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The SARS-CoV-2 infection disrupts the normal mix of gut bacteria, allowing harmful bacteria to enter the bloodstream and raising the risk for potentially life-threatening secondary bloodstream infections (BSIs), new research suggests.
“Collectively, these results reveal an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs,” the study team reports in Nature Communications.
“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” microbiologist and cosenior author Ken Cadwell, PhD, New York University Grossman School of Medicine, New York City, adds in a news release. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”
In a mouse model, the researchers first demonstrated that the SARS-CoV-2 infection alone induces gut microbiome dysbiosis and gut epithelial cell alterations, which correlate with markers of gut barrier permeability.
Next, they analyzed the bacterial composition of stool samples from 96 adults hospitalized with COVID-19 in 2020 in New York City and New Haven, Connecticut.
In line with their observations in mice, they found that the SARS-CoV-2 infection is associated with “severe microbiome injury,” characterized by the loss of gut microbiome diversity.
They also observed an increase in populations of several microbes known to include antibiotic-resistant species. An analysis of stool samples paired with blood cultures found that antibiotic-resistant bacteria in the gut migrated to the bloodstream in 20% of patients.
This migration could be due to a combination of the immune-compromising effects of the viral infection and the antibiotic-driven depletion of commensal gut microbes, the researchers say.
However, COVID-19 patients are also uniquely exposed to other potential factors predisposing them to bacteremia, including immunosuppressive drugs, long hospital stays, and catheters, the investigators note. The study is limited in its ability to investigate the individual effects of these factors, they add.
“Our findings support a scenario in which gut-to-blood translocation of microorganisms following microbiome dysbiosis leads to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics,” the researchers write.
Investigating the underlying mechanism behind their observations could help inform “the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics,” they add.
Funding for the study was provided by the National Institutes of Health, and by the Yale School of Public Health, the Beatrice Kleinberg Neuwirth Fund, the Howard Hughes Medical Institute, the Crohn’s and Colitis Foundation, the Kenneth Rainin Foundation, the Judith and Stewart Colton Center of Autoimmunity, the Jan Vilcek/David Goldfarb Fellowship Endowment Funds, The G. Harold and Leila Y. Mathers Charitable Foundation, the Yale COVID-19 Research Resource Fund, and the Bristol Myers Squibb Foundation. Cadwell has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie; consulted for or received an honoraria from PureTech Health, Genentech, and AbbVie; and is named as an inventor on US patent 10,722,600 and provisional patents 62/935,035 and 63/157,225.
Nat Commun. Published online November 1, 2022. Full text