Safety and efficacy of probiotic supplements as adjunctive therapies in patients with COVID-19: A systematic review and meta-analysis

Background and aims: Oral probiotic supplementation may be a beneficial adjunctive therapy for patients with symptomatic COVID-19. However, its safety and efficacy are unclear. We aimed to investigate how probiotic supplementation impacts COVID-19 symptom trajectory and patient outcomes by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: RCTs randomizing patients with COVID-19 to probiotics were searched in PubMed Central, Embase, CINAHL, and Cochrane Library from inception to July 31, 2022. We performed a random-effects pairwise meta-analysis for all outcomes using the restricted maximum likelihood (REML) estimator. We used the GRADE approach to assess the certainty of the evidence. Results: A total of 1027 participants from eight RCT studies were included in the meta-analysis. Probiotic supplements probably reduce the incidence of diarrhea (RR 0.61 [0.43 to 0.87]; moderate certainty) and probably reduce cough or dyspnea compared to placebo/standard care (RR 0.37 [0.19 to 0.73]; moderate certainty). Probiotic supplements may improve composite endpoint measured by clinical escalation or mortality compared to placebo (RR 0.41 [0.18 to 0.93]; low certainty evidence); however, they may not significantly reduce the need for clinical escalation (RR 0.57 [0.31 to 1.07]; low certainty evidence) or mortality (RR 0.50 [0.20 to 1.29]; low certainty evidence). In addition, the probiotic supplement is associated with reduced adverse events (RR 0.62 [0.46 to 0.83]; moderate certainty). Conclusion: Early probiotic supplement is a safe and effective adjunctive therapy that reduces the risk of symptoms and health care burden related to COVID-19 across all severity types.