COVID-19 and gut immunomodulation.

The disease coronavirus disease 2019 (COVID-19) is a severe respiratory illness that has emerged as a devastating health problem worldwide. The disease outcome is heterogeneous, and severity is likely dependent on the immunity of infected individuals and comorbidities. Although symptoms of the disease are primarily associated with respiratory problems, additional infection or failure of other vital organs are being reported. Emerging reports suggest a quite common co-existence of gastrointestinal (GI) tract symptoms in addition to respiratory symptoms in many COVID-19 patients, and some patients show just the GI symptoms. The possible cause of the GI symptoms could be due to direct infection of the epithelial cells of the gut, which is supported by the fact that (1) The intestinal epithelium expresses a high level of angiotensin-converting enzyme-2 and transmembrane protease serine 2 protein that are required for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the cells; (2) About half of the severe COVID-19 patients show viral RNA in their feces and various parts of the GI tract; and (3) SARS-CoV-2 can directly infect gut epithelial cells in vitro (gut epithelial cells and organoids) and in vivo (rhesus monkey). The GI tract seems to be a site of active innate and adaptive immune responses to SARS-CoV-2 as clinically, stool samples of COVID-19 patients possess proinflammatory cytokines (interleukin 8), calprotectin (neutrophils activity), and immunoglobulin A antibodies. In addition to direct immune activation by the virus, impairment of GI epithelium integrity can evoke immune response under the influence of systemic cytokines, hypoxia, and changes in gut microbiota (dysbiosis) due to infection of the respiratory system, which is confirmed by the observation that not all of the GI symptomatic patients are viral RNA positive. This review comprehensively summarizes the possible GI immunomodulation by SARS-CoV-2 that could lead to GI symptoms, their association with disease severity, and potential therapeutic interventions.