Publication date: Jul 30, 2025

Multisystem inflammatory syndrome (MIS) is a severe disease that occurs weeks to months after acute infection with SARS-CoV-2, often occurring in children (MISC). Symptoms include high fever, rash, nausea, diarrhea, and abdominal pain. Children with MISC can develop cardiovascular injury including ventricular failure, coronary artery aneurysms, or shock. Current treatment strategies for these postacute sequelae of COVID-19 primarily target the hyperinflammatory response. However, a potential role for viral spike protein translocated via zonulin-mediated trafficking from gastrointestinal reservoirs of SARS-CoV-2 into the circulation has been suggested. Here, we report results from a phase 2a randomized, double-blind, placebo-controlled clinical trial testing the zonulin antagonist larazotide in 12 children with MISC with a median age of 5. 7 years. Children were enrolled during hospitalization for acute MISC and were treated with adjuvant larazotide therapy four times daily for 3 weeks. Patients were monitored for 24 weeks for safety follow-up. No larazotide-related adverse events were reported. The concentration of SARS-CoV-2 spike protein antigen in blood samples correlated with inflammatory markers, including interferon-γ (IFN-γ) (P = 0. 004) and interleukin-6 (IL-6) (P

Semantics

Original Article