COVID-19 infection is caused by a betacoronavirus, SARS-CoV-2. It is highly variable in symptoms and clinical outcomes, ranging from mild to fatal forms. Hyperactivation of the immune system is potentially the factor precipitating the severe forms and mortalities of this infection. Both adaptive and innate immune responses to COVID-19 infection determine the natural history and progression of COVID-19. Microbiome (MB) often refers to the microbial taxa associated with man. Microbiome has many hostrelated functions. The gut has the largest population of microbes, and thus may have a vast impact on host health. Microbiome is involved in evolution of innate and adaptive immune system in humans, among other functions. Perturbations in composition of MB are referred to as dysbiosis. Dysbiosis can coincide with COVID-19 itself and be also drug-induced. Antibiotics commonly prescribed to COVID-19 patients often exert deleterious effects on composition of gut MB. In light of host-related microbiome functions, this possibly has consequences impacting severity and outcome of COVID-19. Gut microbiome integrity can be a crucial factor in COVID-19 patients, thus antibiotic use, in light of its impact on gut flora, may adversely affect disease outcome; however, the extent of these aspects is still unclear. A rational antibiotic use strategy should be an integral part in all COVID-19 therapeutic plans.