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Temporal landscape of human gut RNA and DNA virome in SARS-CoV-2 infection and severity.
Zuo, Tao; Liu, Qin; Zhang, Fen; Yeoh, Yun Kit; Wan, Yating; Zhan, Hui; Lui, Grace C Y; Chen, Zigui; Li, Amy Y L; Cheung, Chun Pan; Chen, Nan; Lv, Wenqi; Ng, Rita W Y; Tso, Eugene Y K; Fung, Kitty S C; Chan, Veronica; Ling, Lowell; Joynt, Gavin; Hui, David S C; Chan, Francis K L; Chan, Paul K S; Ng, Siew C.
  • Zuo T; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Liu Q; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Zhang F; State Key Laboratory for Digestive disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Yeoh YK; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Wan Y; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Zhan H; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Lui GCY; State Key Laboratory for Digestive disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Chen Z; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Li AYL; Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong, China.
  • Cheung CP; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Chen N; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Lv W; State Key Laboratory for Digestive disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Ng RWY; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Tso EYK; Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong, China.
  • Fung KSC; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Chan V; Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong, China.
  • Ling L; Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Joynt G; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Hui DSC; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Chan FKL; State Key Laboratory for Digestive disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Chan PKS; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Ng SC; Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong, China.
Microbiome ; 9(1): 91, 2021 04 14.
Article in English | MEDLINE | ID: covidwho-1183579
Semantic information from SemMedBD (by NLM)
1. Virome COEXISTS_WITH COVID-19
Subject
Virome
Predicate
COEXISTS_WITH
Object
COVID-19
2. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
3. COVID-19 COEXISTS_WITH Disease
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Disease
4. COVID-19 COEXISTS_WITH Disease Progression
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Disease Progression
5. Virome PROCESS_OF Patients
Subject
Virome
Predicate
PROCESS_OF
Object
Patients
6. Virome COEXISTS_WITH COVID-19
Subject
Virome
Predicate
COEXISTS_WITH
Object
COVID-19
7. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
8. COVID-19 COEXISTS_WITH Disease
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Disease
9. COVID-19 COEXISTS_WITH Disease Progression
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Disease Progression
10. Virome PROCESS_OF Patients
Subject
Virome
Predicate
PROCESS_OF
Object
Patients
ABSTRACT

BACKGROUND:

Coronavirus disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from fecal samples, and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need.

METHODS:

We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had fecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial fecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the fecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters.

RESULTS:

Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in fecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Fecal virome in SARS-CoV-2 infection harbored more stress-, inflammation-, and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells, and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects.

CONCLUSIONS:

Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether, our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19. Video Abstract.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Gastrointestinal Microbiome / COVID-19 Type of study: Observational study Limits: Child, preschool / Humans Language: English Journal: Microbiome Year: 2021 Document Type: Article Affiliation country: S40168-021-01008-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Gastrointestinal Microbiome / COVID-19 Type of study: Observational study Limits: Child, preschool / Humans Language: English Journal: Microbiome Year: 2021 Document Type: Article Affiliation country: S40168-021-01008-x