Wischmeyer PE, Tang H, Ren Y, Bohannon L, Jiang D, Bergens M, Ramirez ZE, Andermann TM, Messina JA, Sung JA, Jensen D, Jung SH, Artica A, Britt A, Bush A, Johnson E, Lew MV, Winthrop H, Pamanes C, Racioppi A, Zhao AT, Wan Z, Surana NK, and Sung AD
Background & Aims: 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 continue to be needed. Emerging evidence suggests susceptibility to respiratory tract infections in healthy subjects can be reduced by probiotic interventions; thus, probiotics may be a low-risk, low-cost, and easily implementable modality to reduce risk of COVID-19., Methods: In this initial study, we conducted a randomized, double-blind, placebo-controlled trial across the United States testing probiotic Lacticaseibacillus 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., Results: 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)., Conclusions: 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, but not overall incidence. This initial work may inform future COVID-19 prevention studies worldwide, particularly in developing nations where Lacticaseibacillus probiotics have previously been utilized to reduce other non-COVID infectious-morbidity., Trial Registration: ClinicalTrials.gov, NCT04399252, Date: 22/05/2020. https://clinicaltrials.gov/ct2/show/NCT04399252., Competing Interests: Conflict of interest P.E.W. has received unrestricted gift funding from DSM/iHealth and has an investigator-initiated research grant from Abbott Inc. related to work focused on microbiome and probiotic research. P.E.W. has presented CME lectures for DSM on probiotic research. All other authors declare no competing interests. A.D.S has grants from Merck Sharpe & Dohme, consulting for Targazyme, and receipt of supplies from Clasado., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)