In recent times, the key role of the human microbiota in the body's response to infectious diseases has been increasingly demonstrated. The human microbiota is the set of symbiotic microorganisms which coexist with the human organism without harming it. However, diseases related to the microbiota occur and are being studied, and numerous publications suggest that altered microbiota composition is implicated in psychiatric diseases, chronic inflammatory diseases, and some viral infections. On the other hand, the role of the human microbiota in the host immune response to viral infections is not entirely clear. Metabolites or components produced by the microbiota are the main mediators of microbiota-host interactions that influence host immunity. It has been shown that in patients with COVID-19 and post-acute COVID-19 syndrome (PACS), the microbiota is significantly altered. In this brief review, we examine the associations between the role of the microbiota in response to COVID-19 infection in terms of molecular biology and clinical relevance. We finally discuss the mechanisms by which metabolites produced by the microbiota modulate host immune responses to SARS-CoV-2 infection.