Larazotide works by tightening the junctions between cells in the intestinal lining, making the intestine less permeable. Yonker explains that it has been studied and tested extensively, especially for celiac disease, and has an excellent safety profile. “So we thought it would be justified to try larazotide in long Covid.”
Yonker and his colleagues will administer larazotide to 32 patients between the ages of 7 and 21, who will take the drug for eight weeks; another 16 patients will receive a placebo. To participate in the trial, patients must have a detectable presence of the covid-19 “spike” protein in their blood. The intention is to check whether reducing intestinal permeability can make an appreciable difference in the symptoms and quality of life of young patients.
Carrying out a test of this type has not been easy
“It started last year, but we had to put it on pause for a few months due to staffing and drug supply issues,” Yonker recalls, “One of the requirements is that we have to make sure that the spike protein is present in the blood, which “It may involve multiple blood draws from these children, which takes time. So I think it will take another one to two years to recruit all the patients we need, but I would love to move faster.”
The results, when they come to light, will help researchers determine whether leaky gut is likely to be a major cause of the disease in at least a subset of patients, and whether larazotide should be tested more widely as a potential treatment.
There could be other conditions related to the intestine. Brodin believes that in some children, the virus remains in the intestine rather than being completely excreted, allowing it to actively damage the intestinal wall and contribute to gastrointestinal problems. He suspects that this viral persistence may induce an autoimmune reaction in the bloodstream, causing more symptoms.
The Yonker trial is also encouraging other pediatric researchers from long covid to start their own trials, exploring other theories behind the condition. Danilo Buonsenso, a pediatrician at Gemelli University Hospital in Rome who led the first study which examined whether children developed long covid, described the study as fascinating. Now he is trying to get funding for an ambitious trial testing multiple treatments.
Buonsenso’s work includes studies which suggest that blood clots, as well as inflammation within the lining of blood vessels known as “endothelium”, may play a role in triggering certain symptoms. On the other hand, he led a study in which it was discovered that some children with long Covid also suffer from a disorder called postural tachycardia syndrome (POTS) that also affects many adults with long covid.
“In my opinion, there will not be a single drug that solves long covid, since multiple things are being documented,” he says. “We need to investigate the role of low-dose anticoagulants with known effects in reducing endothelial inflammation. But we also need to look at drugs specific for POTS and drugs specific for neurocognitive symptoms, such as chronic pain and headache “
Meanwhile, Yonker’s focus on the gut represents a crucial first step. Given the desperation of children suffering from this disease and their parents, she is hopeful that, if her trial is successful, it will provide an evidence-based, child-specific treatment option: “I think it’s extremely important to advocate for advances in the treatment of children with long Covid, rather than waiting for drip guidance, based on what we see in adult trials,” he concludes.
Article originally published in WIRED. Adapted by Mauricio Serfatty Godoy.