A multidisciplinary team from MassGeneral Hospital for Children (MGHfC), Brigham and Women’s Hospital and other institutions have identified the mechanism of how an extremely rare but severe post-COVID-19 complication develops in children and adolescents. Led by pediatric pulmonologist MGHfC, Lael Yonker, MD, the researchers determined that viral particles left in the gut long after a first COVID-19 infection can travel into the bloodstream, causing the condition called Multisystem Inflammatory Syndrome in children (MIS-C).
The syndrome can appear several weeks after the initial infection; symptoms include high fever, abdominal pain, vomiting, diarrhea, rash and extreme fatigue. The hyperinflammatory response and “cytokine storm” observed in MIS-C can cause significant damage to the heart, liver, and other organs.
Eighty percent of children hospitalized with MIS-C develop severe heart disease and face a prolonged hospital stay and an extensive recovery period. Current treatment strategies include a long-term aggressive course of steroids and intravenous immunoglobulin.
MIS-C occurs in less than 1 percent of children with confirmed SARS-CoV-2 infection. 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 strongly differentiated toward Latino and black children, with a total of 63 percent in cases of race or ethnicity.
In his recent study published in the Journal of Clinical Research, which included 100 children (19 with MIS-C, 26 with COVID-19, and 55 healthy controls), the researchers provided information on the mechanics of MIS-C and identified possible biomarkers for the early detection, treatment, and prevention of disease. They also describe the success of treating a 17-month-old baby with MIS-C.
“When we realized that 95% of children with MIS-C had SARS-CoV-2 viral particles in their feces, but with low or low levels of particles in the nose or throat, we investigated further and found that viral material that persisted in the gut long after the first COVID-19 infection could cause MIS-C “says Yonker, lead author of The team hypothesized that SARS-CoV-2 viral particles found in children’s gastrointestinal tract move into the bloodstream, leading to the characteristic hyperinflammatory immune response of MIS- C. “This is the first study to show viral particles in the blood. of MIS-C coinciding with the hyperinflammatory response, ”says Yonker.
Co-senior author Alessio Fasano, MD, head of MGHfC’s Division of Gastroenterology and Pediatric Nutrition, is an expert in the mechanics of intestinal immune responses to pathogens. 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 narrow joints between epithelial cells in the small intestine.
This opening of the spaces between epithelial cells allows the passage of substances from the intestinal lumen into the bloodstream, including gluten, which can cause symptoms in people genetically predisposed to celiac disease. In the early 2000s, Fasano developed larazotide acetate to work as a zonulin blocker in the treatment of celiac disease.
Prior to the advent of COVID-19, Fasano and Moshe Arditi, MD, director of the Cedars-Sinai Infectious and Immune Disease Research Center in Los Angeles, co-authored an article on a study of Kawasaki, a condition very similar to MIS-C, in which they showed that mice with high zonulin levels could be successfully treated with larazotide acetate. Subsequently, Arditi, Yonker, and Fasano demonstrated that the immune response to MIS-C is consistent with superantigenic activation. “The high-end protein (the superantigen) basically adheres to a T cell and causes it to trigger a continuous immune response,” Yonker says.
In the current study, researchers measured high levels of SARS-CoV-2 virus in feces and high levels of zonulin in the blood of children with MIS-C. When viral particles were later found in the blood, Fasano suggested the use of larazotide acetate as a therapeutic. Encouraging preliminary data on the efficacy of larazotide acetate in the treatment of the first case of MIS-C, after obtaining permission for compassionate use from the Food and Drug Administration, opened the possible use of larazotide acetate as the first oral treatment for COVID-19 and its complications.
“Our hypothesis was that larazotide would reduce hyperinflammation by closing tight junctions and preventing large SARS-CoV-2 virus peak proteins from entering the bloodstream,” says Fasano.
Adds Yonker: “Our next plan is to develop a clinical trial to study the effect of larazotide on the clinical outcomes of MIS-C. Going from characterizing a new disease, understanding its cause, and identifying a possible new treatment is simply amazing.” . ”
Lael M. Yonker et al, Multisystem inflammatory syndrome in children is driven by the loss of the zonulin-dependent intestinal mucosa barrier, Journal of Clinical Research (2021). DOI: 10.1172 / JCI149633
Massachusetts General Hospital
Citation: Researchers discovered mechanisms related to severe post-COVID-19 disease in children (2021, May 25) recovered on May 26, 2021 at https://medicalxpress.com/news/2021-05-uncover-mechanism -severe-post-covid- disease.html
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