Infection with COVID-19 causes respiratory illnesses including severe respiratory syndrome (SARS), so it infects respiratory epithelial cells and spreads via respiratory tract. However, the viral target cells and organs have not been fully determined.
COVID-19 enters cells via the angiotensin I converting enzyme 2 (ACE2), which is highly expressed in the gastrointestinal system. Fei Xiao et al therefore searched for COVID-19 in feces from 73 infected patients (ages 10 months to 78 years, 25 male and 14 female) during their hospitalization, and viral RNA and viral nucleocapsid protein in gastrointestinal tissues from 1 of the patients.
Stool samples from all 73 infected hospitalized patients tested positive for COVID-19 RNA. Lamina propria of stomach, duodenum, and rectum contained numerous infiltrating plasma cells and lymphocytes, with interstitial edema.
The COVID-19 nucleocapsid protein was detected in the cytoplasm of gastric, duodenal, and rectum glandular epithelial cells, but not in esophageal epithelium. Gastrointestinal epithelial cells (glandular cells of gastric, duodenal and rectal epithelia) were also positive for ACE2.
Xiao et al conclude that these findings provide evidence for gastrointestinal infection of COVID-19 and a possible fecal to oral route of transmission.
The authors state that ACE2 was only rarely detected in esophageal mucosa, probably because esophageal epithelium is composed mainly of squamous epithelial cells, which express lower levels of ACE2 than glandular epithelial cells.
Xiao et al propose testing for COVID-19 RNA in feces by real-time reverse transcriptase PCR (RT-PCR), to monitor infectious virions released from gastrointestinal tract.
According to CDC guidance for patients with COVID-19, the decision to discontinue transmission-based precautions for hospitalized patients is based on negative results from RT-PCR tests of at least 2 sequential respiratory tract specimens collected at least 24 hours apart. However, Xiao et al found that more than 20% of patients with positive fecal samples feces had a negative result for RNA in respiratory tract. These findings indicate that gastrointestinal infection and the potential fecal to oral transmission can occur after viral clearance from respiratory tract.
In a commentary article also in Gastroenterology, Jinyang Gu et al write that ACE2 inhibitors might be developed for treatment or prevention of COVID-19 infection.
Gu et al add that COVID-19 infection also causes mild to moderate liver injury, including increased levels of aminotransferases, hypoproteinemia, and prothrombin time. As many as 60% of patients with SARS had liver impairment and the virus has been detected in liver tissue. Single cell RNA sequence data from 2 independent cohorts revealed expression of ACE2 mRNA in 59.7% of cholangiocytes but only 2.6% of hepatocytes. So COVID-19 might lead to direct damage of intrahepatic bile ducts.