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Research
Siew Ng
Chinese University of Hong Kong
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6850-4454
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 faecal 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 virome) that play a role in regulating host immunity and 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 study subjects had faecal specimens sampled at inclusion. Blood specimens were sampled for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serially faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome respectively. 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 faecal samples, compared to non-COVID-19 subjects. Such gut virome dysbiosis persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured 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. Human faecal baseline abundance of 10 virus species (1 RNA virus, Pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease severity of COVID-19. These viruses were also inversely associated 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 viromes were perturbed in COVID-19, which prolonged even after disease resolution. 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 partly explains that older subjects are prone to severe and unfavorable COVID-19 outcomes. Our data altogether highlight the significance of human gut virome in COVID-19 disease course and potentially therapeutics.
Keywords
RNA and DNA, Coronavirus Disease 2019, infection, chlorotic spot virus
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Peer Review Timeline
CURRENT STATUS: Published
View the published article at Microbiome.
No community comments so far
Editorial decision: Accept
On 10 Jan, 2021
Editor assigned
On 07 Dec, 2020
Submission checks complete
On 07 Dec, 2020
Editor invited
On 07 Dec, 2020
Version 1
Posted 04 Sep, 2020
No comments provided
Review #3 received
Received 01 Nov, 2020
Editorial decision: Minor revision
On 01 Nov, 2020
Review #2 received
Received 20 Oct, 2020
Review #1 received
Received 18 Oct, 2020
Reviewer #3 agreed
On 12 Oct, 2020
Reviewer #2 agreed
On 23 Sep, 2020
Reviewer #1 agreed
On 22 Sep, 2020
Reviewers invited
Invitations sent on 14 Sep, 2020
Editor invited
On 02 Sep, 2020
Editor assigned
On 30 Aug, 2020
Submission checks complete
On 29 Aug, 2020
First submitted
On 28 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at Microbiome.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Siew Ng
Chinese University of Hong Kong
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6850-4454
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Microbiome.
No community comments so far
Editorial decision: Accept
On 10 Jan, 2021
Editor assigned
On 07 Dec, 2020
Submission checks complete
On 07 Dec, 2020
Editor invited
On 07 Dec, 2020
Version 1
Posted 04 Sep, 2020
No comments provided
Review #3 received
Received 01 Nov, 2020
Editorial decision: Minor revision
On 01 Nov, 2020
Review #2 received
Received 20 Oct, 2020
Review #1 received
Received 18 Oct, 2020
Reviewer #3 agreed
On 12 Oct, 2020
Reviewer #2 agreed
On 23 Sep, 2020
Reviewer #1 agreed
On 22 Sep, 2020
Reviewers invited
Invitations sent on 14 Sep, 2020
Editor invited
On 02 Sep, 2020
Editor assigned
On 30 Aug, 2020
Submission checks complete
On 29 Aug, 2020
First submitted
On 28 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Microbiome.
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 faecal 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 virome) that play a role in regulating host immunity and 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 study subjects had faecal specimens sampled at inclusion. Blood specimens were sampled for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serially faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome respectively. 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 faecal samples, compared to non-COVID-19 subjects. Such gut virome dysbiosis persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured 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. Human faecal baseline abundance of 10 virus species (1 RNA virus, Pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease severity of COVID-19. These viruses were also inversely associated 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 viromes were perturbed in COVID-19, which prolonged even after disease resolution. 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 partly explains that older subjects are prone to severe and unfavorable COVID-19 outcomes. Our data altogether highlight the significance of human gut virome in COVID-19 disease course and potentially therapeutics.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
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