{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:52:45Z","timestamp":1767707565125,"version":"3.41.2"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T00:00:00Z","timestamp":1697760000000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Waning immunity after vaccination justifies the need for additional effective COVID\u201019 treatments. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate mucosal immunity, which can prevent SARS\u2010CoV\u20102 main immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections using an enteral route, which point to potential effects on time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID\u201019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary<\/jats:title><jats:p>This pilot clinical trial investigated the effect of buccopharyngeal administered high polyphenolic olive oil on COVID\u201019 incidence, duration, and severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Importance<\/jats:title><jats:p>Waning immunity after vaccination justifies the need of further research for additional effective treatments for COVID\u201019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Immunomodulation of local immune response at the buccopharyngeal mucosa could hypothetically activate mucosal immunity, which would in turn difficult SARS\u2010CoV\u20102 immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections, using an enteral route, which suggest potential shortening of time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID\u201019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>Double blind, randomized pilot clinical trial conducted at a single site, Talavera de la Reina, Spain. Potential study participants were identified by simple random sampling from the epidemiological database of contact patients recently diagnosed of COVID\u201019 during the study period. A total of 88 adult participants were enrolled and 84 completed the 3\u2010month study, conducted between July 1, 2021 and August 31, 2022.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>Participants were randomized to receive oromucosal administered high polyphenolic olive oil, 2\u2009mL twice a day for 3 months or no treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome and Measures<\/jats:title><jats:p>Primary outcomes were incidence, duration, and severity of COVID\u201019 after intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no differences in incidence between both groups but there were significant differences in duration, the median time to resolution of symptoms was 3 days in the high polyphenolic olive oil group compared with 7 days in the no\u2010treatment group. Although time to resolution is directly related to severity, this study did not find any differences in severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Relevance<\/jats:title><jats:p>Among full\u2010vaccinated adults recent infected with COVID\u201019, a daily intake of tiny quantities of oromucosal administered high polyphenolic olive oil before infection significantly improved the time to symptom resolution. This finding strongly support the appropriateness of further deep research on the use of oromucosal administered high polyphenolic olive oil as an effective immune strategy against COVID\u201019.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.1054","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T07:32:04Z","timestamp":1697787124000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Buccopharyngeal route administered high polyphenolic olive oil and COVID\u201019: A pilot clinical trial"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8682-9279","authenticated-orcid":false,"given":"Francisco","family":"Rodr\u00edguez\u2010Argente","sequence":"first","affiliation":[{"name":"Hospital Universitario Nuestra Se\u00f1ora del Prado  Talavera de la Reina 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