Johns Hopkins Medicine scientists have identified key molecular mechanisms driving COVID-19-related diarrhea using innovative “mini intestine” models. This breakthrough offers a pathway to potential treatments and enhances our understanding of long COVID-19.
Researchers at Johns Hopkins Medicine have made significant strides in understanding the molecular underpinnings of COVID-19-related diarrhea, offering hope for new treatments and insights into long COVID-19. Using advanced models that simulate human intestines, the team has uncovered several mechanisms causing this debilitating symptom.
The study, published in Cellular and Molecular Gastroenterology and Hepatology, utilized enteroids, miniature versions of human intestines grown from stem cells. These “mini intestine-in-a-dish” models helped the team observe how SARS-CoV-2, the virus responsible for COVID-19, alters protein function in gut cells.
“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,” Mark Donowitz, Emeritus Professor of Medicine and Physiology at Johns Hopkins University School of Medicine, said in a news release.
The researchers found that COVID-19-related diarrhea shares some commonalities with other diarrheal illnesses, involving disrupted sodium and chloride absorption and increased chloride secretion. Notably, the team identified that calcium-activated chloride channels, rather than proteins associated with cystic fibrosis, were driving the chloride secretion in this instance.
An unusual discovery was that COVID-19 diarrhea results from a combination of direct effects on transport proteins and inflammation — a dual mechanism not commonly observed in other diarrheas.
The team hypothesizes that the inflammatory response in COVID-19 diarrhea may mirror the inflammation seen in the lungs and other organs affected by the virus, suggesting that anti-inflammatory treatments could be beneficial.
“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,” added Donowitz. “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 of time.”
This groundbreaking research, backed by the Johns Hopkins University School of Medicine and the National Institutes of Health, also holds promise for addressing long COVID-19, a condition affecting a significant number of those who recover from the virus.
The study’s co-authors include a collaborative team from Johns Hopkins Medicine, the Johns Hopkins Bloomberg School of Public Health and the University of New Mexico Health Sciences Center, among others. Their collective work provides not only a deeper understanding of a pressing COVID-19 symptom but also a foundation for future therapeutic strategies.