SARS-CoV-2 infects human intestinal epithelial cells

Last Updated: 2020-05-07

By Will Boggs MD

NEW YORK (Reuters Health) - SARS-CoV-2, the coronavirus that causes COVID-19, productively infects enterocytes in human small intestinal organoids (hSIOs), researchers in the Netherlands report.

"Our findings confirm suspicions described in multiple clinical papers on patients (particularly children) with gastrointestinal symptoms," said Dr. Hans Clevers of the Royal Netherlands Academy of Arts and Sciences and University Medical Center, in Utrecht.

"Our study shows that the virus can directly target the lining of the gut. This may be of particular importance as it implies a second (oral-fecal) route of transmission, in addition to the dominant respiratory route," he told Reuters Health by email.

Dr. Clevers and colleagues investigated the ability of SARS-CoV-2 to infect human intestinal enterocytes using hSIOs.

These enterocytes were readily infected by SARS-CoV-2 and by SARS-CoV, the virus associated with the 2003 SARS outbreak, as demonstrated by confocal- and electron-microscopy, the team reports in Science.

Viral particles occurred at both the basolateral and apical side of enterocytes.

Infection of these cells with SARS-CoV-2 elicited a range of cytokines and interferon-stimulated genes, a phenomenon that has been reported with infections by other viruses.

SARS-CoV-2 appeared to induce a stronger interferon response than SARS-CoV in these organoids.

Infection rates were similar in enterocyte precursors and enterocytes. Because expression of the ACE2 enzyme used by SARS-CoV-2 to infect cells increases about 1,000-fold upon differentiation, this suggests that low levels of ACE2 may be sufficient for viral entry.

"The approach to use gut organoids to study the virus opens up future research on this and other viruses in animals (think of bats, pangolins, big cats, etc.)," Dr. Clevers said. "For most of these species, no lab models exist. Yet, gut organoids can be grown from any mammalian species tried so far. It just requires a 1 mm piece of tissue from the pertinent animal to create an ever-expanding organoid line that can be shared with any lab around the world."

Dr. Klaus Moenkemueller from Ameos Klinikum, in Halberstadt, Germany, who recently reviewed the interaction of SARS-CoV-2 with enterocytes and its potential clinical implications, told Reuters Health by email, "This study is the first to confirm active entry of SARS-CoV-2 into the enterocyte. Very surprisingly, the authors also detected viral invasion at both the apical as well as on the basolateral side. The small bowel likely represents an important entry site for SARS-CoV-2, either from the luminal side or through the circulation."

"The report brings us a step closer to understanding the invasiveness and tropism of SARS-CoV-2, showing that it is likely an entero-respiratory virus, like other coronaviruses," he said. "The clinical findings we were observing in COVID-19 make sense, now that we know that SARS-CoV-2 can actively infect enterocytes."

SOURCE: https://bit.ly/2WaCch2 Science, online May 1, 2020.