Most of us are familiar with COVID-19’s hallmark symptoms of a loss of taste or smell and difficulty breathing, but a full 60 percent of patients infected with SARS-CoV-2 also report gastrointestinal symptoms such as nausea, diarrhea, and stomach pain.
Infection of the gut, which expresses high levels of the ACE2 receptor protein that SARS-CoV-2 uses to enter cells, is correlated with more severe cases of COVID-19, but the exact interactions between the virus and intestinal tissue is difficult to study in human patients. Animal models, while useful, do not fully reflect how human organs react to infection by pathogens.
To solve that problem, a team of scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University and several other Wyss partner organizations in Boston used a human Intestine Chip previously developed at the institute to study coronavirus infection and potential treatments in an environment that mimics the human intestine more effectively than cells grown in a dish.
They infected the Intestine Chip with a coronavirus called NL63 that causes the common cold and, like SARS-CoV-2, uses the ACE2 receptor to enter cells, and then tested the effects of various drugs that have been proposed for treating SARS-CoV-2 infection.
The scientists found that a drug called nafamostat reduced infection while the drug remdesivir, which has been used to treat COVID-19 patients, did not reduce infection and actually damaged the intestinal tissue. This new preclinical model, which could be used to identify drugs that can target GI symptoms associated with both the common cold and SARS-CoV-2 virus infections in the future, is described in Frontiers in Pharmacology.
Toxic treatment
The Intestine Chip is about the size of a USB memory stick made of a clear, flexible polymer through which run two parallel channels: one lined with human blood vessel cells, the other with human intestinal lining cells. A permeable membrane between the two channels ensures that the cells can exchange molecular messengers, and that substances can be delivered into the blood via the gut, mimicking digestion. The tissues in the Intestine Chip are repeatedly stretched and released to recreate the rhythmic movements caused by muscle contractions in the GI tract.