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COVID-19
Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome
  1. Qin Liu1,2,3,4,
  2. Joyce Wing Yan Mak1,2,3,
  3. Qi Su1,2,3,4,
  4. Yun Kit Yeoh1,4,5,
  5. Grace Chung-Yan Lui2,6,
  6. Susanna So Shan Ng2,
  7. Fen Zhang1,2,3,4,
  8. Amy Y L Li1,2,3,
  9. Wenqi Lu1,2,3,4,
  10. David Shu-Cheong Hui6,
  11. Paul KS Chan1,5,
  12. Francis K L Chan1,2,3,4,
  13. Siew C Ng1,2,3,4
  1. 1Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
  2. 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
  3. 3State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
  4. 4Microbiota I-Center (MagIC), Hong Kong, Hong Kong SAR, China
  5. 5Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
  6. 6Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
  1. Correspondence to Professor Siew C Ng, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong; siewchienng{at}cuhk.edu.hk

Abstract

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.

  • COVID-19
  • 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.

This article is made freely available for personal use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/gutjnl-2021-325989

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    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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    Footnotes

    • Twitter @wingyanjoyce

    • 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.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.