Randomized placebo-controlled trial of oral tannin supplementation on COVID-19 symptoms, gut dysbiosis and cytokine response

[Display omitted] •Gut dysbiosis correlated with systemic inflammation in COVID-19 patients.•Dysbiosis in COVID-19 patients was antibiotic-independent.•Oral tannins reduced systemic inflammation but was not clinically efficacious.•Tannins inhibited MIP-1α, which negatively correlated with Bifidobacterium abundance. The clinical study aim was to investigate whether a tannin-based dietary supplementation could improve the efficacy of standard-of-care treatment of hospitalized COVID-19 patients by restoring gut microbiota function. Adverse events and immunomodulation post-tannin supplementation were also investigated. A total of 124 patients receiving standard-of-care treatment were randomized to oral tannin-based supplement or placebo for a total of 14 days. Longitudinal blood and stool samples were collected for cytokine and 16S rDNA microbiome profiling, and results were compared with 53 healthy controls. Although oral tannin supplementation did not result in clinical improvement or significant gut microbiome shifts after 14-days, a reduction in the inflammatory state was evident and significantly correlated with microbiota modulation. Among cytokines measured, MIP-1α was significantly decreased with tannin treatment (p = 0.03) where it correlated positively with IL-1β and TNF- α, and negatively with stool Bifidobacterium abundance.