Reply

Abstract

We appreciate the positive response from Dr El Hajra Martínez and others to our study regarding gastrointestinal (GI) infection and fecal–oral transmission of coronavirus disease 2019 (COVID-19).1Xiao F. et al.Gastroenterology. 2020; 158: 1831-1833Abstract Full Text Full Text PDF PubMed Scopus (1750) Google Scholar, 2El Hajra Martínez I. et al.Gastroenterology. 2020; 159: 1624-1625Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 3Uno Y. Gastroenterology. 2020; 159: 1622-1623Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 4Bonato G. et al.Gastroenterology. 2020; 159: 1621-1622Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar, 5Garg M. et al.Gastroenterology. 2020; 159: 1623-1624Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Our study presented evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the stomach, duodenum, and rectum from a severe case of COVID-19.1Xiao F. et al.Gastroenterology. 2020; 158: 1831-1833Abstract Full Text Full Text PDF PubMed Scopus (1750) Google Scholar We also isolated infectious SARS-CoV-2 from the patient’s stool.6Xiao F. et al.Emerg Infect Dis. 2020; 26: 1920-1922Crossref PubMed Scopus (329) Google Scholar El Hajra Martínez et al detected SARS-COV-2 RNA in ileal tissue, supplementing another piece of evidence of GI infection of SARS-CoV-2. In our follow-up study, where endoscopy was performed on 20 patients with COVID-19, immunofluorescence staining on section of GI tissue specimen showed expression of intracellular viral nucleocapsid protein in ileal epithelium. These results demonstrated that SARS-CoV-2 can infect ileum mucosa (unpublished data). And some COVID-19 patients tested negative for viral RNA in stool showed positivity in GI tissue, which was in line with the findings from El Hajra Martínez. These observations indicated replication of SARS-CoV-2 in the GI epithelium. However, the dilution of the released virions in stool made its detection there less sensitive than in GI tissue. Therefore, it is necessary to test viral RNA or viral protein expression in GI tissue biopsies to confirm the related infection. El Hajra Martínez et al observed GI infection in a mild case of COVID-19. The data from our follow-up study showed that 87.5% of patients with GI infection had mild symptoms, whereas 12.5% of them evolved into severe phases (unpublished data), demonstrating the occurrence of GI infection in both mild and severe cases. The ileal thickening from a computed tomography scan reported by El Hajra Martínez et al can be explained by our observation of GI pathology, which is characterized by infiltration of plasma cells and lymphocytes with interstitial edema in the GI tissue.1Xiao F. et al.Gastroenterology. 2020; 158: 1831-1833Abstract Full Text Full Text PDF PubMed Scopus (1750) Google Scholar,2El Hajra Martínez I. et al.Gastroenterology. 2020; 159: 1624-1625Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar We agree with Bonato et al4Bonato G. et al.Gastroenterology. 2020; 159: 1621-1622Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar in that personal protective equipment needs to be upgraded and provided to ensure the safety of all medical and nursing staff in the endoscopy team. Uno et al3Uno Y. Gastroenterology. 2020; 159: 1622-1623Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar calculated the average age of fecal viral RNA-positive and -negative populations from our study and speculated a correlation between fecal viral RNA and age-related changes in the gastric pH. As a matter of fact, immunofluorescence staining of viral nucleocapsid detected GI infection in 80% of our patients with COVID-19, regardless of age (unpublished data). Thus, it remains to be further investigated whether GI infection is related to gastric pH changes. Garg et al5Garg M. et al.Gastroenterology. 2020; 159: 1623-1624Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar proposed to further explore relationship between COVID-19, intestinal angiotensin-converting enzyme 2 expression, and GI symptoms. Our follow-up study showed that infection with SARS-CoV-2 in GI tract was dependent on the expression of both angiotensin-converting enzyme 2 and TMPRSS2 (unpublished data). To sum up, the results from our group and others showed that GI infection of SARS-CoV-2 is common in patients with COVID-19. SARS-COV-2 can infect the epithelium of the GI tract from the stomach to the rectum and release infectious virions on the surface of the mucosa. Fecal–oral and fecal–aerosol transmission routes of SARS-CoV-2 are highly possible. Further investigation on the transmission routes will have significant implications in taking preventative measures to stop the spread of SARS-CoV-2.