Background Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear.
Objective To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus.
Methods We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months.
Results At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii (all p<0.05). Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months.
Conclusion These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.
- intestinal microbiology
Data availability statement
Data are available in a public, open access repository. Raw data are deposited in a BioProject in the NCBI Sequence Read Archive: PRJNA714459.
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QL, JWYM and QS contributed equally.
Correction notice This article has been corrected since it published Online First. The affiliations have been updated.
Contributors QL and JWYM conceived and designed the study and took responsibility for the integrity of the data and preparation of manuscript. QL and QS performed microbiome analysis. QL is the guarantor for this paper. YKY critically revised the manuscript for important intellectual content of microbime. GC-YL and SSSN contributed to collection of the clinical data. AYLL contributed to analysis of clinical data. FZ and WL contributed to metagenomic sequencing. DS-CH and PC contributed to study design. SCN and FKLC contributed to the study design, direction, guidance and manuscript writing.
Funding This project was supported by a seed fund for Gut Microbiome Research provided by the Faculty of Medicine, The Chinese University of Hong Kong, and InnoHK@Health provided by Hong Kong Special Administrative Region Government, China.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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