{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:34:52Z","timestamp":1777646092535,"version":"3.51.4"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004505","name":"Universit\u00e0 degli Studi di Catania","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004505","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Arch Otorhinolaryngol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Few evidence-based therapies are available for chronic olfactory dysfunction after COVID-19. This study investigated the relative efficacy of olfactory training alone, co-ultramicronized palmitoylethanolamide with luteolin (um-PEA\u2013LUT, an anti-neuroinflammatory supplement) alone, or combined therapy for treating chronic olfactory dysfunction from COVID-19.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This double-blinded controlled, placebo-controlled multicenter randomized clinical trial was conducted in 202 patients with persistent COVID-19 olfactory dysfunction of\u2009&gt;\u20096\u00a0month duration. After a screening nasal endoscopy, patients were randomized to: (1) olfactory training and placebo; (2) once daily um-PEA\u2013LUT alone; (3) twice daily um-PEA\u2013LUT alone; or (4) combination of once daily um-PEA\u2013LUT with olfactory training. Olfactory testing (Sniffin\u2019 Sticks odor identification test) was performed at baseline and at 1, 2, and 3\u00a0months. The primary outcome was recovery of over three points on olfactory testing, with outcomes compared at <jats:italic>T<\/jats:italic><jats:sub>0<\/jats:sub>, <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub>, <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> and <jats:italic>T<\/jats:italic><jats:sub>3<\/jats:sub> across groups. Statistical analyses included one-way ANOVA for numeric data and chi-square for nominal data.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>All patients completed the study, and there were no adverse events. At 90 days, odor identification scores improved by\u2009&gt;\u20093 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA\u2013LUT alone, and 41.6% receiving once daily um-PEA\u2013LUT alone (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.00001). Patients receiving treatment with um-PEA\u2013LUT alone demonstrated subclinical improvement (&lt;\u20093 point odor identification improvement) more often than patients receiving olfactory training with placebo (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001.)<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Olfactory training plus once daily um-PEA\u2013LUT resulted in greater olfactory recovery than either therapy alone in patients with long-term olfactory function due to COVID-19.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>20112020PGFN on clinicaltrials.gov.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Level of evidence<\/jats:title>\n                <jats:p>1b (Individual Randomized Clinical Trial).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00405-023-08085-8","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T16:02:26Z","timestamp":1687968146000},"page":"4949-4961","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial"],"prefix":"10.1007","volume":"280","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-3814","authenticated-orcid":false,"given":"Arianna","family":"Di Stadio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Gallina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Cocuzza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"De Luca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Ingrassia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Oliva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Sireci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Camaioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Ferreli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Mercante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Gaino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gian Marco","family":"Pace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignazio","family":"La Mantia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"issue":"8","key":"8085_CR1","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1001\/jamaoto.2020.1155","volume":"146","author":"G