RT Journal Article SR Electronic T1 Gut Bacterial Dysbiosis and Instability is Associated with the Onset of Complications and Mortality in COVID-19 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.08.463613 DO 10.1101/2021.10.08.463613 A1 David Schult A1 Sandra Reitmeier A1 Plamena Koyumdzhieva A1 Tobias Lahmer A1 Moritz Middelhoff A1 Johanna Erber A1 Jochen Schneider A1 Juliane Kager A1 Marina Frolova A1 Julia Horstmann A1 Lisa Fricke A1 Katja Steiger A1 Moritz Jesinghaus A1 Klaus-Peter Janssen A1 Ulrike Protzer A1 Klaus Neuhaus A1 Roland M. Schmid A1 Dirk Haller A1 Michael Quante YR 2021 UL http://biorxiv.org/content/early/2021/10/09/2021.10.08.463613.abstract AB 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 StatementThe authors have declared no competing interest.AB T1Antibiotic therapy at the time of the first stool samplingACAsymptomatic controlsAKIAcute kidney injuryAPAlkaline phosphatase [U/l]ARDSAcute respiratory distress syndromeAsympt.AsymptomaticCOVID-19Corona virus disease 2019CRPC-reactive protein [mg/dl]FiO2Fraction of inspired oxygen (%)GGTGamma-Glutamyltransferase [U/l]GIGastrointestinalHbHemoglobin [g/dl]i.v.intravenousIBDInflammatory bowel diseaseICUIntensive care unitICU all TIntensive care stay regarding all time points of stool samplingICU T1Intensive care stay at the time of the first stool samplingNNumber of patientsnNumber of samplesNAnot availablePAPressure assistedPCPressure controlledPCTProcalcitonin [ng/ml]PEPulmonary embolismRel.RelativeS.p.Status postSARS-CoV-2Severe acute respiratory syndrome coronavirus 2SCSymptomatic pneumonia controlsSig.SignificantSympt.SymptomaticT1First sampling time pointT2DType 2 diabetes mellitusTrp THigh-sensitive troponin T [ng/ml]TSTracheostomyVTEVenous thromboembolismWBCWhite blood cells counts [G/l]zOTUZero-radiation operational-taxonomic units