The Pathophysiology of Gastrointestinal and Hepatic Manifestations of COVID-19

Coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the sixth international public health emergency. While COVID-19 classically manifests as a respiratory illness, SARS-CoV-2 may infect multiple organ systems and cause a wide array of presentations. The gastrointestinal tract has become increasingly recognized as a site of SARS-CoV-2 infection with reports of diarrhea, nausea, and liver failure, with or without concomitant respiratory involvement. In this case series and literature review, we report three cases of SARS-CoV-2 infected patients that presented with predominantly gastrointestinal symptoms or laboratory abnormalities such as diarrhea, anorexia, and transaminitis. The receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), as well as the necessary protease to facilitate viral entry, transmembrane protease serine-2 (TMPRSS2), and to a lesser extent, cathepsins, have been demonstrated to be present throughout the gastrointestinal tract, thus facilitating viral entry and pathogenesis. Furthermore, multiple reports have demonstrated evidence of viral shedding outside the nasopharynx, including the stool, for prolonged time periods even in the absence of detection of viral RNA in the nasopharynx. As such, testing for SARS-CoV-2 in stool samples with reverse transcription polymerase chain reaction (RT-PCR) assays for detection of viral RNA could aid in identifying patients that lack classic respiratory symptoms, present with atypical symptoms, or in those with a high index of suspicion (e.g. elevated inflammatory markers), but test negative on the classic nasopharyngeal swab. Furthermore, this underscores the potential for atypical transmission, with a focus on fecal-oral transmission and the need for strict hand hygiene.