Mercante","year":"2020","unstructured":"Mercante G, Ferreli F, De Virgilio A, Gaino F, Di Bari M, Colombo G, Russo E, Costantino A, Pirola F, Cugini G, Malvezzi L, Morenghi E, Azzolini E, Lagioia M, Spriano G (2020) Prevalence of taste and smell dysfunction in coronavirus disease 2019. JAMA Otolaryngol Head Neck Surg 146(8):723\u2013728","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"5","key":"8085_CR2","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1007\/s00415-020-10135-8","volume":"268","author":"A Cocco","year":"2021","unstructured":"Cocco A, Amami P, Desai A, Voza A, Ferreli F, Albanese A (2021) Neurological features in SARS-CoV-2-infected patients with smell and taste disorder. J Neurol 268(5):1570\u20131572","journal-title":"J Neurol"},{"issue":"8","key":"8085_CR3","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1002\/alr.22990","volume":"12","author":"F Ferreli","year":"2022","unstructured":"Ferreli F, Gaino F, Russo E, Di Bari M, Rossi V, De Virgilio A, Di Stadio A, Spriano G, Mercante G (2022) Long-term olfactory dysfunction in COVID-19 patients: 18-month follow-up study. Int Forum Allergy Rhinol 12(8):1078\u20131080","journal-title":"Int Forum Allergy Rhinol"},{"issue":"9","key":"8085_CR4","doi-asserted-by":"publisher","first-page":"4633","DOI":"10.1007\/s00405-022-07428-1","volume":"279","author":"F Ferreli","year":"2022","unstructured":"Ferreli F, Gaino F, Russo E, Di Bari M, Rossi V, De Virgilio A, Malvezzi L, Colombo G, Cristalli G, Spriano G, Mercante G (2022) Long-standing gustatory and olfactory dysfunction in COVID-19 patients: a prospective study. Eur Arch Otorhinolaryngol 279(9):4633\u20134640","journal-title":"Eur Arch Otorhinolaryngol"},{"issue":"9","key":"8085_CR5","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/S1474-4422(21)00182-4","volume":"20","author":"MS Xydakis","year":"2021","unstructured":"Xydakis MS, Albers MW, Holbrook EH, Lyon DM, Shih RY, Frasnelli JA, Pagenstecher A, Kupke A, Enquist LW, Perlman S (2021) Post-viral effects of COVID-19 in the olfactory system and their implications. Lancet Neurol 20(9):753\u2013761. https:\/\/doi.org\/10.1016\/S1474-4422(21)00182-4","journal-title":"Lancet Neurol"},{"issue":"1","key":"8085_CR6","first-page":"1","volume":"26","author":"A Di Stadio","year":"2022","unstructured":"Di Stadio A, D\u2019Ascanio L, La Mantia I, Ralli M, Brenner MJ (2022) Parosmia after COVID-19: olfactory training, neuroinflammation and distortions of smell. Eur Rev Med Pharmacol Sci 26(1):1\u20133","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"8085_CR7","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.clnesp.2021.03.021","volume":"43","author":"NJ Wierdsma","year":"2021","unstructured":"Wierdsma NJ, Kruizenga HM, Konings LA, Krebbers D, Jorissen JR, Joosten MI, van Aken LH, Tan FM, van Bodegraven AA, Soeters MR, Weijs PJ (2021) Poor nutritional status, risk of sarcopenia and nutrition related complaints are prevalent in COVID-19 patients during and after hospital admission. Clin Nutr ESPEN 43:369\u2013376. https:\/\/doi.org\/10.1016\/j.clnesp.2021.03.021","journal-title":"Clin Nutr ESPEN"},{"issue":"10266","key":"8085_CR8","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1016\/S0140-6736(20)32662-3","volume":"396","author":"T Lancet","year":"2020","unstructured":"Lancet T (2020) Facing up to long COVID. Lancet 396(10266):1861","journal-title":"Lancet"},{"issue":"2","key":"8085_CR9","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s00408-021-00423-z","volume":"199","author":"DL Sykes","year":"2021","unstructured":"Sykes DL, Holdsworth L, Jawad N, Gunasekera P, Morice AH, Crooks MG (2021) Post-COVID-19 symptom burden: what is long-COVID and how should we manage it? Lung 199(2):113\u2013119","journal-title":"Lung"},{"key":"8085_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174582","volume":"912","author":"E Khani","year":"2021","unstructured":"Khani E, Khiali S, Beheshtirouy S, Entezari-Maleki T (2021) Potential pharmacologic treatments for COVID-19 smell and taste loss: a comprehensive review. Eur J Pharmacol 912:174582","journal-title":"Eur J Pharmacol"},{"issue":"9","key":"8085_CR11","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1080\/13543784.2022.2113054","volume":"31","author":"A