COVID-19 in the GI tract

New data in press in Gastroenterology by Fei Xiao, et al at Sun Tat-sen University in Zhuhai, China indicate that COVID-19 can be identified in the GI tract, even after respiratory samples become negative for SARS-CoV-2.

This comes after a separate case report in NEJM by Michelle Holshue, et al on January 31 detailed the first known US case of COVID-19; a 35 year-old man in Washington State who had been to Wuhan China visiting family presented to urgent care on January 19 with 4 days of cough and fever, 2 days of nausea and vomiting, and tested positive for SARS-CoV-2 by oro- and nasopharyngeal swabs. On day 2 of admission he reported abdominal pain and loose stools, which were sampled and tested positive by rRT-PCR for SARS-CoV-2. Of particular fascination, his serum did not.

The Xiao study coupled the Holshue report with recent news in Nature from Zhou, et al indicating that SARS-CoV-2 uses the ACE2 enzyme for viral entry (previously seen in SARS and HCoV-NL63, a different strain of human coronavirus) and older work from Harmer, et al in 2002 that ACE2 mRNA is expressed in the GI tract, and from Yan, et al in 2020 that ACE2 as a cell receptor requires presence of, and is stabilized by, B(0)AT1. Stool samples from 73 of 73 infected hospitalized patients (ages <1 to 78 years) in Xiao's study tested positive for SARS-CoV-2 RNA. Immunofluorescence revealed abundant expression of ACE2 in gastric, duodenal and rectal glandular cells, while H&E stain showed substantial inflammatory cell infiltration in specimens obtained on endoscopy multiple patients.

In light of CDC guidance for discontinuation of Transmission-Based Precautions after two consecutive pairs of oro- and nasopharyngeal specimens collected ≥24 hours apart have returned negative, Xiao's most concerning finding is that despite conversion to negative testing in respiratory tract samples, > 20% of their patients' fecal samples persisted testing positive for viral RNA. This is one of many examples reflecting the ongoing need to update guidance as information emerges.

You can find the entire AGA blog post used as the basis of this entry here.

(Image from: Xiao F et al, https://doi.org/10.1053/j.gastro.2020.02.055)

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Sources:

1. Novak, K. COVID-19 Detected in Gastrointestinal Tract and Feces. AGA Journals (2020). https://journalsblog.gastro.org/covid-19-detection-in-the-gastrointestinal-tract-and-feces/

2. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H, Evidence for gastrointestinal infection of SARS-CoV-2, Gastroenterology (2020). doi: https://doi.org/10.1053/j.gastro.2020.02.055

3. Holshue, M. L. et al. First Case of 2019 Novel coronavirus in the United States. N. Engl. J. Med (2020) https://doi.org/10.1056/NEJMoa2001191

4. Zhou, P., Yang, X., Wang, X. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7

5.Harmer, D., et al. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS PRESS 532, 1-2 (2002). https://doi.org/10.1016/S0014-5793(02)03640-2

6. Yan, R, et al. Structural basis for the recognition of the 2019-nCoV by human ACE2, bioRxiv (2020). https://www.biorxiv.org/content/10.1101/2020.02.19.956946v1