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Gut Microbiome and COVID-19 Severity: New Evidence for Link

— Lab study finds certain patterns associated with more serious illness

MedpageToday
A computer rendering of the gut microbiome microbes

The gut microbiome may play a role in COVID-19 severity, a lab study suggested.

Patients with depleted levels of certain species of bacteria were associated with elevated concentrations of inflammatory cytokines, and blood markers including C-reactive protein, lactate dehydrogenase, and aspartate aminotransferase, reported Siew Ng, PhD, of The Chinese University of Hong Kong, and colleagues, in Gut.

The researchers noted that patients with severe disease exhibit high blood plasma levels of inflammatory cytokines and inflammatory markers, and that there is "substantial involvement" of the gastrointestinal tract in SARS-CoV-2 infection, given "altered gut microbiota composition in SARS-CoV-2 infected subjects." They hypothesized gut microbiota would be associated with host inflammatory immune responses in COVID-19.

The authors examined blood and stool samples from 100 confirmed positive COVID-19 patients in two Hong Kong hospitals from February to March 2020, including serial stool samples in 27 of 100 patients up to 30 days after clearance of SARS-CoV-2. Eleven patients had hypertension, but fewer than five patients had any other comorbidity. In total, 41 patients provided multiple stool samples during their hospital stay and/or follow-up after discharge.

Patients had a mean age of about 36, and 53 were men. Nearly all patients had mild or moderate disease, with only 5% with severe and 3% with critical disease.

Compared with a group of adult controls without COVID-19, these patients had more Ruminococcus gnavus, Ruminococcus torques, and Bacteroides dorei species, regardless of whether or not patients received medication.

When examining samples from 87 hospitalized COVID-19 patients, researchers found a "continuum" among the mild, moderate, severe, and critical patients "indicating a stratification of gut microbiota composition associated with disease severity." Measurements of cytokines and certain enzymes from plasma were "significantly associated with microbiota composition," and in fact "increased concomitant with microbiota composition representing more severe disease states."

"These results suggest that gut microbiota composition is associated with the magnitude of immune response to COVID-19 and subsequent tissue damage and thus could play a role in regulating disease severity," they wrote.

They suggested this role of gut microorganisms could contribute to a "microbiome-based risk profile" to identify those at risk of inflammatory symptoms, such as multi-system inflammatory syndrome in children (MIS-C), and severe disease.

In addition, they found because a small subset of patients showed gut microbiota dysbiosis even 30 days after clearance of SARS-CoV-2, this could be a potential explanation for why COVID-19 symptoms, such as fatigue, dyspnea, and joint pain, tend to persist even following recovery.

Limitations to the data include heterogenous patient management, which could have influenced microbial signatures. The authors noted a more controlled study was needed to confirm these findings, as it is unclear how much of gut microbiota is affected by patient management.

"The observed gut microbiota composition could simply be a response to patients' health and immune states rather than a direct involvement in disease severity, as such it may not be directly applicable to predicting disease susceptibility in non-COVID-19 subjects," they wrote.

  • author['full_name']

    Molly Walker is deputy managing editor and covers infectious diseases for 鶹ý. She is a 2020 J2 Achievement Award winner for her COVID-19 coverage.

Disclosures

The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, Hui Hoy & Chow Sin Lan Charity Fund, Pine and Crane, Mr. Hui Ming, and The D.H. Chen Foundation.

The authors disclosed no relevant relationships with industry.

Primary Source

Gut

Keoh YK, et al "Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19" Gut 2021; DOI: 10. 1136/ gutjnl- 2020- 323020.