Objective Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.
Methods In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.
Results Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.
Conclusion Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
- colonic microflora
- colonic bacteria
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PKC and SCN are joint senior authors.
Twitter @Tao_Zuo_, @Siew_C_Ng
YKY, TZ and CKW contributed equally.
Contributors SCN, GC-YL, ET, KSCF, VC, LL recruited study subjects. AYLL, RWYN, TCFY, GL-HW procured and collated patients’ clinical data. PC organised sample inventory and processing. TZ, QL, FZ, AC, CPC performed laboratory work including extracting DNA and generating sequence data. CKW performed cytokine and chemokine measurements. YKY and SCN analyzed and interpreted the data, and wrote the manuscript. GJ, DS-CH and other authors reviewed the manuscript. SCN, PC and FKLC designed and supervised the study.
Funding This study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (COVID190111), and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study has been approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (reference number 2020.076). Written informed consent was obtained from all participants prior to collecting stool samples.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access repository. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA650244. Raw sequence data are available in the Sequence Read Archive (SRA) under BioProject accession PRJNA650244.
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