{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T06:32:04Z","timestamp":1770100324259,"version":"3.49.0"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Maxima Medical Center Innovation Fund","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether oral treatment with 12.5\u2009mg iodine additional to standard of care is effective in reducing mortality and clinical deterioration of patients hospitalized with COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a single center, randomized clinical trial (EudraCT 2020-001852-16) in which patients with severe covid-19 in need of hospitalization were randomized in two groups. The first group received 12.5\u2009mg oral iodine for 8 days, the second group did not receive iodine next to the standard of care. Primary endpoints were deterioration of disease defined as transfer from the ward to the intensive care unit (ICU) or death. Next to these parameters we collected parameters in line with the recommendations made by the WHO in the early days of the pandemic. On these additional datasets we performed an exploratory analysis and investigated possible confounders and trends. The inclusion phase of the study was between October 2020 and April 2022. Finally,\n                      <jats:italic>in vitro<\/jats:italic>\n                      validations were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Outcomes from 141 participants were analyzed, revealing no significant differences in mortality or transfers to intensive care between the iodine-treated group (67 patients) and the control group (74 patients). In an exploratory analysis we found that patients randomized to receive oral iodine had a significantly shorter stay at the ICU (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016).\n                      <jats:italic>In vitro<\/jats:italic>\n                      validations proved increased virus-induced type I interferon responses upon iodine administration in pulmonary cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that while iodine does not reduce mortality or ICU admissions, it may enhance antiviral immunity through increased type I interferon responses, contributing to shorter ICU stays in COVID-19 patients. The role of iodine in enhancing IFN-I mediated antiviral immunity warrants future research.<\/jats:p>\n                    <jats:p>\n                      Registration of trial: EudraCT Number: 2020-001852-16.\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/search?query=2020-001852-16\" xlink:type=\"simple\">https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/search?query=2020-001852-16<\/jats:ext-link>\n                    <\/jats:p>\n                    <jats:p>\n                      Sponsor name: Maxima Medical Center. Date of Registration: April 1\n                      <jats:sup>st<\/jats:sup>\n                      2020.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0341126","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:23:23Z","timestamp":1770056603000},"page":"e0341126","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Iodine increases pulmonary type I interferon responses and decreases covid-19 disease severity: Results from an open label randomized clinical trial"],"prefix":"10.1371","volume":"21","author":[{"given":"Ren\u00e9","family":"Traksel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-3157","authenticated-orcid":true,"given":"Jasper","family":"Broen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjen","family":"van Henten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"K\u00f6nigs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arjun","family":"Raj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7230-1134","authenticated-orcid":true,"given":"Laura","family":"van Eyndhoven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Verheesen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"issue":"9","key":"pone.0341126.ref001","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.3390\/nu16091345","article-title":"The efficacy of multivitamin, Vitamin A, Vitamin B, Vitamin C, and Vitamin D supplements in the prevention and management of COVID-19 and Long-COVID: an updated systematic review and meta-analysis of randomized clinical trials","volume":"16","author":"A Sinopoli","year":"2024","journal-title":"Nutrients"},{"key":"pone.0341126.ref002","doi-asserted-by":"crossref","first-page":"109860","DOI":"10.1016\/j.mehy.2020.109860","article-title":"Iodine, a preventive and curative agent in the COVID-19 pandemic?","volume":"144","author":"RH Verheesen","year":"2020","journal-title":"Med Hypotheses"},{"key":"pone.0341126.ref003","first-page":"199","article-title":"The 1957 pandemic of influenza in India","volume":"20","author":"IG Menon","year":"1959","journal-title":"Bull World Health Organ"},{"key":"pone.0341126.ref004","article-title":"Iodine a specific germicide in respiratory affections: preliminary report","author":"S Blum","year":"1914","journal-title":"Cal State J Med"},{"issue":"19","key":"pone.0341126.ref005","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.3390\/nu14193886","article-title":"Thyroidal and extrathyroidal requirements for iodine and selenium: a combined evolutionary and (Patho) physiological approach","volume":"14","author":"DAJ Dijck-Brouwer","year":"2022","journal-title":"Nutrients"},{"issue":"1","key":"pone.0341126.ref006","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1080\/07853890.2022.2076902","article-title":"Repurposing povidone-iodine to reduce the risk of SARS-CoV-2 infection and transmission: a narrative review","volume":"54","author":"N-A Lim","year":"2022","journal-title":"Ann Med"},{"issue":"3","key":"pone.0341126.ref007","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s40121-020-00316-3","article-title":"Povidone-iodine demonstrates rapid in vitro virucidal activity against SARS-CoV-2, the virus causing COVID-19 disease","volume":"9","author":"DE Anderson","year":"2020","journal-title":"Infect Dis Ther"},{"issue":"2","key":"pone.0341126.ref008","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1165\/rcmb.2012-0529OC","article-title":"Increased concentration of iodide in airway secretions is associated with reduced respiratory syncytial virus disease severity","volume":"50","author":"RJ Derscheid","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"4","key":"pone.0341126.ref009","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/BF00186651","article-title":"In vivo and in vitro studies into the immunological changes following iodine 131 therapy for Graves\u2019 disease","volume":"18","author":"R Wilson","year":"1991","journal-title":"Eur J Nucl Med"},{"issue":"5","key":"pone.0341126.ref010","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202012481","article-title":"Why does Japan have so few cases of COVID-19?","volume":"12","author":"A Iwasaki","year":"2020","journal-title":"EMBO Mol Med"},{"key":"pone.0341126.ref011","unstructured":"World Health Organisation. 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