**The Initial Clinical Trials for Children with Long COVID Are Commencing**
Four years after the onset of the COVID-19 pandemic, the healthcare sector continues to confront the prolonged repercussions of the virus, especially in pediatric populations. While adults suffering from long COVID frequently describe symptoms like exhaustion and cognitive fog, children face a distinct array of ongoing challenges. A recent investigation indicates that preteens are more susceptible to issues such as headaches, abdominal discomfort, sleep irregularities, and focus challenges. These symptoms vary with age, with younger children exhibiting fewer indications of organ impairment compared to teenagers, who generally show symptoms more akin to those seen in adults.
In spite of the notable consequences of long COVID on children, the research into this condition remains sparse, primarily depending on online questionnaires, parental interviews, and electronic health data. This is alarming, as studies indicate that between 10 and 20 percent of children might develop long COVID following an acute infection. Some children continue to experience illness even three years post-infection, underscoring the pressing need for more focused research and therapeutic strategies.
### A Groundbreaking Clinical Trial for Pediatric Patients
In an encouraging turn of events, the first clinical trial specifically targeting children and young adults affected by long COVID has been initiated. This trial is seeking participants aged between 7 and 21, exploring a possible treatment that builds on findings connecting long COVID in children to gut health.
Dr. Lael Yonker, a pediatric pulmonologist at Massachusetts General Hospital in Boston, is leading the trial. Yonker’s previous research on multisystem inflammatory syndrome in children (MIS-C)—a severe, acute form of long COVID—revealed that children diagnosed with MIS-C had increased levels of a protein called zonulin. Zonulin is linked to heightened intestinal permeability, commonly known as “leaky gut.” This phenomenon permits viral particles from SARS-CoV-2 to leak from the intestines into the bloodstream, potentially causing extensive inflammation.
### The Impact of Larazotide
Dr. Yonker’s prior study also identified a potential treatment: a medication named larazotide. This drug is currently used for treating leaky gut-related ailments, including celiac disease. In her findings, children with MIS-C administered larazotide showed decreased levels of viral particles in their bloodstream and reported symptomatic relief.
Larazotide functions by reinforcing the connections between cells in the intestinal lining, thereby decreasing gut permeability. Considering its safety and promising outcomes in MIS-C cases, Yonker and her team opted to evaluate larazotide in children with long COVID.
The trial will include 32 patients who will receive larazotide over eight weeks, while an additional 16 participants will be given a placebo. To be eligible, participants must have detectable levels of the COVID-19 spike protein in their blood. The aim is to assess whether reducing intestinal permeability can relieve long COVID symptoms and enhance the quality of life for these young individuals.
### Hurdles and Future Outlook
Conducting the trial has presented several challenges. Yonker mentions that the trial faced a temporary halt due to issues with staffing and drug availability. Furthermore, the need to confirm the presence of the spike protein in the blood has hindered participant recruitment, as it usually requires multiple blood tests from the children. Yonker anticipates that it may take an additional one to two years to recruit all necessary subjects, though she remains optimistic about the valuable insights the trial may offer.
Should the trial succeed, it could provide evidence that a leaky gut is a significant contributor to long COVID for at least some patients. Additionally, it may lead to broader testing of larazotide as a treatment alternative.
### Exploring Other Theories and Continued Research
Yonker’s research is inspiring fellow scientists to investigate various dimensions of long COVID in children. For instance, Dr. Petter Brodin, a pediatric immunology professor at Imperial College London, suggests that, in certain instances, the virus might persist in the gut, damaging the intestinal lining and leading to gastrointestinal issues. This viral persistence could potentially prompt an autoimmune response, resulting in supplementary symptoms.
Dr. Danilo Buonsenso, a pediatrician at Gemelli University Hospital in Rome, is also studying long COVID in the pediatric demographic. His research hints that blood clotting and inflammation of the blood vessel lining (endothelium) may be implicated in manifesting specific symptoms. Buonsenso is currently seeking funding for a comprehensive trial aimed at testing multiple interventions, including low-dose anticoagulants to mitigate endothelial inflammation and targeted medications for conditions such as postural tachycardia syndrome (POTS), which affects both children and adults suffering from long COVID.
### A Comprehensive Treatment Strategy
Buonsenso underscores that it is improbable there will be a singular medication that can treat long COVID, considering the condition seems to involve various physiological mechanisms. He promotes a holistic treatment approach addressing blood vessel inflammation, neurocognitive issues, and chronic pain.
Nonetheless, Yonker’s emphasis on gut health is a vital initial step towards unraveling and addressing long COVID in children.
