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TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes

Our take —

This study suggests that while SARS-CoV-2 does infect the intestinal epithelium cells, it is highly unlikely that it is transmitted via the fecal-oral route.

Study design


Study population and setting

All human cell samples were derived from de-identified tissue collected with informed consent from healthy subjects who were undergoing colonoscopy at Stanford University or Washington University School of Medicine

Fecal samples were collected from patients with COVID-19. Patient populations are not described.

Summary of Main Findings

The authors demonstrated that angiotensin-converting enzyme 2 (ACE2), a known receptor for mediating SARS-CoV-2 entry, is expressed to high levels in cells in the small intestine in both humans and mice and that a Vesicular Stomatisi Virus pseudo-typed with SARS-CoV-2 S protein (which mediates entry via interaction with ACE2) as well as a clinical isolate of SARS-Cov-2 was able to infect these cells.

Additionally, it was demonstrated that the serine proteases TMPRSS2 and TMPRSS4 help to mediate SARS-CoV-2 entry.

The authors also demonstrated that while small levels of infectious SARS-CoV-2 were detectable following incubation in simulated gastric fluid, there was no detectable virus following incubation in simulation colonic fluid.

Importantly, while viral RNA was detected in 3 of 10 fecal samples from infected persons, no infectious virus was detected in any of the samples.

Study Strengths

This study provides extensive evidence using multiple methods that SARS-CoV-2 is able to infect the intestinal epithelium cells.


While this study is highly suggestive that SARS-CoV-2 cannot be transmitted via the fecal-oral route, the patient population size of 10 id quite limited. Larger studies should be performed to confirm that infectious virus is not found in fecal material.

Value added

This study is highly suggestive that SARS-CoV-2 cannot be transmitted via the fecal-oral route,

Additionally, the serine proteases TMPRSS2 and TMPRSS4 may be new targets for therapeutics as they were identified here as important for efficient entry of SARV-CoV-2.