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Scientists have identified a promising drug candidate for the treatment of a rare but severe, and potentially life-threatening condition in children infected with the SARS-CoV-2 virus, that causes Covid-19.
Multi-inflammatory syndrome in children (MIS-C) usually develops weeks to months after children have experienced a mild or even asymptomatic case of Covid-19, the researchers said.MIS-C leads to high fevers and a hyperinflammatory response that can affect multiple organs, including the heart, brain and gastrointestinal organs, they said.
A previous study by researchers at Massachusetts General Hospital (MGH) and Brigham and Women's Hospital (BWH) in the US showed that in cases of MIS-C, the SARS-CoV-2 virus can remain in the gut for weeks to months after the infection.
When SARS-CoV-2 is present in the gut, an impaired mucosal barrier can allow small viral particles, such as the spike protein, to enter the bloodstream, leading to infections such as Covid-19 and in rare cases, the hyperinflammatory response that triggers MIS-C.
The SARS-CoV-2 virus uses the spike protein to enter and infect the cells.
"Working collaboratively, we have been able to demonstrate that viral particles that remain in the gut long after Covid-19 infection can instigate MIS-C," said David Walt, senior author of the study published in the journal Critical Care Explorations."Building on this important discovery, we wanted to see if treatment with a drug developed for another condition -- celiac disease -- could help resolve symptoms in children experiencing MIS-C," said Walt.
The team administered the drug larazotide acetate to four extremely ill children ages 3 to 17 being treated for MIS-C.
The study shows that larazotide decreases the release of zonulin, a molecule that can lead to increased gut permeability and an impaired mucosal barrier, a layer of thick mucus in the gut.
The researchers compared the clinical outcomes of the four children who received larazotide plus steroids and intravenous immune globulin (IVIG) to 22 children who received only steroids and IVIG.The children who received four daily oral doses of larazotide acetate had a significantly faster resolution of gastrointestinal symptoms and a slightly shorter hospital stay, they said.The study also found that serum levels of the spike protein dropped much more quickly in children treated with larazotide, clearing from the blood within one day, versus 10 days for children not treated with the drug."These findings suggest that larazotide may provide a safe and beneficial adjuvant therapy for the treatment of MIS-C," the researchers said."Expansion of clinical trials is urgently needed to ascertain the clinical impact of larazotide on MIS-C," they added.
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