Could the Gut Hold the Key to Treating Long Covid in Children?

As the world continues to grapple with the aftermath of the Covid-19 pandemic, one area of concern gaining attention is the long-term impact of the virus on children. While adults often report symptoms like fatigue and brain fog from long Covid, the condition appears to manifest differently in children. Emerging studies suggest that gut health may be a critical factor in understanding and treating long Covid in younger patients.

Understanding Long Covid in Children

Long Covid, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), refers to the prolonged symptoms some individuals experience after recovering from an initial Covid-19 infection. For children, the symptoms tend to differ from adults. Headaches, stomach pain, sleep disturbances, and attention issues are among the most commonly reported symptoms. A study from last month even revealed that younger children show fewer signs of organ damage, while adolescents exhibit symptoms more typical of adult cases.

Despite this, long Covid research in children remains limited. Although the U.S. National Institutes of Health (NIH) has invested over a billion dollars in long Covid research, much of the focus has been on adults. This is despite the fact that an estimated 10-20% of children who had Covid may develop long Covid. For some, the symptoms linger for years, affecting their quality of life and overall well-being.

A New Focus: The Role of the Gut

One groundbreaking area of research is investigating the gut’s role in long Covid. Researchers are increasingly looking at the gastrointestinal tract as a key player in the lingering symptoms experienced by some children. The theory is based on a phenomenon called “leaky gut,” where increased permeability in the intestines allows substances that shouldn’t enter the bloodstream to do so, leading to inflammation and other symptoms.

Dr. Lael Yonker, a pediatric pulmonologist at Massachusetts General Hospital, has been at the forefront of this research. In 2021, she conducted a study on multisystem inflammatory syndrome in children (MIS-C), a severe condition that can develop after Covid-19. Her research showed that children with MIS-C had elevated levels of a protein called zonulin, which indicates increased gut permeability. This “leaky gut” allowed viral particles to enter the bloodstream, triggering widespread inflammation.

As more children presented with long Covid symptoms, Dr. Yonker began to hypothesize that the same mechanism might be at play. Could the gut be the missing piece in understanding why some children struggle with persistent symptoms post-Covid?

A Possible Treatment: Larazotide

One of the more promising developments in the quest to treat long Covid in children involves the drug larazotide. Originally developed to treat celiac disease, larazotide works by tightening the junctions between cells in the intestinal lining, effectively reducing gut permeability.

In Dr. Yonker’s MIS-C study, children who received larazotide showed significant improvements. The drug reduced the levels of viral particles in their blood and alleviated some of their most severe symptoms. Given the safety profile of larazotide and its extensive study in other gastrointestinal conditions, Dr. Yonker believes it could be a viable treatment for long Covid in children.

To test this theory, she and her team have launched a placebo-controlled clinical trial. The trial, involving 32 children between the ages of 7 and 21, will administer larazotide for eight weeks. An additional 16 children will receive a placebo. The researchers will monitor the children to see if reducing gut permeability leads to improvements in their long Covid symptoms.

One of the challenges in running the trial has been the requirement to detect the Covid-19 spike protein in the children’s blood, which involves multiple blood draws. Despite these hurdles, Dr. Yonker is hopeful that the trial will provide much-needed answers. However, due to staffing and supply issues, the trial’s completion may take up to two more years.

Why the Gut Matters in Long Covid Research

The gut has long been known as a critical component of overall health. In the case of long Covid, it appears to play a particularly important role. Some researchers believe that in certain children, the Covid-19 virus may linger in the gut, even after other symptoms have subsided. This viral persistence can lead to ongoing damage to the intestinal wall, contributing to gastrointestinal issues. In turn, this may trigger an autoimmune reaction, where the body’s immune system starts attacking its own tissues, leading to a host of other symptoms.

This theory has prompted further investigation into gut-related treatments for long Covid. In addition to Dr. Yonker’s trial, other researchers are exploring potential therapies targeting the gut. Dr. Petter Brodin, a professor of pediatric immunology at Imperial College London, suggests that in some cases, long Covid may be driven by viral particles escaping the gut and causing inflammation elsewhere in the body.

Other Approaches to Treating Long Covid in Children

While gut-focused treatments are promising, researchers caution that long Covid is a complex condition. Dr. Danilo Buonsenso, a pediatrician at Gemelli University Hospital in Rome, points out that there may not be a single solution to the problem. His studies suggest that inflammation in the lining of blood vessels, as well as blood clots, could also contribute to long Covid symptoms.

In fact, Dr. Buonsenso is leading efforts to secure funding for a large-scale clinical trial that will test multiple treatments for long Covid in children. This trial would explore not only gut-related treatments but also anticoagulants to reduce blood vessel inflammation and medications specifically targeting conditions like postural tachycardia syndrome (POTS). POTS, a condition affecting blood flow, is a known complication of long Covid in both adults and children.

The Urgency of Finding Solutions

Parents of children with long Covid are desperate for effective treatments. Many children have struggled for months, if not years, with debilitating symptoms that affect their ability to attend school, play with friends, or even carry out everyday tasks. For these families, the need for timely, evidence-based treatments is urgent.

Dr. Yonker emphasizes the importance of focusing on pediatric treatments for long Covid. While much of the research so far has focused on adults, she believes that children cannot afford to wait for trickle-down results. “I think it’s extremely important to advocate for timely treatment advances in children suffering from long Covid rather than wait for trickle-down guidance, based on what we see from trials in adults,” she says.

Conclusion

Although the research into long Covid in children is still in its early stages, the emerging focus on the gut offers a glimmer of hope. As clinical trials like Dr. Yonker’s continue, researchers are optimistic that gut-related treatments may hold the key to alleviating the suffering of children affected by long Covid. For now, families and doctors must remain patient—but hopeful—as science continues its search for answers.

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