Efficacy of Probiotic Treatment as Post-Exposure Prophylaxis for COVID-19: A Double-Blind, Placebo Controlled Randomized Trial

The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, additional strategies to mitigate the spread/severity of COVID-19 are urgently needed. Emerging evidence suggests susceptibility to respiratory tract infections in healthy subjects can be reduced by probiotic interventions; therefore, probiotics may be a low-risk, easily implementable modality to reduce risk of COVID-19, particularly in areas with low vaccine availability/uptake. In this study, we conducted a randomized, double-blind, placebo-controlled trial across the United States testing probiotic Lactobacillus rhamnosus GG (LGG) as postexposure prophylaxis for COVID-19 in 182 participants who had household exposure to someone with confirmed COVID-19 diagnosed within ≤ 7 days. Participants were randomized to receive oral LGG or placebo for 28 days. The primary outcome was development of illness symptoms within 28 days of COVID-19 exposure. Stool was collected to evaluate microbiome changes. Intention-to-treat analysis showed LGG treatment led to a lower likelihood of developing illness symptoms versus placebo (26.4% vs. 42.9%, p = 0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank, p = 0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis did not significantly differ between LGG and placebo groups (8.8% vs. 15.4%, p = 0.17). This data suggests LGG is associated with prolonged time to COVID-19 infection, reduced incidence of illness symptoms, and gut microbiome changes when used as prophylaxis ≤ 7 days post-COVID-19 exposure. This initial work may inform future COVID-19 prevention studies worldwide, particularly in underdeveloped nations where Lactobacillus probiotics have previously been utilized to reduce non-COVID infectious-morbidity. Trial registration ClinicalTrials.gov, NCT04399252, Date: 22/05/2020 https://clinicaltrials.gov/ct2/show/NCT04399252