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This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin\u2009+\u2009olfactory training (OT) (<jats:italic>umPEALUT group<\/jats:italic>, n\u2009=\u200917), (2) alpha-lipoic acid\u2009+\u2009OT (<jats:italic>ALA group<\/jats:italic>, n\u2009=\u200921), (3) umPEALUT\u2009+\u2009ALA\u2009+\u2009OT (<jats:italic>combination group<\/jats:italic>, n\u2009=\u200928), or 4) olfactory training (OT) alone (<jats:italic>control group<\/jats:italic>, n\u2009=\u200923). Olfactory function was assessed at baseline (T<jats:sub>0<\/jats:sub>) and 6\u00a0months (T<jats:sub>1<\/jats:sub>) using a parosmia questionnaire and Sniffin\u2019 Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The umPEALUT group had the largest improvement in TDI scores (21.8\u2009\u00b1\u20099.4 to 29.7\u2009\u00b1\u20097.5) followed by the combination group (19.6\u2009\u00b1\u20096.29 to 27.5\u2009\u00b1\u20092.7), both p\u2009&lt;\u20090.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p\u2009&lt;\u20090.001). Rates of parosmia resolution after 6\u00a0months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p\u2009&lt;\u20090.001). All treatment regimens were well-tolerated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00405-024-08548-6","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T08:01:56Z","timestamp":1710576116000},"page":"3671-3678","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics"],"prefix":"10.1007","volume":"281","author":[{"given":"Elena","family":"Cantone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"D\u2019Ascanio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Roccamatisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio","family":"La La Mantia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-3814","authenticated-orcid":false,"given":"Arianna","family":"Di Stadio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,16]]},"reference":[{"key":"8548_CR1","doi-asserted-by":"publisher","first-page":"bjab046","DOI":"10.1093\/chemse\/bjab046","volume":"46","author":"R Pellegrino","year":"2021","unstructured":"Pellegrino R, Mainland JD, Kelly CE, Parker JK, Hummel T (2021) Prevalence and correlates of parosmia and phantosmia among smell disorders. 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