By IDSE News Staff
Along with the unpleasant aches, fever, sore throat and other respiratory symptoms that may accompany COVID-19 infection, up to half of people will experience diarrhea. Some 30% of them will develop long COVID, a persistent infection marked by debilitating symptoms, including chronic pain, brain fog, shortness of breath, chest pain and intense fatigue.
New research suggests the inflammation linked to COVID-19 diarrhea may be similar to the inflammatory effects of COVID-19 in the lungs and other parts of the body, and this inflammatory response in the gut may linger putting people at risk for long COVID.
“While COVID-19 diarrhea is not life-threatening like cholera, it can often predict a severe case and also who gets the long-COVID syndrome,” said Mark Donowitz, MD, an emeritus professor of medicine and physiology at the Johns Hopkins University School of Medicine, in Baltimore.
To determine the mechanism by which COVID-19 diarrhea occurred, Dr. Donowitz and his team used a model of normal human intestines called enteroids. Formed by stimulating human stem cells to develop into many of the cells lining the intestine, enteroids form a single layer of cells in a petri dish oriented in the same direction as the normal intestine.
The research team exposed the enteroids to live SARS-CoV-2 virus and saw changes in the gut cells’ protein expression and function (Cell Mol Gastroenterol Hepatol 2024 Jul 30. doi:10.1016/j.jcmgh.2024.101383).
In typical diarrhea caused by bacterial infections, viruses or medication side effects, there are changes in transport proteins that move molecules across cell membranes. These changes inhibit sodium and chloride absorption and produce chloride secretion. In COVID-19 diarrhea, both effects occurred, which is common in diarrheal diseases. Unlike many diarrheal diseases, a different class of proteins—called calcium-activated chloride channels—were involved in the chloride secretion in COVID-19 diarrhea. While many diarrheal diseases are caused either by direct effects on the transport proteins or by the accompanying inflammation, Dr. Donowitz and his team saw a combination of the two in the enteroid cells exposed to SARS-CoV-2.
This evidence suggests that testing the role of inhibitors of this response may be a way to treat COVID-19 diarrhea.
“The precise mechanisms of long COVID are a big mystery, although we now know that the virus can persist in the intestine for a long time,” Dr. Donowitz said. “The next big question is to determine what exactly allows the virus to live in the intestine and what allows the virus to live over a long period.”
This research was supported in part by the Johns Hopkins University School of Medicine Dean Durso Award and the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases.
