Diarrhea may be underestimated: a missing link in 2019 novel coronavirus

Weicheng Liang; Zhijie Feng; Shitao Rao; Cuicui Xiao; Zexiao Lin; Qi Zhang; Wei Qi

Interestingly, when we examined expression profiles of another two virus receptors (ANPEP receptor for HCoV-229E virus and DPP4 receptor for MERS-CoV virus), we found that the RNA levels of these two virus entry receptors were also highly expressed in proximal or distal enterocytes ( Figure 2E-H) , consistent with the expression profile of ACE2. As these three virus receptors (ACE2, ANPEP, and DPP4) displayed significantly overlapped expression profiles, it is possible that the human intestinal tract may serve as an alternative infection route for these viruses. In this study, we displayed that ACE2 was highly expressed in the small intestine, especially in proximal and distal enterocytes. Interestingly, another group has recently reported similar expression pattern in human small intestine one day before our submission 13 . It has been characterized that enterocytes are directly exposed to food and foreign pathogens. Interestingly, other virus receptors like DPP4 displayed similar expression patterns as ACE2 in the small intestine. DPP4 is a known receptor for MERS-CoV through interacting with the S1 subunit of MERS-CoV spike protein. It has been reported that ACE2 controls intestinal inflammation and diarrhea. Therefore, mutual interaction between 2019-nCoV and ACE2 might disrupt the function of ACE2 and results in diarrhea or other gastrointestinal symptoms. According to the data analysis of three recent reports, we compared the incidence of various symptoms from infected patients and found that the incidence of diarrhea significantly differed in different reports. As 2019-nCoV is highly homologous to that of SARS-CoV, and it has been reported that around 20-25% of SARS patients have diarrhea 14 , it is confusing to observe the relatively low incidence (2-3%) of diarrhea in two cohorts from hospitals in Wuhan. If the incidence of diarrhea is underestimated, the reasons may because it is sometimes challenging to diagnose diarrhea since we still do not have a precise criterion for it. The definition of diarrhea by the World Health Organization is having three or more loose or liquid stools per day or having more stools than a person's health condition. To a certain extent, this criterion is subjective.