Di Stadio","year":"2022","unstructured":"Di Stadio A, Severini C, Colizza A, De Vincentiis M, La Mantia I (2022) Investigational drugs for the treatment of olfactory dysfunction. Expert Opin Investig Drugs 31(9):945\u2013955","journal-title":"Expert Opin Investig Drugs"},{"issue":"3","key":"8085_CR12","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1002\/lary.20101","volume":"119","author":"T Hummel","year":"2009","unstructured":"Hummel T, Rissom K, Reden J, H\u00e4hner A, Weidenbecher M, H\u00fcttenbrink KB (2009) Effects of olfactory training in patients with olfactory loss. Laryngoscope 119(3):496\u2013499","journal-title":"Laryngoscope"},{"issue":"10","key":"8085_CR13","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.2174\/1570159X20666220420113513","volume":"20","author":"A Di Stadio","year":"2022","unstructured":"Di Stadio A, D\u2019Ascanio L, Vaira LA, Cantone E, De Luca P, Cingolani C, Motta G, De Riu G, Vitelli F, Spriano G, De Vincentiis M, Camaioni A, La Mantia I, Ferreli F, Brenner MJ (2022) Ultramicronized palmitoylethanolamide and luteolin supplement combined with olfactory training to treat post-COVID-19 olfactory impairment: a multi-center double-blinded randomized placebo- controlled clinical trial. Curr Neuropharmacol 20(10):2001\u20132012","journal-title":"Curr Neuropharmacol"},{"issue":"16","key":"8085_CR14","doi-asserted-by":"publisher","first-page":"2552","DOI":"10.3390\/cells11162552","volume":"11","author":"P De Luca","year":"2022","unstructured":"De Luca P, Camaioni A, Marra P, Salzano G, Carriere G, Ricciardi L, Pucci R, Montemurro N, Brenner MJ, Di Stadio A (2022) Effect of ultra-micronized palmitoylethanolamide and luteolin on olfaction and memory in patients with long COVID: results of a longitudinal study. Cells 11(16):2552","journal-title":"Cells"},{"issue":"7","key":"8085_CR15","first-page":"3440","volume":"24","author":"M Ralli","year":"2020","unstructured":"Ralli M, Di Stadio A, Greco A, de Vincentiis M, Polimeni A (2020) Defining the burden of olfactory dysfunction in COVID-19 patients. Eur Rev Med Pharmacol Sci 24(7):3440\u20133441","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"5","key":"8085_CR16","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S2213-2600(21)00125-9","volume":"9","author":"WJ Song","year":"2021","unstructured":"Song WJ, Hui CKM, Hull JH, Birring SS, McGarvey L, Mazzone SB, Chung KF (2021) Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses. Lancet Respir Med 9(5):533\u2013544","journal-title":"Lancet Respir Med"},{"key":"8085_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.840121","volume":"16","author":"ME Tremblay","year":"2022","unstructured":"Tremblay ME, Madore C, Tian L, Verkhratsky A (2022) Editorial: role of neuroinflammation in the neuropsychiatric and neurological aspects of COVID-19. Front Cell Neurosci 16:840121","journal-title":"Front Cell Neurosci"},{"issue":"7","key":"8085_CR18","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1002\/lary.30101","volume":"132","author":"A Altundag","year":"2022","unstructured":"Altundag A, Yilmaz E, Kesimli MC (2022) Modified olfactory training is an effective treatment method for COVID-19 induced parosmia. Laryngoscope 132(7):1433\u20131438","journal-title":"Laryngoscope"},{"issue":"11","key":"8085_CR19","first-page":"4156","volume":"25","author":"L D\u2019Ascanio","year":"2021","unstructured":"D\u2019Ascanio L, Vitelli F, Cingolani C, Maranzano M, Brenner MJ, Di Stadio A (2021) Randomized clinical trial \u201colfactory dysfunction after COVID-19: olfactory rehabilitation therapy vs intervention treatment with Palmitoylethanolamide and Luteolin\u201d: preliminary results. Eur Rev Med Pharmacol Sci 25(11):4156\u20134162","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"8","key":"8085_CR20","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1002\/sim.4447","volume":"31","author":"OM Kuznetsova","year":"2012","unstructured":"Kuznetsova OM, Tymofyeyev Y (2012) Preserving the allocation ratio at every allocation with biased coin randomization and minimization in studies with unequal allocation. Stat Med 31(8):701\u2013723","journal-title":"Stat Med"},{"issue":"2","key":"8085_CR21","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/S0197-2456(98)00056-7","volume":"20","author":"CR