Probiotics for preventing or treating COVID-19; a systematic review of research evidence and meta-analyses of efficacy for preventing death, severe disease, or disease progression

Background: COVID-19 variants threaten health globally. Despite improving vaccines and treatments, there is an urgent need for alternative strategies to prevent or reduce the severity of COVID-19. Potential strategies include probiotics, which are safe, inexpensive, globally available and have been studied previously in relation to respiratory infections. Methods: We performed a systematic review and meta-analyses of experimental, trial or observational research evidence evaluating probiotics compared with control groups for preventing or treating COVID-19. We searched PubMed, ProQuest, Google Scholar and Web of Science bibliographic databases for studies published until December 6, 2021. We then performed meta-analyses for outcomes reported consistently across studies. Outcomes reported inconsistently or not amenable to meta-analysis were compared descriptively. Results: We identified six eligible studies, which were all published in 2020 and 2021: one randomized controlled trial and five retrospective cohort studies. The only randomized controlled trial reported that groups that ingested probiotics compared with control groups that did not ingest probiotics did not differ significantly with respect to death, severe disease requiring admission to an intensive care unit or disease progression (all p>0.5). The five retrospective cohort studies reported various apparently beneficial and harmful COVID-19 outcome associations with probiotic ingestion. Meta-analyses revealed no significant associations between probiotic use and death, severe disease, or disease progression caused by COVID-19. Descriptive data revealed that probiotic ingestion was associated with a trend towards worsened duration of hospital stay, improvements in measures of respiratory condition and worsened disease duration. The evidence for these contradictory associations was weak because all studies were prone to bias and none were considered to be of high quality. Conclusions: Current evidence does not suggest that probiotics affect COVID-19 severity or mortality. However, additional higher quality studies need to be conducted to definitively determine if probiotics would be a useful adjunctive treatment for COVID-19.