Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19.
Yun Kit Yeoh, Tao Zuo, Grace Chung-Yan Lui, Fen Zhang, Qin Liu, Amy Yl Li, Arthur Ck Chung, Chun Pan Cheung, Eugene Yk Tso, Kitty Sc Fung, Veronica Chan, Lowell Ling, Gavin Joynt, David Shu-Cheong Hui, Kai Ming Chow, Susanna So Shan Ng, Timothy Chun-Man Li, Rita Wy Ng, Terry Cf Yip, Grace Lai-Hung Wong, Francis Kl Chan, Chun Kwok Wong, Paul Ks Chan, Siew C Ng
Author Information
Yun Kit Yeoh: Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong. ORCID
Tao Zuo: Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong. ORCID
Grace Chung-Yan Lui: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
Fen Zhang: Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Qin Liu: Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Amy Yl Li: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
Arthur Ck Chung: Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Chun Pan Cheung: Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Eugene Yk Tso: Department of Medicine and Geriatrics, United Christian Hospital, Kwun Tong, Hong Kong.
Kitty Sc Fung: Department of Pathology, United Christian Hospital, Kwun Tong, Hong Kong.
Veronica Chan: Department of Medicine and Geriatrics, United Christian Hospital, Kwun Tong, Hong Kong.
Lowell Ling: Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.
Gavin Joynt: Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.
David Shu-Cheong Hui: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
Kai Ming Chow: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong. ORCID
Susanna So Shan Ng: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
Timothy Chun-Man Li: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
Rita Wy Ng: Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong.
Terry Cf Yip: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
Grace Lai-Hung Wong: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong. ORCID
Francis Kl Chan: Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong. ORCID
Chun Kwok Wong: Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong.
Paul Ks Chan: Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong.
Siew C Ng: Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong siewchienng@cuhk.edu.hk. ORCID
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 , 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.
