Gastrointestinal Symptoms and Immune Response in COVID-19 - Review of a Cat and Mouse Game Theory.

Gastrointestinal (GI) symptoms are not uncommon in covid-19 infection. The varied symptomatology and severity of GI symptoms are related to the difference in host viral interaction. We have reviewed the GI manifestations of these patients and noted that three subgroups exist. Group with self-limited GI disease, group with predominant GI manifestations and group with severe GI disease. A review of the immune response in the different groups with GI manifestations has been done and illustrated by a cat and mouse game theory. In self-limited GI disease there is early effective innate immunity with type I interferon response and is followed by an efficient adaptive immune response causing viral clearance. In patients with predominant GI symptoms viral factors override innate immune mechanisms and cause delayed and weak innate antiviral response. Ensuing adaptive response is a “mishit” response with mucosal injury and GI symptoms. In the later part of this infection a resurgent adaptive immunity induction can occur causing persistent fecal shedding followed by viral clearance. In severe disease there is heightened dysregulation of adaptive immune response leading to cytokine storm and its severe complications like pyroptosis, endothelitis and hemophagocytic lymphohistiocytosis.