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 qualify for the trial, patients must have a detectable presence of the Covid-19 Spike protein in their blood. The intention is to see if reducing intestinal permeability can make a noticeable difference in symptoms and quality of life in young patients.
Carrying out a test of this type has not been easy. “It started last year, but we had to put it on hold for a few months due to staffing and drug supply issues,” Yonker says. “One of the requirements is that we have to make sure that the spike protein is present in the blood, which may involve multiple blood draws from these children, which takes time. Because of this, I expect it will take us another year or two to recruit all the patients we need, but I would love to move faster.”
The results, when they emerge, will help researchers determine whether leaky gut is likely to be a major cause of disease in at least a subset of patients, and whether larazotide should be tested more widely as a potential treatment.
There could be other gut-related implications: Brodin believes that in some children, the virus remains in the gut 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 long Covid researchers 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 Examining whether children were developing long Covid, he described the study as fascinating. He is now trying to get funding for an ambitious trial testing multiple treatments.
Buonsenso’s work includes studies suggesting that blood clots, as well as inflammation within the lining of blood vessels known as endothelium, may play a role in the appearance of certain symptoms. Furthermore, he led a study that found that some children had long Covid. also fight with a condition called postural tachycardia syndrome (POTS) which also affects many adults with long Covid.
“In my opinion, there will not be a single drug that will solve Covid in the long term, 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 should also look for medications specific to POTS and medications specific to neurocognitive symptoms like chronic pain and headache.”
Meanwhile, Yonker’s focus on the gut represents a crucial first step. Given the desperation of children suffering from the condition and their parents, she is hopeful that if her trial is successful, it will provide an evidence-based treatment option specifically for children. “I think it is extremely important to advocate for timely advances in the treatment of children suffering from long Covid rather than waiting for guidance, based on what we see in trials in adults,” he says.