In a new study, researchers have found that the coronavirus SARS-CoV-2, which causes COVID-19, can infect cells of the intestine and multiply there.
Using state-of-the-art cell culture models of the human intestine, the researchers monitored the response of the cells to the virus, providing a new cell culture model for the study of COVID-19.
These findings could explain the observation that approximately one-third of COVID-19 patients experience symptoms such as diarrhea, and the fact that the virus often can be detected in stool samples.
The research was conducted by a team from the Hubrecht Institute in Utrecht in the Netherlands and elsewhere.
Patients with COVID-19 show a variety of symptoms linked to respiratory organs—such as coughing, sneezing, shortness of breath, and fever—and the disease is transmitted via tiny droplets that are spread mainly through coughing and sneezing.
One-third of the patients however also have gastrointestinal symptoms, such as nausea and diarrhea.
In addition, the virus can be detected in human stool long after the respiratory symptoms have been resolved.
This suggests that the virus can also spread via so-called “fecal-oral transmission”.
Though the respiratory and gastrointestinal organs may seem very different, there are some key similarities.
A particularly interesting similarity 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 ACE2 receptors. However, until now it was unknown whether intestinal cells could actually get infected and produce virus particles.
In the study, the team set out to determine whether the SARS-CoV-2 virus can directly infect the cells of the intestine, and if so, whether it can replicate there as well.
They used human intestinal organoids: tiny versions of the human intestine that can be grown in the lab.
When the researchers added the virus to the organoids, they were rapidly infected. The virus enters a subset of the cells in the intestinal organoids, and the number of cells that are infected increases over time.
Using electron microscopy, an advanced way to visualize different components of the cell in great detail, the researchers found virus particles inside and outside the cells of the organoids.
The researchers then tested the response of the intestinal cells to the virus with RNA sequencing, a method to study which genes are active in the cells.
This revealed that so-called interferon-stimulated genes are activated.
These genes are known to combat viral infection. Future work will focus on these genes more carefully, and on how they could be used to develop new treatments.
In the meantime, the researchers are continuing their collaboration to learn more about COVID-19.
They are studying the differences between infections in the lung and the intestine by comparing lung and intestinal organoids infected with SARS-CoV-2.
One author of the study is Hans Clevers (Hubrecht Institute).
The study is published in Science.
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