Mechanism of Severe Post-COVID-19 Disease in Kids Revealed

Viral particles in the gut can travel into the bloodstream, causing Multisystem Inflammatory Syndrome in Children (MIS-C) in kids post-COVID. Symptoms include high fever, abdominal pain, vomiting, diarrhea, rash and extreme fatigue. The hyperinflammatory response and "cytokine storm" seen in MIS-C can lead to extensive damage in the heart, liver and other organs.

Eighty percent of children hospitalized with MIS-C develop heart issues pathology and had a prolonged hospital stay and extensive recovery period. Aggressive, long-term course of steroids and intravenous immunoglobulin should be given.

As of May 3, 2021, the U.S. Centers for Disease Control and Prevention reported 3,742 children diagnosed with MIS-C and 35 deaths. U.S. statistics are skewed heavily toward Latino and Black children, with a total of 63 percent in cases with race or ethnicity listed.

In the study published in the Journal of Clinical Investigation, which included 100 children (19 with MIS-C, 26 with COVID-19 and 55 healthy controls), the researchers provide the information on mechanics of MIS-C and identify potential biomarkers for early disease detection, treatment and prevention. They describe the successful treatment of a 17-month-old infant with MIS-C.

"When we realized that 95 percent of the children with MIS-C had SARS-CoV-2 viral particles in their stool but no or low levels of particles in their noses or throats, we investigated further and found that viral material lingering in the gut long after the first COVID-19 infection could lead to MIS-C," says Yonker, lead author of the paper.

The hypothesis is that SARS-CoV-2 viral particles found in the gastrointestinal tract of children move into the bloodstream, leading to the hyperinflammatory immune response characteristic of MIS-C. "This is the first study showing viral particles in the blood of MIS-C coinciding with the hyperinflammatory response," says Yonker.

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In 2000, Fasano and his team at the University of Maryland School of Medicine discovered zonulin, a protein that regulates intestinal permeability by opening the tight junctions between gut epithelial cells in the small intestine.

Fasano developed larazotide acetate to work as a zonulin blocker in the treatment of celiac disease.

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Prior to the advent of COVID-19, Fasano and Moshe Arditi, MD, director of the Infectious and Immunological Diseases Research Center at Cedars-Sinai in Los Angeles, co-authored a paper about a study on Kawasaki disease.

Later, Arditi, Yonker and Fasano showed that the immune response in MIS-C is consistent with superantigenic activation. "The large spike protein--the superantigen--basically holds onto a T-cell and makes it fire off a continuous immune response," says Yonker.

Researchers measured high levels of SARS-CoV-2 virus in the stools and zonulin in the blood of children with MIS-C. When they subsequently found viral particles in the blood, Fasano suggested the use of larazotide acetate as a therapeutic.

Larazotide acetate found effective in treating the first case of MIS-C, after obtaining compassionate use permission from the Food and Drug Administration, opened up the possible use of larazotide acetate as the first oral treatment for COVID-19 and its complications.

"Our hypothesis was that larazotide would reduce the hyperinflammation by closing the tight junctions and preventing the large spike proteins of the SARS-CoV-2 virus from entering the bloodstream," says Fasano.

Adds Yonker: "Our next plan is to develop a clinical trial to study the effect of larazotide on clinical outcomes in MIS-C. To go from characterizing a new disease, to understanding its cause, to identifying a possible new treatment is just incredible."



Source-Medindia