Probiotics and COVID-19: one size does not fit all.

As of April 20, 2020, coronavirus disease 2019 (COVID-19) has affected more than 2 million people globally. In February, 2020, China's National Health Commission and National Administration of Traditional Chinese Medicine suggested the use of probiotics in patients with severe COVID-19. We reviewed the evidence for the role of probiotics in COVID-19-related illnesses (appendix).

In China, 58–71% of patients with COVID-19 were given antibiotics, and diarrhoea occurred in 2–36% of patients.2, 3, 4 When antibiotics are used, reinforcement of colonic flora using probiotics has been proposed to reduce susceptibility to subsequent infections. Although a 2012 meta-analysis showed that probiotics have modest efficacy in reducing antibiotic-associated diarrhoea, the largest randomised, placebo-controlled trial (involving 2941 participants) showed that a 21-day treatment of combined Lactobacilli and Bifidobacteria did not reduce antibiotic-associated diarrhoea. Even if probiotics are useful, they are unlikely to have a direct effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; most patients with COVID-19 present with respiratory symptoms. However, gut–lung crosstalk has been proposed in the pathogenesis of certain respiratory conditions. Two meta-analyses reported modest efficacy of probiotics in reducing the incidence and duration of respiratory tract infections of viral origin.7, 8 During the COVID-19 pandemic, 2–47% of infected patients required invasive mechanical ventilation.3, 4 Two randomised controlled trials showed that critically ill patients on mechanical ventilation who were given probiotics (Lactobacillus rhamnosus GG, live Bacillus subtilis, and Enterococcus faecalis) developed substantially less ventilator-associated pneumonia compared with placebo.9, 10 However, the efficacy of probiotics in reduction of intensive care unit mortality and inpatient mortality is uncertain.

Scarce data are available on the effect of COVID-19 on intestinal microbiota. A small case series from China revealed that some patients with COVID-19 showed microbial dysbiosis with decreased Lactobacillus and Bifidobacterium. However, animal studies (as yet, not peer-reviewed) showed that Lactobacillus acidophilus and Bacillus clausii did not reduce coronavirus receptor expression in the murine small intestine compared with control and post-Salmonella infection models. Not all probiotics are likely to be the same. Lactobacilli and Bifidobacteria are only two types of non-pathogenic bacteria and we must consider whether they can really tip the balance of a diverse gut ecosystem in combating COVID-19. To date, the rationale for using probiotics in COVID-19 is derived from indirect evidence. Blind use of conventional probiotics for COVID-19 is not recommended until we have further understanding of the pathogenesis of SARS-CoV-2 and its effect on gut microbiota. It is likely that a novel and more targeted approach to modulation of gut microbiota as one of the therapeutic approaches of COVID-19 and its comorbidities will be necessary.