik-freiburg.de
  • Abstract
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Abstract

Objective There is a growing debate about the involvement of the gut microbiome in COVID-19, although it is not conclusively understood whether the microbiome has an impact on COVID-19, or vice versa, especially as analysis of amplicon data in hospitalized patients requires sophisticated cohort recruitment and integration of clinical parameters. Here, we analyzed fecal and saliva samples from SARS-CoV-2 infected and post COVID-19 patients and controls considering multiple influencing factors during hospitalization.

Design 16S rRNA gene sequencing was performed on fecal and saliva samples from 108 COVID-19 and 22 post COVID-19 patients, 20 pneumonia controls and 26 asymptomatic controls. Patients were recruited over the first and second corona wave in Germany and detailed clinical parameters were considered. Serial samples per individual allowed intra-individual analysis.

Results We found the gut and oral microbiota to be altered depending on number and type of COVID-19-associated complications and disease severity. The occurrence of individual complications was correlated with low-risk (e.g., Faecalibacterium prausznitzii) and high-risk bacteria (e.g., Parabacteroides). We demonstrated that a stable gut bacterial composition was associated with a favorable disease progression. Based on gut microbial profiles, we identified a model to estimate mortality in COVID-19.

Conclusion Gut microbiota are associated with the occurrence of complications in COVID-19 and may thereby influencing disease severity. A stable gut microbial composition may contribute to a favorable disease progression and using bacterial signatures to estimate mortality could contribute to diagnostic approaches. Importantly, we highlight challenges in the analysis of microbial data in the context of hospitalization.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* shared co-first authorship.

  • Abbreviations

    AB T1
    Antibiotic therapy at the time of the first stool sampling
    AC
    Asymptomatic controls
    AKI
    Acute kidney injury
    AP
    Alkaline phosphatase [U/l]
    ARDS
    Acute respiratory distress syndrome
    Asympt.
    Asymptomatic
    COVID-19
    Corona virus disease 2019
    CRP
    C-reactive protein [mg/dl]
    FiO2
    Fraction of inspired oxygen (%)
    GGT
    Gamma-Glutamyltransferase [U/l]
    GI
    Gastrointestinal
    Hb
    Hemoglobin [g/dl]
    i.v.
    intravenous
    IBD
    Inflammatory bowel disease
    ICU
    Intensive care unit
    ICU all T
    Intensive care stay regarding all time points of stool sampling
    ICU T1
    Intensive care stay at the time of the first stool sampling
    N
    Number of patients
    n
    Number of samples
    NA
    not available
    PA
    Pressure assisted
    PC
    Pressure controlled
    PCT
    Procalcitonin [ng/ml]
    PE
    Pulmonary embolism
    Rel.
    Relative
    S.p.
    Status post
    SARS-CoV-2
    Severe acute respiratory syndrome coronavirus 2
    SC
    Symptomatic pneumonia controls
    Sig.
    Significant
    Sympt.
    Symptomatic
    T1
    First sampling time point
    T2D
    Type 2 diabetes mellitus
    Trp T
    High-sensitive troponin T [ng/ml]
    TS
    Tracheostomy
    VTE
    Venous thromboembolism
    WBC
    White blood cells counts [G/l]
    zOTU
    Zero-radiation operational-taxonomic units
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    Gut Bacterial Dysbiosis and Instability is Associated with the Onset of Complications and Mortality in COVID-19
    David Schult, Sandra Reitmeier, Plamena Koyumdzhieva, Tobias Lahmer, Moritz Middelhoff, Johanna Erber, Jochen Schneider, Juliane Kager, Marina Frolova, Julia Horstmann, Lisa Fricke, Katja Steiger, Moritz Jesinghaus, Klaus-Peter Janssen, Ulrike Protzer, Klaus Neuhaus, Roland M. Schmid, Dirk Haller, Michael Quante
    bioRxiv 2021.10.08.463613; doi: https://doi.org/10.1101/2021.10.08.463613
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    Gut Bacterial Dysbiosis and Instability is Associated with the Onset of Complications and Mortality in COVID-19
    David Schult, Sandra Reitmeier, Plamena Koyumdzhieva, Tobias Lahmer, Moritz Middelhoff, Johanna Erber, Jochen Schneider, Juliane Kager, Marina Frolova, Julia Horstmann, Lisa Fricke, Katja Steiger, Moritz Jesinghaus, Klaus-Peter Janssen, Ulrike Protzer, Klaus Neuhaus, Roland M. Schmid, Dirk Haller, Michael Quante
    bioRxiv 2021.10.08.463613; doi: https://doi.org/10.1101/2021.10.08.463613

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