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SARS-CoV-2 has resulted in numerous cases of Coronavirus Disease 2019 (COVID-19) worldwide. In addition to fever and respiratory symptoms, digestive symptoms also are observed in some patients with COVID-19. Angiotensin-converting enzyme 2 (ACE2) was reported to be the receptor for SARS-CoV-2. The aim of this study was to comprehensively investigate the digestive symptoms that occur in COVID-19 patients, and the potential pathogenic route of the SARS-CoV-2 infection in digestive tract organs (from the oral cavity to the gastrointestinal tract). We investigated the digestive symptoms of 48 patients with COVID-19 and explored ACE2 expression in digestive tract and lung cancers, based on a series of bulk and single-cell RNA sequencing data obtained from public databases. We found that 25% (12/48) of the patients with COVID-19 suffered from digestive symptoms, among which pharyngalgia (7/48) was the most common manifestation, followed by diarrhea (3/48), anorexia (3/48), and nausea (1/48). The bulk tissue RNA sequencing analysis indicated that digestive tract organs had higher ACE2 expression levels compared to the lung, and the expression of ACE2 in the lung increased with age. Single-cell RNA-Seq results showed that the ACE2-positive-cell ratio in digestive tract organs was significantly higher compared to the lung. ACE2 expression was higher in tumor cells compared to normal control (NC) tissues. While in gastric tissues, ACE2 expression gradually increased from chronic gastritis to metaplasia, to early cancer. Our data might provide a theoretical basis for screening the SARS-CoV-2 susceptible population and for the clinical classification of treatment of patients with COVID-19.

Digestive symptoms of COVID-19 and expression of ACE2 in digestive tract organs