We appreciate the interest in probiotics to assist with the management of COVID-19 in Joyce Mak and colleagues' recent Correspondence1 in The Lancet Gastroenterology & Hepatology, but we would like to propose a more balanced and optimistic view on this topic. Further to our recent review,2 we feel that physicians now appreciate that although COVID-19 is mainly a respiratory disease, the gut can act as a reservoir for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).3 Citing meta-analyses of randomised trials that investigate the effect of probiotics on preventing respiratory tract infections, Mak and colleagues conclude that probiotics have a “modest efficacy”.1 The odds ratio in the cited Cochrane meta-analysis is 0·53 (95% CI 0·37–0·76).4 We believe that the efficacy of a treatment that leads to twice as great a reduction in the number of cases is far from modest. The potential for probiotics to reduce the risk and severity of viral respiratory tract infections is supported by clinical and experimental studies on influenza, rhinovirus, and respiratory syncytial virus.2 Although none of these effects have been tested with SARS-CoV-2, some probiotic stains do have antiviral activity against other coronaviruses.2 Given the importance of strain-to-strain differences, the selection of probiotics for testing needs to made on the basis of documented attributes.
Mak and colleagues mention that the rationale for using probiotics in COVID-19 is based on indirect evidence.1 This assertion is true for all interventions in the context of this novel disease. Ideally, preventive and therapeutic interventions should be tested in randomised controlled trials before implementation in clinical practice. In a pandemic affecting millions of people, disregarding practices that are not supported by solid evidence against this specific pathogen is not realistic. Clinicians have adopted a more pragmatic approach, and issued recommendations based on evidence from other viral infections, sepsis, and general intensive care management.5 Currently, there is no evidence from randomised controlled trials that any medication can prevent or improve the outcomes of COVID-19, and there are hundreds of ongoing trials of antivirals, immune-modulating agents, convalescent plasma, and steroids. On the basis of limited evidence showing that Bacillus Calmette-Guérin (BCG) vaccination provides heterologous protection against respiratory tract infections, randomised trials have been launched to assess whether BCG vaccination can reduce the incidence and severity of COVID-19.6 We propose that well documented probiotic strains deserve the same level of interest, and call for trials with probiotics to reduce the risk and help treat COVID-19.
Acknowledgments
EG is supported by the Leenaards Foundation. GRG reports grants from GlaxoSmithKline and Pukka Herbs, and personal fees from Clasado and Pepsico, outside the submitted work. GR reports personal fees from Seed, Danone Canada, KGK Science, and Acerus Pharma, and grants from Kimberly Clark, outside the submitted work. GR also has a patent issued on a probiotic strain to bind to heavy metals. GRG and GR are members of the Board of International Scientific Association for Probiotics and Prebiotics, a non-profit, non-lobbying group of researchers. DB and VDA declare no competing interests.
References
- 1.Mak JWY, Chan FKL, Ng SC. Probiotics and COVID-19: one size does not fit all. Lancet Gastroenterol Hepatol. 2020;5:644–645. doi: 10.1016/S2468-1253(20)30122-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Baud D, Dimopoulou Agri V, Gibson GR, Reid G, Gionnoni E. Using probiotics to flatten the curve of coronavirus disease COVID-2019 pandemic. Front Pub Health. 2020 doi: 10.3389/fpubh.2020.00186. published online May 8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Ng SC, Tilg H. COVID-19 and the gastrointestinal tract: more than meets the eye. Gut. 2020;69:973–974. doi: 10.1136/gutjnl-2020-321195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015;2 doi: 10.1002/14651858.CD006895.pub3. [DOI] [PubMed] [Google Scholar]
- 5.Alhazzani W, Møller MH, Arabi YM. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19) Intensive Care Med. 2020;46:854–887. doi: 10.1007/s00134-020-06022-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Curtis N, Sparrow A, Ghebreyesus TA, Netea MG. Considering BCG vaccination to reduce the impact of COVID-19. Lancet. 2020;395:1545–1546. doi: 10.1016/S0140-6736(20)31025-4. [DOI] [PMC free article] [PubMed] [Google Scholar]