Larazotide Safe, Effective in Children With COVID-19-Related MIS-C

Investigators from Mass General Brigham have demonstrated that oral larazotide, an investigational drug designed to treat patients with celiac disease, led to faster gastrointestinal symptom resolution, faster clearance of spike antigen, and a faster return to typical activities in children with multisystem inflammatory syndrome (MIS-C) following SARS-CoV-2 infection, according to a study published in Science Translational Medicine.^1,2

Using larazotide to repair fissures in a leaky gut could allow for the reduction of SARS-CoV-2 spike proteins in the bloodstream. | Image Credit: © atthameeni - stock.adobe.com

MIS-C Requires Novel Interventions

The results, garnered from a small, randomized, double-blind, placebo-controlled, phase 2a trial, could shed light on a novel treatment for patients with MIS-C. A disease complication with few currently available therapies and a major burden for patients impacted, MIS-C is a novel, rare hyperinflammatory syndrome that typically presents a month or more following infection with SARS-CoV-2. It can result in difficult short-term complications, including high fever, rash, diarrhea, and abdominal pain, while major complications feature severe gastrointestinal symptoms and major cardiovascular injury, such as coronary artery aneurysms or shock.^1-3

As mentioned, there are few treatment methods available for the condition. Some patients have been prescribed anti-inflammatory therapies, but there is a major risk of a disease rebound following a therapeutic course. This is because these drugs, while successfully targeting inflammation, do not amend the underlying leakage of viral SARS-CoV-2 spike proteins from the gut into the bloodstream, which causes MIS-C.¹

Contrastingly, larazotide, a synthetic 8-amino-acid peptide that works by blocking the protein zonulin, does indeed target the gut. By strengthening intestinal barriers and keeping tight junctions in the gut lining whole, larazotide lessens hyperinflammation that can occur with a leaky gut barrier. Because of its innate gut-targeting mechanism and ability to heal the gut lining that may be shedding SARS-CoV-2 spike proteins, the investigators hypothesized that larazotide could accelerate patient recovery from MIS-C.^1,4

Larazotide Shows Promise in Children With MIS-C

The investigators enrolled a population of 12 children with MIS-C, with a median age of 5.7 years. The enrollees were included during a hospitalization for acute MISC; they were treated either with adjuvant larazotide therapy or placebo 4 times daily for 3 weeks, with monitoring continuing for 24 weeks for safety. Critically, no adverse events related to larazotide were observed by the investigators.^1,2

Blood samples analyzed by the authors indicated the correlation of the SARS-CoV-2 spike protein antigen with inflammatory markers. These included interferon-γ (IFN-γ) (P = 0.004) and IL-6 (P < 0.0001). Furthermore, gastrointestinal symptoms were assessed by the Pediatric Quality of Life Inventory (PedsQL) gastrointestinal symptom score.¹

According to the authors, in patients with MIS-C treated with larazotide, there was an observed faster resolution of gastrointestinal symptoms, faster clearance of the SARS-CoV-2 spike antigen, and a quicker return to daily activities. The results could lead to a major revelation among public health providers as to a safe, effective, and already available treatment for MIS-C and possibly lead to further breakthroughs in managing long COVID, which can occur in conjunction with MIS-C.^1,2

“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, co-director of the Pulmonary Genetics Clinic at Mass General Brigham for Children, said in a news release accompanying the study results. “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.”²

Though larger, more comprehensive studies are necessary to better elucidate the possible impacts of larazotide in patients with MIS-C, the results from this study provide an intriguing hint of larazotide’s capabilities beyond celiac disease. If proven to be effective in this population, pharmacists could have a new tool at their disposal to manage MIS-C and perhaps, if shown in research to be effective, long COVID.^1,2

REFERENCES

1. Yonker LM, Kane AS, Papadakis L, et al. Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide. Sci Translat Med. 2025;17(809). doi:10.1126/scitranslmed.adu4284

2. Mass General Brigham. Clinical trial finds safe, effective treatment for children with severe post-Covid syndrome. EurekAlert!. News Release. Released July 30, 2025. Accessed August 6, 2025. https://www.eurekalert.org/news-releases/1092914

3. DiGrande S. Mortality, Adverse Medication Events, Length of Hospital Stay Rises as More Organ Systems are Impacted by MIS-C Post-COVID-19. Pharmacy Times. Published January 26, 2023. Accessed August 6, 2025. https://www.pharmacytimes.com/view/mortality-adverse-medication-events-length-of-hospital-stay-rises-as-more-organ-systems-are-impacted-by-mis-c-post-covid-19

4. Wisconsin Institute of Functional Medicine. Larazotide: The simple peptide that could transform gut health—and more. Published March 13, 2025. Accessed August 6, 2025. https://wisconsinfunctionalmed.com/larazotide-the-simple-peptide-that-could-transform-gut-health-and-more/