Palmer","year":"1999","unstructured":"Palmer CR, Rosenberger WF (1999) Ethics and practice: alternative designs for phase III randomized clinical trials. Control Clin Trials 20(2):172\u2013186","journal-title":"Control Clin Trials"},{"issue":"1","key":"8085_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cct.2005.08.003","volume":"27","author":"JC Dumville","year":"2006","unstructured":"Dumville JC, Hahn S, Miles JN, Torgerson DJ (2006) The use of unequal randomisation ratios in clinical trials: a review. Contemp Clin Trials 27(1):1\u201312","journal-title":"Contemp Clin Trials"},{"issue":"2","key":"8085_CR23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1177\/135581969700200205","volume":"2","author":"D Torgerson","year":"1997","unstructured":"Torgerson D, Campbell M (1997) Unequal randomisation can improve the economic efficiency of clinical trials. J Health Serv Res Policy 2(2):81\u201385","journal-title":"J Health Serv Res Policy"},{"issue":"Pt A","key":"8085_CR24","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.cct.2015.05.017","volume":"45","author":"E Peckham","year":"2015","unstructured":"Peckham E, Brabyn S, Cook L, Devlin T, Dumville J, Torgerson DJ (2015) The use of unequal randomisation in clinical trials\u2014an update. Contemp Clin Trials 45(Pt A):113\u2013122","journal-title":"Contemp Clin Trials"},{"issue":"10","key":"8085_CR25","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.jclinepi.2014.05.015","volume":"67","author":"C Dibao-Dina","year":"2014","unstructured":"Dibao-Dina C, Caille A, Sautenet B, Chazelle E, Giraudeau B (2014) Rationale for unequal randomization in clinical trials is rarely reported: a systematic review. J Clin Epidemiol 67(10):1070\u20131075","journal-title":"J Clin Epidemiol"},{"issue":"1S","key":"8085_CR26","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.1016\/j.chest.2020.03.010","volume":"158","author":"X Wang","year":"2020","unstructured":"Wang X, Ji X (2020) Sample size estimation in clinical research: from randomized controlled trials to observational studies. Chest 158(1S):S12\u2013S20","journal-title":"Chest"},{"issue":"3","key":"8085_CR27","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1007\/s00405-018-5248-1","volume":"276","author":"A Oleszkiewicz","year":"2019","unstructured":"Oleszkiewicz A et al (2019) Updated Sniffin\u2019 sticks normative data based on an extended sample of 9139 subjects. Eur Arch Otorhinolaryngol 276(3):719\u2013728","journal-title":"Eur Arch Otorhinolaryngol"},{"issue":"1","key":"8085_CR28","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/chemse\/22.1.39","volume":"22","author":"T Hummel","year":"1997","unstructured":"Hummel T et al (1997) \u2018Sniffin\u2019 Sticks\u2019: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Sens 22(1):39\u201352","journal-title":"Chem Sens"},{"issue":"3","key":"8085_CR29","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s00405-006-0173-0","volume":"264","author":"T Hummel","year":"2007","unstructured":"Hummel T, Kobal G, Gudziol H, Mackay-Sim A (2007) Normative data for the \u201cSniffin\u2019 Sticks\u201d including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3000 subjects. Eur Arch Otorhinolaryngol 264(3):237\u2013243","journal-title":"Eur Arch Otorhinolaryngol"},{"issue":"9","key":"8085_CR30","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1001\/jamaoto.2022.1573","volume":"148","author":"S Gupta","year":"2022","unstructured":"Gupta S, Lee JJ, Perrin A, Khan A, Smith HJ, Farrell N, Kallogjeri D, Piccirillo JF (2022) Efficacy and safety of saline nasal irrigation plus theophylline for treatment of COVID-19-related olfactory dysfunction: the SCENT2 phase 2 randomized clinical trial. JAMA Otolaryngol Head Neck Surg 148(9):830\u2013837","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"9","key":"8085_CR31","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1001\/jamaoto.2022.1574","volume":"148","author":"JJ Lee","year":"2022","unstructured":"Lee JJ, Gupta S, Kallogjeri D, Piccirillo JF (2022) Safety of high-dose nasal theophylline irrigation in the treatment of postviral olfactory dysfunction: a dose-escalation study. JAMA Otolaryngol Head Neck Surg 