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