Gut microbiome dysbiosis during COVID-19 is associated with increased risk for bacteremia and microbial translocation

The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate that the gut microbiome is directly affected by SARS-CoV-2 infection in a dose-dependent manner in a mouse model, causally linking viral infection and gut microbiome dysbiosis. Comparison with stool samples collected from 101 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients suggest that bacteria translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19. ### Competing Interest Statement KC 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 holds U.S. patent 10,722,600 and provisional patents 62/935,035 and 63/157,225. JS is cofounder of Postbiotics Plus Research LLC.