148(9):885\u2013886","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"8","key":"8085_CR32","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1001\/jamaoto.2020.1378","volume":"146","author":"JM Levy","year":"2020","unstructured":"Levy JM (2020) Treatment recommendations for persistent smell and taste dysfunction following COVID-19-the coming Deluge. JAMA Otolaryngol Head Neck Surg 146(8):733","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"1","key":"8085_CR33","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1001\/jamaoto.2021.3379","volume":"148","author":"AM Khan","year":"2021","unstructured":"Khan AM, Kallogjeri D, Piccirillo JF (2021) Growing public health concern of COVID-19 chronic olfactory dysfunction. JAMA Otolaryngol Head Neck Surg 148(1):81\u201382","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"key":"8085_CR34","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD013876.pub3","author":"L O'Byrne","year":"2022","unstructured":"O\u2019Byrne L, Webster KE, MacKeith S, Philpott C, Hopkins C, Burton MJ (2022) Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction. Cochrane Database Syst Rev. https:\/\/doi.org\/10.1002\/14651858.CD013876.pub3","journal-title":"Cochrane Database Syst Rev"},{"issue":"18","key":"8085_CR35","doi-asserted-by":"publisher","first-page":"185","DOI":"10.2147\/TCRM.S354695","volume":"5","author":"B Hu","year":"2022","unstructured":"Hu B, Zhang J, Gong M, Deng Y, Cao Y, Xiang Y, Ye D (2022) Research progress of olfactory nerve regeneration mechanism and olfactory training. Ther Clin Risk Manag 5(18):185\u2013195","journal-title":"Ther Clin Risk Manag"},{"issue":"Pt A","key":"8085_CR36","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.brainres.2016.07.014","volume":"1648","author":"E Parrella","year":"2016","unstructured":"Parrella E, Porrini V, Iorio R, Benarese M, Lanzillotta A, Mota M, Fusco M, Tonin P, Spano P, Pizzi M (2016) PEA and luteolin synergistically reduce mast cell-mediated toxicity and elicit neuroprotection in cell-based models of brain ischemia. Brain Res 1648(Pt A):409\u2013417","journal-title":"Brain Res"},{"key":"8085_CR37","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.mito.2018.09.003","volume":"46","author":"A Di Stadio","year":"2019","unstructured":"Di Stadio A, Angelini C (2019) Microglia polarization by mitochondrial metabolism modulation: a therapeutic opportunity in neurodegenerative diseases. Mitochondrion 46:334\u2013336","journal-title":"Mitochondrion"},{"issue":"4","key":"8085_CR38","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1111\/bph.13139","volume":"173","author":"R Orihuela","year":"2016","unstructured":"Orihuela R, McPherson CA, Harry GJ (2016) Microglial M1\/M2 polarization and metabolic states. Br J Pharmacol 173(4):649\u2013665","journal-title":"Br J Pharmacol"},{"issue":"11","key":"8085_CR39","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/S1474-4422(20)30308-2","volume":"19","author":"J Matschke","year":"2020","unstructured":"Matschke J, L\u00fctgehetmann M, Hagel C, Sperhake JP, Schr\u00f6der AS, Edler C, Mushumba H, Fitzek A, Allweiss L, Dandri M, Dottermusch M, Heinemann A, Pfefferle S, Schwabenland M, Sumner Magruder D, Bonn S, Prinz M, Gerloff C, P\u00fcschel K, Krasemann S, Aepfelbacher M, Glatzel M (2020) Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol 19(11):919\u2013929","journal-title":"Lancet Neurol"},{"issue":"9","key":"8085_CR40","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.3390\/antiox10091448","volume":"10","author":"YJ Ahn","year":"2021","unstructured":"Ahn YJ, Kim H (2021) Lutein as a modulator of oxidative stress-mediated inflammatory diseases. Antioxidants (Basel) 10(9):1448","journal-title":"Antioxidants (Basel)"},{"issue":"6","key":"8085_CR41","doi-asserted-by":"publisher","first-page":"3054","DOI":"10.3390\/ijms22063054","volume":"22","author":"A D'Aloia","year":"2021","unstructured":"D\u2019Aloia A, Molteni L, Gullo F, Bresciani E, Artusa V, Rizzi L, Ceriani M, Meanti R, Lecchi M, Coco S, Costa B, Torsello A (2021) Palmitoylethanolamide modulation of microglia activation: characterization of mechanisms of action and implication for its neuroprotective effects. Int J Mol Sci 22(6):3054","journal-title":"Int J Mol Sci"},{"issue":"4","key":"8085_CR42","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S1474-4422(21)00059-4","volume":"20","author":"The