COVID-19 Risks: MIS-C and Under-Vaccination

Bernice D. Mowery, PhD, RN


Pediatr Nurs. 2021;47(6):303-304. 

In This Article

MIS-C is Driven by Zonulin-dependent Loss of gut Mucosal Barrier

Multisystem inflammatory syndrome in children (MIS-C) occurs weeks after children have been exposed to SARS-CoV-2, the virus causing COVID-19. Usually, the virus cannot be cultured from the respiratory tract of children with MIS-C respiratory tract, so the cause of MIS-C is undetermined. Standard treatment, steroids, and immunoglobulin therapy (IVIG) target the inflammatory response but not the cause. Measures to identify MIS-C etiology and develop a treatment for MIS-C early before cardiac complications occur are needed.

Yonker and colleagues (2021) investigated 100 children, 19 with MIS-C, 26 with COVID-19, and 55 controls. Significantly more children with MIS-C had gastrointestinal symptoms (GI) (89%) than children with COVID-19 (27%), as well as significantly higher levels of SARS-CoV-2 in stool samples. The authors hypothesized that prolonged presence of SARS-CoV-2 in the GI tract leads to release of zonulin, a protein biomarker of intestinal permeability, with consequent trafficking of SARS-CoV-2 into the blood-stream, resulting in antigenemia and hyperinflammation. Increased circulating zonulin has also been noted in inflammatory diseases, including celiac and Kawasaki diseases. The authors included informative illustrations that make it easy to follow research steps and rationale for their hypothesis.

To further confirm the role of zonulin in MIS-C, the authors administered a zonulin antagonist, larazotide (clinical III trials for Celiac disease), to a critically ill 17-month-old failing to respond with standard therapy, reducing spike antigenemia, cytokine storm, and improving clinical status. Further research with larger samples is needed to confirm pathogenesis and to explore the prevention and treatment of MIS-C.