Letter: role of probiotics in the COVID-19 pandemic-authors' reply.

EDITORS,

We read with great interest the review of our article by Dr Aguila and colleagues. We are grateful for their comments. Probiotics have been a hot and controversial topic in recent years. We agree that probiotics may be potentially helpful in the treatment of patients with severe COVID‐19, but there is a lack of evidence to demonstrate the effect of probiotics directly inhibiting SARS‐CoV‐2 infection.

In the early days of the outbreak, antibiotics were commonly used empirically to prevent secondary bacterial infection. A review of 18 articles showed that although only 8% (62/806) of COVID‐19 patients experienced bacterial/fungal co‐infection, 72% (1450/2010) received antimicrobial therapy. Besides co‐infection, patients possibly suffered from the loss of helpful symbionts and from gut dysbiosis since most were severely or critically ill. Zuo et al reported differences in faecal microbiomes in 15 patients with moderate or severe COVID‐19, supporting the use of probiotics as a potential treatment for COVID‐19. However, the presence of altered gut microbiota in mild or asymptomatic patients needs to be verified.

Many studies have demonstrated the pathogenic links between microbiota and the gut‐lung axis, which is a dynamic immune balance between these two mucosal sites. A respiratory pathogen may cause gut and lung dysbiosis as well as altered leucocyte level and activation disorders. Reintroduction of probiotics promotes the release of short chain fatty acids from microbiota or cytokines and chemokines from the lungs or gut of the host, thereby facilitating the recovery of a healthy microbiota composition as well as leucocyte homoeostasis and activation. This helps prevent infection and immunopathogenesis. Therefore, probiotics may be more effective in treating patients with severe COVID‐19 with a high level of inflammatory factors or those with a high risk of co‐infection due to mechanical ventilation.

As suggested in the guideline drafted by China's National Health Commission, patients with a long hospital stay, more complications, poor immunity status or a rapidly progressive disease course may benefit more from probiotics. Probiotics were capable of reducing infections, systemic inflammatory response syndrome, sepsis, days under mechanical ventilation, and mortality in critical illness. However, there is little evidence to support a direct effect of preventing SARS‐CoV‐2 infection. Although Lactobacillus and Bifidobacterium decreased in some patients with COVID‐19, the choice and effect of probiotics require further study. We do not recommend probiotics for routine treatment of COVID‐19 as most patients were mild and asymptomatic and dysbiosis of the intestinal flora was self‐limiting in most cases. We do believe that it would be worthwhile to evaluate probiotics in critically ill COVID‐19 patients.