{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:26:40Z","timestamp":1788935200089,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated to different groups based on the presence (\u201cpreviously treated\u201d) or absence (\u201cna\u00efve\u201d) of prior exposure to olfactory training. Patients were then randomized to receive PEA-LUT alone or in combination with olfactory training. Olfactory function and memory were assessed at monthly intervals using self-report measures and quantitative thresholds. A total of 69 patients (43 women, 26 men) with an age average of 40.6 + 10.5 were recruited. PEA-LUT therapy was associated with a significant improvement in validated odor identification scores at the baseline versus each subsequent month; assessment at 3 months showed an average improvement of 10.7 + 2.6, CI 95%: 6\u201314 (p &lt; 0.0001). The overall prevalence of parosmia was 79.7% (55 patients), with a significant improvement from the baseline to 3 months (p &lt; 0.0001), namely in 31 patients from the Na\u00efve 1 group (72%), 15 from the Na\u00efve 2 group (93.7%), and 9 from the remaining group (90%). Overall, mental clouding was detected in 37.7% (26 subjects) of the cases, with a reduction in severity from the baseline to three months (p = 0.02), namely in 15 patients from the Na\u00efve 1 group (34.8%), 7 from the Na\u00efve 2 group (43.7%), and 4 from the remaining group (40%). Conclusions. In patients with long COVID and chronic olfactory loss, a regimen including oral PEA-LUT and olfactory training ameliorated olfactory dysfunction and memory. Further investigations are necessary to discern biomarkers, mechanisms, and long-term outcomes.<\/jats:p>","DOI":"10.3390\/cells11162552","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T03:15:27Z","timestamp":1660706127000},"page":"2552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6505-1680","authenticated-orcid":false,"given":"Pietro","family":"De Luca","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081 Salerno, Italy"},{"name":"Otolaryngology Department, San Giovanni-Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Camaioni","sequence":"additional","affiliation":[{"name":"Otolaryngology Department, San Giovanni-Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3491-8069","authenticated-orcid":false,"given":"Pasquale","family":"Marra","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, 84081 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3947-8733","authenticated-orcid":false,"given":"Giovanni","family":"Salzano","sequence":"additional","affiliation":[{"name":"ENT and Maxillofacial Surgery Unit, Istituto Tumori G. Pascale of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Carriere","sequence":"additional","affiliation":[{"name":"Otolaryngology, Ars Medica, 00100 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5110-8386","authenticated-orcid":false,"given":"Luca","family":"Ricciardi","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Sant\u2019Andrea Hospital, Department of Neuroscience, Mental Health and Sense Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6237-2334","authenticated-orcid":false,"given":"Resi","family":"Pucci","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial, San Camillo Hospital, 00152 Rome, Italy"},{"name":"Department of Oral and Maxillofacial Science, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3686-8907","authenticated-orcid":false,"given":"Nicola","family":"Montemurro","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Pisana University Hospital, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4926-0957","authenticated-orcid":false,"given":"Michael J.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-3814","authenticated-orcid":false,"given":"Arianna","family":"Di Stadio","sequence":"additional","affiliation":[{"name":"Department of GF Ingrassia, Via di Santa Sofia 87, University of Catania, 95123 Catania, Italy"},{"name":"Neuroinflammation Lab, UCL Queen Square Neurology, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"993","DOI":"10.15585\/mmwr.mm6930e1","article-title":"CDC COVID-19 Response Team. 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