Trial Report Viral spike antigen clearance and augmented recovery in children with post-COVID [MIS-C] treated with larazotide, 2025, Yonker et al

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Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide

Lael M. Yonker, Abigail S. Kane, Zoe Swank, Lena Papadakis, Victoria Kenyon, Samuel Han, Rosiane Lima, Lauren B. Guthrie, Bryan Alvarez-Carcamo, Manuella Lahoud-Rahme, Duraisamy Balaguru, Ryan W. Carroll, Josephine Lok, Chadi El Saleeby, David R. Walt, Alessio Fasano

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Editor’s summary
Some children with COVID-19 present with high fever, gastrointestinal symptoms, and cardiovascular injury. This may be associated with SARS-CoV-2 proteins such as spike antigen leaking from the gut into the bloodstream, a process mediated by zonulin.

Current treatments for this illness, called multisystem inflammatory syndrome in children (MISC), target inflammation but not the underlying leakage of viral spike protein into the bloodstream.

In a randomized, double-blind, placebo-controlled trial, Yonker et al. tested whether larazotide, a zonulin antagonist, could accelerate recovery from MISC. The authors found that larazotide treatment resulted in more rapid resolution of gastrointestinal symptoms, clearance of spike protein, and return to usual activities.

This study suggests that larazotide may be a safe and effective adjuvant treatment for MISC. —Orla Smith

Abstract
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 < 0.0001), and with gastrointestinal symptoms as assessed by the PedsQL GI symptom score (P = 0.003).

Children treated with larazotide displayed faster resolution of gastrointestinal symptoms, faster clearance of spike antigen, and a faster return to usual activities.

Our findings suggest that larazotide treatment may be safe in children and may improve resolution of symptoms when used as an adjuvant therapy for MISC.

Web | Science Translational Medicine | Paywall
 
Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide

Lael M. Yonker, Abigail S. Kane, Zoe Swank, Lena Papadakis, Victoria Kenyon, Samuel Han, Rosiane Lima, Lauren B. Guthrie, Bryan Alvarez-Carcamo, Manuella Lahoud-Rahme, Duraisamy Balaguru, Ryan W. Carroll, Josephine Lok, Chadi El Saleeby, David R. Walt, Alessio Fasano

[Line breaks added]


Editor’s summary
Some children with COVID-19 present with high fever, gastrointestinal symptoms, and cardiovascular injury. This may be associated with SARS-CoV-2 proteins such as spike antigen leaking from the gut into the bloodstream, a process mediated by zonulin.

Current treatments for this illness, called multisystem inflammatory syndrome in children (MISC), target inflammation but not the underlying leakage of viral spike protein into the bloodstream.

In a randomized, double-blind, placebo-controlled trial, Yonker et al. tested whether larazotide, a zonulin antagonist, could accelerate recovery from MISC. The authors found that larazotide treatment resulted in more rapid resolution of gastrointestinal symptoms, clearance of spike protein, and return to usual activities.

This study suggests that larazotide may be a safe and effective adjuvant treatment for MISC. —Orla Smith

Abstract
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 < 0.0001), and with gastrointestinal symptoms as assessed by the PedsQL GI symptom score (P = 0.003).

Children treated with larazotide displayed faster resolution of gastrointestinal symptoms, faster clearance of spike antigen, and a faster return to usual activities.

Our findings suggest that larazotide treatment may be safe in children and may improve resolution of symptoms when used as an adjuvant therapy for MISC.

Web | Science Translational Medicine | Paywall

As someone who has had horrendous GI symptoms since covid at the end of 2020, I would be very interested to know if this bears out and also whether this drug is suitable for adults.

Edit: Oh it's for MIS-C, I didn't clock that at first I thought general LC.
 
Last edited:
Edit: Oh it's for MIS-C, I didn't clock that at first I thought general LC.
Yes it looks interesting but it seems that this is not for LC in general but for a relatively rare complication called 'Multisystem inflammatory syndrome in children (MIS-C)'

This page says:
Most children who catch the COVID-19 virus have only a mild illness. But in children with MIS-C, after infection with the COVID-19 virus, the blood vessels, digestive system, skin or eyes become swollen and irritated.

MIS-C is rare. It most often happens within 2 months after having COVID-19. The child may have had a known infection. Or a close contact may have a confirmed infection.

Most children who have MIS-C eventually get better with medical care. But some kids quickly get worse. MIS-C can cause life-threatening illness or death.
 

News Release 30-Jul-2025

Clinical trial finds safe, effective treatment for children with severe post-Covid syndrome​

Peer-Reviewed Publication
Mass General Brigham


In a small trial, Mass General Brigham researchers found a drug designed to treat Celiac disease supported a more rapid return to normal activities for patients following COVID.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can occur after a COVID-19 infection, presenting as high fevers, gastrointestinal symptoms, and life-threatening cardiac injury. A small, randomized clinical trial led by Mass General Brigham investigators found the oral drug larazotide—an experimental drug originally designed to treat Celiac disease—was both safe and effective in treating children with MIS-C. Their results are published in Science Translational Medicine.

“While our study is small, its results are powerful and have implications not only for MIS-C, but potentially for long COVID,” said lead author Lael Yonker, MD, co-director of the Cystic Fibrosis Center, Cystic Fibrosis Therapeutic Development Center, and Pulmonary Genetics Clinic at Mass General Brigham for Children. “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.”

Current MIS-C treatments are limited. Some patients receive general anti-inflammatory drugs, but many experience a rebound of symptoms after completing a course. Such drugs are not designed to target the sticky SARS-CoV-2 viral particles that may persist in the gut. Enter larazotide, an orally administered drug that does target the gut. Larazotide strengthens intestinal barriers to limit the number of materials—like SARS-CoV-2 viral particles—that exit the intestines and enter circulation.

To test larazotide’s efficacy and safety as an MIS-C treatment, researchers conducted a double-blind clinical trial with 12 children experiencing early-stage MIS-C. The study was funded in part by the National Institutes of Health. Each patient randomly received either a placebo or larazotide four times daily for 21 days, then was tracked over six months of recovery. Children who received larazotide showed faster resolution of gastrointestinal symptoms, faster clearance of SARS-CoV-2 viral particles, and more rapid return to normal activities. The findings demonstrate larazotide may be a safe and promising treatment option for children with MIS-C.



Authorship: In addition to Yonker, Mass General Brigham authors include Abigail S. Kane, Zoe Swank, Lena Papadakis, Victoria Kenyon, Samuel Han. Rosiane Lima, Lauren B. Guthrie, Bryan Alvarez-Carcamo, Manuella Lahoud-Rahme, Duraisamy Balaguru, Ryan W. Carroll, Josephine Lok, Chadi El Saleeby, David R. Walt, and Alessio Fasano.

Disclosures: Fasano is cofounder and stockholder of Alba Therapeutics and is currently Chief Science and Medical Officer at Mead Johnson Nutrition. Walt has a financial interest in Quanterix Corporation, a company that developed an ultrasensitive digital immunoassay platform; he is an inventor of the Simoa technology, a founder of the company and also serves on its board of directors. Yonker, Walt, and Fasano are coinventors on a patent no. PCT/IB2022/052764 entitled “Zonulin antagonists for the treatment of multisystem inflammatory syndrome in children (MIS-C) and adults (MIS-A)”.


Journal​

Science Translational Medicine

DOI​

10.1126/scitranslmed.adu4284

Method of Research​

Randomized controlled/clinical trial

Subject of Research​

People

Article Title​

Clinical Trial Finds Safe, Effective Treatment for Children with Severe Post-Covid Syndrome

Article Publication Date​

30-Jul-2025

 
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