Abstract
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 in a mouse model that SARS-CoV-2 infection can induce gut microbiome dysbiosis, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Comparison with stool samples collected from 96 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 indicates that bacteria may 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.
Footnotes
We have made substantial changes including: (1) addition of crucial data on antibiotics administered to human patients in the study, (2) improved microbiota analysis with better resolution of the microbiota-BSI analyses, addition of ASV level analyses in support of our major findings, and increased resolution with shotgun sequencing of select BSI-associated samples, (3) addition of several mouse experiments to provide better mechanistic insights including new findings of epithelial cell changes associated with microbiota dysbiosis, and (4) improved reporting of the clinical cohort and samples.
