Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier.
J Clin Invest
; 131(14)2021 07 15.
Article
in English
| MEDLINE | ID: covidwho-1311202
ABSTRACT
BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.METHODSHere, we analyzed biospecimens from 100 children 19 with MIS-C, 26 with acute COVID-19, and 55 controls. Stools were assessed for SARS-CoV-2 by reverse transcription PCR (RT-PCR), and plasma was examined 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 a proof of concept, we treated a patient with MIS-C with larazotide, a zonulin antagonist, and monitored the effect on antigenemia and the patient's clinical response.RESULTSWe showed that in children with MIS-C, a prolonged presence of SARS-CoV-2 in the GI tract led to the release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation. The patient with MIS-C treated with larazotide had a coinciding decrease in plasma SARS-CoV-2 spike antigen levels and inflammatory markers and a resultant clinical improvement above that achieved with currently available treatments.CONCLUSIONThese mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protein Precursors
/
Haptoglobins
/
Systemic Inflammatory Response Syndrome
/
SARS-CoV-2
/
COVID-19
/
Intestinal Mucosa
Type of study:
Observational study
/
Prognostic study
Limits:
Adolescent
/
Adult
/
Child
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Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Infant, Newborn
/
Young adult
Language:
English
Year:
2021
Document Type:
Article
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