Researchers from the Hubrecht Institute in Utrecht, Erasmus MC University Medical Center Rotterdam, and Maastricht University in the Netherlands have found that SARS-CoV-2 can infect cells of the intestine and multiply there. The researchers successfully propagated the virus in vitro and monitored the response of the cells to the virus. They used state-of-the-art cell culture models of the human intestine. They have provided a new cell culture model for the study of COVID-19. Perhaps this observation in Holland suggests why about 33% of COVID-19 patients experience gastrointestinal symptoms such as diarrhea, and the fact that the virus has often be detected in stool samples.
Published in the recent version of Science on the 1st of May 2020, the researchers sought to understand the phenomena that nearly 33% of patients experience gastrointestinal symptoms from nausea and diarrhea to abdominal plains. Moreover, the virus can be detected in human stool long after primary respiratory symptoms have been resolved. This suggests that the virus can also spread via so-called “fecal-oral transmission.”
Key Similarities between Respiratory and Gastrointestinal Organs
Although they may seem quite different, there are some similarities between these organs. One similarity of note is the presence of the ACE2 receptor, the receptor through which the COVID-19 causing SARS-CoV-2 virus can enter the cells. The inside of the intestine is loaded with ACE receptors. Until now it was basically unknown whether intestinal cells could actually become infected and produce virus particles.
Intestinal Organoids Used
The team from Hubrecht Institute, Erasmus MC and Maastricht University used human intestinal organoids: tiny versions of the human intestine that can be grown in the lab. Hans Clevers (Hubrecht Institute) noted, “These organoids contain the cells of the human intestinal lining, making them a compelling model to investigate by SARS-CoV-2.
Once the researchers developed the organoids and added the virus to the organoids they found they were rapidly infected. The SARS-CoV-2 virus enters a subset of the cells in the intestinal organoids, and the number of cells that are infected increases over time. Using an electron microscopy, an advanced way to visualize the different compounds of the cell in great detail, the researchers found virus particles inside and outside the cells of the organoids. As the lockdown was ongoing, the researchers were able to collaborate from their home offices, studying the infected organoids via virtual slides.
Interferon Genes Activate
The Dutch team then investigated the response of the intestinal cells to the virus using RNA sequencing, a method to study which genes are active in the cells. This revealed that so-called interferon stimulated genes are activated. Known to combat viral infection, any future research will focus on these gene more carefully—how they can be used to develop new treatments.
The team also found that, to their surprise, the virus infected cells with both high and low levels of the ACE2 receptor. Hopefully these studies can lead to new ways to block the entry of the virus into human cells.
What are the Implications of this Study?
SARS-CoV-2 can multiply in cells of the gastrointestinal track, suggests the researchers. But the investigators are not sure if SARS-CoV-2 located in the intestines of COVID-19 patients plays any role in transmission, reported Bart Haagman with Erasmus MC. Perhaps these findings may lead to the conclusion at some point that those patients with gastrointestinal symptoms need some special attention. However, more extensive testing will be required.
Bart Haagman, PhD Erasmus Medical Center, Rotterdam, Netherlands.
Hans Clevers, PhD, Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.
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Call to Action: The researchers continue their ongoing collaboration—now studying the differences between infections in the lung and the intestine by comparing lung and intestinal organoids infected with SARS-CoV-2.