Lancet Neurology","year":"2021","unstructured":"The Lancet Neurology (2021) Long COVID: understanding the neurological effects. Lancet Neurol 20(4):247","journal-title":"Lancet Neurol"},{"issue":"10312","key":"8085_CR43","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1016\/S0140-6736(21)02143-7","volume":"398","author":"COVID-19 Mental Disorders Collaborators","year":"2021","unstructured":"COVID-19 Mental Disorders Collaborators (2021) Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet 398(10312):1700\u20131712","journal-title":"Lancet"},{"issue":"2","key":"8085_CR44","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3390\/brainsci12020154","volume":"12","author":"A Di Stadio","year":"2022","unstructured":"Di Stadio A, Brenner MJ, De Luca P, Albanese M, D\u2019Ascanio L, Ralli M, Roccamatisi D, Cingolani C, Vitelli F, Camaioni A, Di Girolamo S, Bernitsas E (2022) Olfactory dysfunction, headache, and mental clouding in adults with long-COVID-19: what is the link between cognition and olfaction? A cross-sectional study. Brain Sci 12(2):154","journal-title":"Brain Sci"},{"key":"8085_CR45","doi-asserted-by":"publisher","unstructured":"Global Burden of Disease Long COVID Collaborators, Wulf Hanson S, Abbafati C, Aerts JG, Al-Aly Z, Ashbaugh C, Ballouz T, Blyuss O, Bobkova P, Bonsel G, Borzakova S, Buonsenso D, Butnaru D, Carter A, Chu H, De Rose C, Diab MM, Ekbom E, El Tantawi M, Fomin V, Frithiof R, Gamirova A, Glybochko PV, Haagsma JA, Haghjooy Javanmard S, Hamilton EB, Harris G, Heijenbrok-Kal MH, Helbok R, Hellemons ME, Hillus D, Huijts SM, Hultstr\u00f6m M, Jassat W, Kurth F, Larsson IM, Lipcsey M, Liu C, Loflin CD, Malinovschi A, Mao W, Mazankova L, McCulloch D, Menges D, Mohammadifard N, Munblit D, Nekliudov NA, Ogbuoji O, Osmanov IM, Pe\u00f1alvo JL, Petersen MS, Puhan MA, Rahman M, Rass V, Reinig N, Ribbers GM, Ricchiuto A, Rubertsson S, Samitova E, Sarrafzadegan N, Shikhaleva A, Simpson KE, Sinatti D, Soriano JB, Spiridonova E, Steinbeis F, Svistunov AA, Valentini P, van de Water BJ, van den Berg-Emons R, Wallin E, Witzenrath M, Wu Y, Xu H, Zoller T, Adolph C, Albright J, Amlag JO, Aravkin AY, Bang-Jensen BL, Bisignano C, Castellano R, Castro E, Chakrabarti S, Collins JK, Dai X, Daoud F, Dapper C, Deen A, Duncan BB, Erickson M, Ewald SB, Ferrari AJ, Flaxman AD, Fullman N, Gamkrelidze A, Giles JR, Guo G, Hay SI, He J, Helak M, Hulland EN, Kereselidze M, Krohn KJ, Lazzar-Atwood A, Lindstrom A, Lozano R, Malta DC, M\u00e5nsson J, Mantilla Herrera AM, Mokdad AH, Monasta L, Nomura S, Pasovic M, Pigott DM, Reiner RC Jr, Reinke G, Ribeiro ALP, Santomauro DF, Sholokhov A, Spurlock EE, Walcott R, Walker A, Wiysonge CS, Zheng P, Bettger JP, Murray CJL, Vos T (2022) Estimated global proportions of individuals with persistent fatigue, cognitive, and respiratory symptom clusters following symptomatic COVID-19 in 2020 and 2021. JAMA. https:\/\/doi.org\/10.1001\/jama.2022.18931","DOI":"10.1001\/jama.2022.18931"},{"issue":"1","key":"8085_CR46","doi-asserted-by":"publisher","first-page":"17","DOI":"10.4193\/Rhino16.195","volume":"55","author":"A Sorokowska","year":"2017","unstructured":"Sorokowska A, Drechsler E, Karwowski M, Hummel T (2017) Effects of olfactory training: a meta-analysis. Rhinology 55(1):17\u201326","journal-title":"Rhinology"}],"container-title":["European Archives of Oto-Rhino-Laryngology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00405-023-08085-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00405-023-08085-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00405-023-08085-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T15:03:17Z","timestamp":1696863797000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00405-023-08085-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,28]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["8085"],"URL":"https:\/\/doi.org\/10.1007\/s00405-023-08085-8","relation":{},"ISSN":["0937-4477","1434-4726"],"issn-type":[{"value":"0937-4477","type":"print"},{"value":"1434-4726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,28]]},"assertion":[{"value":"30 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no disclosures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}