The digestive system is an environmental frontline involving digestive secretions, intestinal cell metabolism, and gut microbiome that significantly
modulate multiple functions in organisms. Understanding the ‘gut-lung axis’, where gut residential microbiota play important roles, may help in
the development of better prophylactics and intervention strategies for diseases caused by respiratory viruses, including coronavirus disease of
2019 (COVID-19). Gastrointestinal symptoms are common in COVID-19 patients and are generally indicative of disease complications. As we
have learned so far, diarrhea and gut dysbiosis during SARS-CoV-2 infection should not be ignored, as they can be used to distinguish pathways
of dysregulation of the immune system and the regulatory pathways upstream and downstream of viral primary binding receptors such as ACE2.
This review presents evidence of microbiome signatures in the gut and respiratory system that may predict the severity and long-term outcomes
of COVID-19. Understanding the factors (such as pro-inflammatory trends, modulation of metabolite availability, and impact on cell signaling and
pathogenic properties) translating the effect of microbiome composition on the severity of respiratory infections should help in the development of
new approaches for health monitoring, disease prevention, and treatment.