{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T12:27:02Z","timestamp":1769257622990,"version":"3.49.0"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"809","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,7,30]]},"abstract":"<jats:p>\n            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-\u03b3 (IFN-\u03b3) (\n            <jats:italic toggle=\"yes\">P<\/jats:italic>\n            \u00a0=\u00a00.004) and interleukin-6 (IL-6) (\n            <jats:italic toggle=\"yes\">P<\/jats:italic>\n            \u00a0&lt;\u00a00.0001), and with gastrointestinal symptoms as assessed by the PedsQL GI symptom score (\n            <jats:italic toggle=\"yes\">P<\/jats:italic>\n            \u00a0=\u00a00.003). 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.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adu4284","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T17:58:26Z","timestamp":1753898306000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1711-8227","authenticated-orcid":true,"given":"Lael M.","family":"Yonker","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Harvard Medical School, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-6151","authenticated-orcid":true,"given":"Abigail S.","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8825-0335","authenticated-orcid":true,"given":"Zoe","family":"Swank","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA."},{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Papadakis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Kenyon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4695-2720","authenticated-orcid":true,"given":"Samuel","family":"Han","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA."},{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosiane","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren B.","family":"Guthrie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0174-5860","authenticated-orcid":true,"given":"Bryan","family":"Alvarez-Carcamo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3580-9945","authenticated-orcid":true,"given":"Manuella","family":"Lahoud-Rahme","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Harvard Medical School, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4790-7879","authenticated-orcid":true,"given":"Duraisamy","family":"Balaguru","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Harvard Medical School, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-7023","authenticated-orcid":true,"given":"Ryan W.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Harvard Medical School, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8320-0961","authenticated-orcid":true,"given":"Josephine","family":"Lok","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Harvard Medical School, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chadi","family":"El Saleeby","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Harvard Medical School, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5524-7348","authenticated-orcid":true,"given":"David R.","family":"Walt","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA."},{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, MA, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-0261","authenticated-orcid":true,"given":"Alessio","family":"Fasano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, USA."},{"name":"Harvard Medical School, Boston, MA, USA."},{"name":"European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"National Institute of Allergy and Infectious Diseases \u201cLong COVID and multisystem inflammatory syndrome in children (MIS-C)\u201d; www.niaid.nih.gov\/diseases-conditions\/long-covid-multisystem-inflammatory-syndrome-children-misc."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.8823"},{"key":"e_1_3_2_4_2","unstructured":"National Notifiable Diseases Surveillance System \u201cMultisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection 2023 case definition\u201d; https:\/\/ndc.services.cdc.gov\/case-definitions\/multisystem-inflammatory-syndrome-in-children-mis-c-2023\/."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021680"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI149633"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100848"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo3627"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI146614"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07722-4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI151520"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.2091"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.41616"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.24369"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2024.09.001"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac722"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00386.2020"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867328666210104110053"},{"key":"e_1_3_2_19_2","first-page":"e0641","article-title":"Zonulin antagonist, larazotide (AT1001), as an adjuvant treatment for multisystem inflammatory syndrome in children: A case series","volume":"10","author":"Yonker L. M.","year":"2022","unstructured":"L. M. Yonker, Z. Swank, T. Gilboa, Y. Senussi, V. Kenyon, L. Papadakis, B. P. Boribong, R. W. Carroll, D. R. Walt, A. Fasano, Zonulin antagonist, larazotide (AT1001), as an adjuvant treatment for multisystem inflammatory syndrome in children: A case series. Crit. Care Explor. 10, e0641 (2022).","journal-title":"Crit. 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