Celiac Disease Therapy Provides Benefit for Children With GI Conditions After COVID-19

Larazotide, an oral drug originally developed for celiac disease, may be a safe and effective adjunct treatment for children diagnosed with multisystem inflammatory syndrome (MIS-C)—a rare, severe condition linked to SARS-CoV-2 infection—according to findings from a phase 2a clinical trial conducted at Mass General Brigham.¹

Multisystem inflammatory syndrome in children is a rare but serious condition that affects fewer than 1% of children after COVID-19, typically appearing 2 to 6 weeks post infection. | Image credit: Gargonia - stock.adobe.com

MIS-C typically presents several weeks after acute COVID-19 infection, often with high fever, gastrointestinal (GI) symptoms, and potentially life-threatening cardiac inflammation. Standard treatments include corticosteroids, intravenous immunoglobulin (IVIG), and immunomodulators such as anakinra. However, these interventions do not always resolve symptoms fully or prevent relapses, underscoring the need for new therapeutic options.

Larazotide works by tightening the gut epithelial barrier, reducing the leakage of microbial or viral components—such as SARS-CoV-2 spike protein—into the bloodstream. Researchers hypothesized that this mechanism could mitigate the systemic inflammation seen in MIS-C, especially given mounting evidence that persistent viral antigen in the gut plays a role in the syndrome’s pathogenesis.

The study, funded in part by the National Institutes of Health, was a single-center, phase 2a, randomized, double-blind, placebo-controlled clinical trial conducted between October 2021 and June 2023. Due to a decline in MIS-C incidence following widespread COVID-19 vaccination and the emergence of new SARS-CoV-2 variants, only 12 pediatric patients were ultimately enrolled. Eligible participants ranged in age from 1 month to 21 years and met the 2021 CDC definition for MIS-C, with recent or active SARS-CoV-2 infection confirmed by polymerase chain reaction, antigen, or serologic testing. All participants exhibited systemic inflammation (C-reactive protein ≥ 3.0 mg/dL) and required hospitalization.

Following informed consent and baseline assessments, patients were randomized in blocks of 4 to receive either larazotide or placebo, administered orally 4 times daily over 21 days. Dosing was weight-based: 0.25 mg for patients under 25 kg and 0.5 mg for those 25 kg or more. Standard treatments—including steroids, IVIG, or anakinra—were continued for all participants. Follow-up included outpatient visits and telehealth assessments at days 28, 56, 84, 112, 140, and 168 to monitor adverse events, symptom progression, and biomarker changes.

The results indicated that children receiving larazotide experienced faster resolution of GI symptoms, more rapid clearance of spike protein antigen from circulation, and earlier return to baseline functioning compared with those who received placebo. Investigators observed no significant difference in adverse events between groups, affirming the drug’s safety in this population.

“While our study is small, its results are powerful and have implications not only for MIS-C, but potentially for long COVID,” Lael Yonker, MD, lead investigator and co-director of the Cystic Fibrosis Center, Cystic Fibrosis Therapeutic Development Center, and Pulmonary Genetics Clinic at Mass General Brigham for Children, emphasized.³ “Our findings suggest that larazotide is safe and quickly resolves symptoms in children with MIS-C. We are now running a clinical trial to test whether larazotide may also be a useful therapy to treat patients with long COVID.”

The researchers also found that circulating levels of spike protein correlated with GI symptoms, reinforcing their hypothesis that gut viral reservoirs contribute to systemic inflammation in MIS-C.¹ Larazotide appeared to accelerate the clearance of these viral antigens, which may explain the observed clinical improvements.

Although this trial did not evaluate larazotide in the context of long COVID or postacute sequelae of SARS-CoV-2 infection, the investigators noted symptom overlap between MIS-C and long COVID—such as fatigue and neurological complaints—and are pursuing further research to examine larazotide’s efficacy in broader post-viral inflammatory syndromes.

References

1. Yonker LM, Kane AS, Swank Z, et al. Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide. Sci Transl Med. Published online July 30, 2025. doi:10.1126/scitranslmed.adu4284

2. Clinical trial finds safe, effective treatment for children with severe post-Covid syndrome. News release. Mass General Brigham. July 30, 2025. Accessed July 30, 2025. https://www.eurekalert.org/news-releases/1092914