Researchers identify potential factor in rare but serious post-COVID-19 illness in children

A young girl wearing a mask is examined by a physician who is also wearing a mask.

A team of NIH–funded researchers discovered a pathway that may explain why some children and adolescents develop a very rare, but serious post-COVID-19 condition known as multisystem inflammatory syndrome in children (MIS-C). Hallmark features include a fever accompanied by other symptoms, such as stomach pain, chest tightness, headache, or fatigue. Some children may also experience gastrointestinal symptoms, like vomiting or diarrhea.  
After collecting blood and stool samples from 100 children who had MIS-C, COVID-19, or who served as controls, researchers found children with MIS-C had higher levels of multiple inflammatory markers in their bloodstream. This signaled their body was still responding to COVID-19. These children also had traces of the coronavirus in their stool and higher levels of zonulin, a protein associated with a leaky gut. These findings, along with the presence of the biomarker soluble CD14, suggested the coronavirus moved from cells lining a child’s gut into their bloodstream. Since zonulin is elevated in children with celiac disease and signals a similar process with gluten entering the bloodstream, the researchers wanted to see if blocking zonulin would improve MIS-C symptoms.  

After receiving compassionate use approval from the Food and Drug Administration, the researchers gave larazotide, a zonulin inhibitor that’s being tested for celiac disease, to an infant with severe MIS-C. The baby’s fever fell, he started feeding again, and his gastrointestinal symptoms improved. Inflammatory markers associated with COVID-19 also decreased. The researchers will now start a clinical trial to see if this therapeutic approach may help other children with MIS-C.  The study published in The Journal of Clinical Investigation and was supported by the NHLBI, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Diseases.