Objective: What we learned from two years of pandemic is that COVID-19 disease can appear with a wide spectrum of clinical symptoms ranging from the “typical” respiratory symptoms, such as fever, cough, interstitial pneumonia, respiratory distress/ARDS, to “less-typical” ones including abdominal pain, diarrhea, nausea/vomiting, anorexia. This turns the spotlight on the role of microbiota gut and gut barrier in preventing or predisposing to Sars-Cov-2 infection, its complications and outcomes. Although many studies have been conducted, many questions remain still opened today.

Material and methods: We performed literature research on PubMed®, Up-To-Date®, Web of Science®, and collected metanalysis, systematic reviews, clinical trials, case control studies, retrospective and prospective articles published in the last two years.

Results: Our review article suggests that changes in the gut microbiota composition with an altered gut permeability (“leaky gut”) may lead to a systemic involvement with more severe COVID-19 manifestations, need of intensive care and may be associated with worse outcomes.

Conclusions: The use of strategies and treatments (as probiotics), to prevent and keep the gut microbiota balanced in the Emergency Department may improve both the symptoms of patients, multiorgan complications and the length of hospitalization of COVID-19 patients.