Abstract Background and Aims Alteration in humans' gut microbiota was reported in patients infected with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). The gut and upper respiratory tract (URT) microbiota harbor a dynamic and complex population of microorganisms and have strong interaction with host immune system homeostasis. However, our knowledge about microbiota and its association with SARS‐CoV‐2 is still limited. We aimed to systematically review the effects of gut microbiota on the SARS‐CoV‐2 infection and its severity and the impact that SARS‐CoV‐2 could have on the gut microbiota. Methods We searched the keywords in the online databases of Web of Science, Scopus, PubMed, and Cochrane on December 31, 2021. After duplicate removal, we performed the screening process in two stages; title/abstract and then full‐text screening. The data of the eligible studies were extracted into a pre‐designed word table. This study adhered to the PRISMA checklist and Newcastle−Ottawa Scale Bias Assessment tool. Results Sixty‐three publications were included in this review. Our study shows that among COVID‐19 patients, particularly moderate to severe cases, the gut and lung microbiota was different compared to healthy individuals. In addition, the severity, and viral load of COVID‐19 disease would probably also be influenced by the gut, and lung microbiota's composition. Conclusion Our study concludes that there was a significant difference in the composition of the URT, and gut microbiota in COVID‐19 patients compared to the general healthy individuals, with an increase in opportunistic pathogens. Further, research is needed to investigate the probable bidirectional association of COVID‐19 and human microbiome.
