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Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19
  1. Tao Zuo1,2,3,
  2. Qin Liu1,2,3,
  3. Fen Zhang1,2,3,
  4. Grace Chung-Yan Lui3,4,
  5. Eugene YK Tso5,
  6. Yun Kit Yeoh1,6,
  7. Zigui Chen1,6,
  8. Siaw Shi Boon6,
  9. Francis KL Chan1,3,
  10. Paul KS Chan1,6,
  11. Siew C Ng1,2,3
  1. 1 Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
  2. 2 State Key Laboratory for digestive disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong, China
  3. 3 Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
  4. 4 Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, China
  5. 5 Department of Medicine and Geriatrics, United Christian Hospital, Hong Kong, Hong Kong
  6. 6 Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong, 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

Objective Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19.

Design We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity.

Results Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3’ vs 5’ end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3’ vs 5’ end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA.

Conclusion This pilot study provides evidence for active and prolonged ‘quiescent’ GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.

  • gut inflammation
  • infectious disease
  • diagnostic virology
http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • TZ, QL and FZ contributed equally.

  • Contributors TZ, QL and FZ performed the experiments, data analyses and drafted the manuscript. YKY, SSB, ZC, FKLC and PC revised the manuscript and provided critical comments. GC-YL and ET recruited patients and clinical data. TZ formulated the concept and hypothesis. SCN designed and supervised the study. TZ, QL and FZ contributed equally to this work.

  • Funding This work was supported by The D. H. Chen Foundation and the Health and Medical Research Fund, Hong Kong.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committees (Reference number: 2020.076). This study was conducted in accordance with the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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