Efficacy of probiotic treatment as post-exposure prophylaxis for COVID-19: A double-blind, Placebo-Controlled Randomized trial.

Paul E Wischmeyer, Helen Tang, Yi Ren, Lauren Bohannon, Danting Jiang, Matthew Bergens, Zeni E Ramirez, Tessa M Andermann, Julia A Messina, Julia A Sung, David Jensen, Sin-Ho Jung, Alexandra Artica, Anne Britt, Amy Bush, Ernaya Johnson, Meagan V Lew, Hilary Winthrop, Claudia Pamanes, Alessandro Racioppi, Aaron T Zhao, Zihan Wan, Neeraj K Surana, Anthony D Sung

Journal: Clinical nutrition (Edinburgh, Scotland) 2023;43(1):259-267

PMID: 38103462

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Plain Language Summary

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus infection, continues to pose a unique and novel challenge to global health. Ongoing research is showing a potentially significant role of the microbiome and dysbiosis in COVID-19 disease severity and development of Long-Covid. The aim of this study was to investigate the efficacy of the probiotic Lacticaseibacillus rhamnosus GG (LGG) as post-exposure prophylaxis against COVID-19. This study was a randomised, double-blind, placebo-controlled trial. Participants were randomised to receive LGG or placebo in a 1:1 ratio. Results showed that the participants randomised to LGG had fewer symptoms and prolonged time to development of COVID-19 compared to those receiving placebo. Additionally, probiotic supplementation also reduced symptomatic disease, and changed the gut microbiome structure. Authors conclude that their findings lend credence to the notion that symbiotic microbes may be valuable partners in the fight against COVID-19 and potentially other future pandemic diseases.

Abstract

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.

Address: Duke University School of Medicine, Department of Anesthesiology, Durham, NC, USA. Electronic address: [email protected].; Duke University School of Medicine, Durham, NC, USA.; Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, NC, USA.; Division of Infectious Diseases, Department of Pediatrics, Duke University, Durham, NC, USA; Program in Computational Biology and Bioinformatics, Duke University, Durham, NC, USA.; Division of Infectious Diseases, Department of Pediatrics, Duke University, Durham, NC, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA.; Duke University Trinity College of Arts & Sciences, Durham, NC, USA.

DOI: 10.1016/j.clnu.2023.11.043