Expression of ACE2, TMPRSS2, and SARS-CoV-2 nucleocapsid protein in gastrointestinal tissues from COVID-19 patients and association with gastrointestinal symptoms

Background: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect the gastrointestinal (GI) tract in coronavirus disease 2019 (COVID-19) patients, the mechanism of GI tract injury is largely unknown. We aimed to study the potential factors that cause COVID-19 GI symptoms. Methods: We investigated the expression and co-localization of angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), SARS-CoV-2 nucleocapsid protein (NP), and the severity of inflammation in GI tissues from COVID-19 patients (n = 19) by immunofluorescence and histopathologic staining, and then studied their associations with GI symptoms. Results: Infected stomach tissues showed significantly higher ACE2 expression than uninfected ones, while infected duodenum tissues showed significantly higher TMPRSS2 expression than uninfected ones. The expression of TMPRSS2 exhibited a moderate correlation with viral NP across different GI tissues, while no significant association was observed between ACE2 and viral NP. Some GI symptoms such as diarrhea and nausea, were related to the expression level of ACE2, TMPRSS2 or the severity of inflammation. Furthermore, age and elevated aspartate transaminase were major risk factors for disease progression. Conclusions: ACE2 and TMPRSS2 were essential proteins in the SARS-CoV-2 infection of GI tract, while TMPRSS2 rather than ACE2 may play a more important role. GI symptoms may derive from the host receptor expression level and pro-inflammatory response in COVID-19 patients after viral infection of GI tissues, and further exacerbate the disease. So targeting TMPRSS2 and inflammation may represent an effective strategy for treating COVID-19 patients with GI symptoms.