Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier

[Mary Wilson]

Published May 25, 2021

https://doi.org/10.1172/JCI149633

Lael M. Yonker,[SUP]1[/SUP] Tal Gilboa,[SUP]2[/SUP] Alana F. Ogata,[SUP]2[/SUP] Yasmeen Senussi,[SUP]2[/SUP] Roey Lazarovits,[SUP]2[/SUP]Brittany P. Boribong,[SUP]1[/SUP] Yannic C. Bartsch,[SUP]3[/SUP] Maggie Loiselle,[SUP]1[/SUP] Magali Noval Rivas,[SUP]4[/SUP] Rebecca A. Porritt,[SUP]4[/SUP] Rosiane Lima,[SUP]1[/SUP] Jameson P. Davis,[SUP]1[/SUP] Eva J. Farkas,[SUP]1[/SUP] Madeleine D. Burns,[SUP]1[/SUP] Nicola Young,[SUP]1[/SUP] Vinay S. Mahajan,[SUP]3[/SUP] Soroush Hajizadeh,[SUP]5[/SUP] Xcanda I. Herrera Lopez,[SUP]5[/SUP] Johannes Kreuzer,[SUP]5[/SUP] Robert Morris,[SUP]5[/SUP] Enid E. Martinez,[SUP]1[/SUP] Isaac Han,[SUP]6[/SUP] Kettner Griswold Jr.,[SUP]6[/SUP] Nicholas C. Barry,[SUP]6[/SUP] David B. Thompson,[SUP]6[/SUP] George Church,[SUP]7[/SUP] Andrea G. Edlow,[SUP]8[/SUP] Wilhelm Haas,[SUP]5[/SUP] Shiv Pillai,[SUP]9[/SUP] Moshe Arditi,[SUP]4[/SUP] Galit Alter,[SUP]10[/SUP] David R. Walt,[SUP]11[/SUP] and Alessio Fasano[SUP]1[/SUP]

Background: Weeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called Multisystem Inflammatory Syndrome in Children (MIS-C). Gastrointestinal symptoms are common in MIS-C patients and severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not previously been identified.

Methods: Here, we analyzed biospecimens from 100 children: 19 children with MIS-C, 26 with acute COVID-19, and 55 controls. Stool was assessed for SARS-CoV-2 by RT-PCR and plasma was assessed for markers of breakdown of mucosal barrier integrity, including zonulin. Ultrasensitive antigen detection was used to probe for SARS-CoV-2 antigenemia in plasma, and immune responses were characterized. As proof of concept, we treated a MIS-C patient with larazotide, a zonulin antagonist, and monitored impact on antigenemia and clinical response.
...
https://www.jci.org/articles/view/149633

 

[Mary Wilson]

Study shows how rare but serious post-COVID-19 complication develops in children, adolescents

Reviewed by Emily Henderson, B.Sc. May 26 2021

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 serious post-COVID-19 complication develops in children and adolescents.

Led by MGHfC pediatric pulmonologist Lael Yonker, MD, researchers determined that viral particles remaining in the gut long after an initial COVID-19 infection can travel into the bloodstream, instigating the condition called Multisystem Inflammatory Syndrome in Children (MIS-C).

The syndrome can occur several weeks after an initial infection; 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 severe cardiac pathology and face a prolonged hospital stay and extensive recovery period. Current treatment strategies include an aggressive, long-term course of steroids and intravenous immunoglobulin. ...

https://www.news-medical.net/news/2...ication-develops-in-children-adolescents.aspx