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Published May 25, 2021
https://doi.org/10.1172/JCI149633
Lael M. Yonker,1 Tal Gilboa,2 Alana F. Ogata,2 Yasmeen Senussi,2 Roey Lazarovits,2Brittany P. Boribong,1 Yannic C. Bartsch,3 Maggie Loiselle,1 Magali Noval Rivas,4 Rebecca A. Porritt,4 Rosiane Lima,1 Jameson P. Davis,1 Eva J. Farkas,1 Madeleine D. Burns,1 Nicola Young,1 Vinay S. Mahajan,3 Soroush Hajizadeh,5 Xcanda I. Herrera Lopez,5 Johannes Kreuzer,5 Robert Morris,5 Enid E. Martinez,1 Isaac Han,6 Kettner Griswold Jr.,6 Nicholas C. Barry,6 David B. Thompson,6 George Church,7 Andrea G. Edlow,8 Wilhelm Haas,5 Shiv Pillai,9 Moshe Arditi,4 Galit Alter,10 David R. Walt,11 and Alessio Fasano1
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.
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https://doi.org/10.1172/JCI149633
Lael M. Yonker,1 Tal Gilboa,2 Alana F. Ogata,2 Yasmeen Senussi,2 Roey Lazarovits,2Brittany P. Boribong,1 Yannic C. Bartsch,3 Maggie Loiselle,1 Magali Noval Rivas,4 Rebecca A. Porritt,4 Rosiane Lima,1 Jameson P. Davis,1 Eva J. Farkas,1 Madeleine D. Burns,1 Nicola Young,1 Vinay S. Mahajan,3 Soroush Hajizadeh,5 Xcanda I. Herrera Lopez,5 Johannes Kreuzer,5 Robert Morris,5 Enid E. Martinez,1 Isaac Han,6 Kettner Griswold Jr.,6 Nicholas C. Barry,6 David B. Thompson,6 George Church,7 Andrea G. Edlow,8 Wilhelm Haas,5 Shiv Pillai,9 Moshe Arditi,4 Galit Alter,10 David R. Walt,11 and Alessio Fasano1
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.
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