{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:49:00Z","timestamp":1790804940017,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age &gt;18 and &lt; 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia\/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and\/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms.<\/jats:p>","DOI":"10.3390\/brainsci12020154","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:44:33Z","timestamp":1643143473000},"page":"154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Arianna","family":"Di Stadio","sequence":"first","affiliation":[{"name":"Department GF Ingrassia, University of Catania, 95123 Catania, 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 48105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6505-1680","authenticated-orcid":false,"given":"Pietro","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno, 84125 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-2017","authenticated-orcid":false,"given":"Maria","family":"Albanese","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-326X","authenticated-orcid":false,"given":"Luca","family":"D\u2019Ascanio","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, AORMN, 61032 Fano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8776-0421","authenticated-orcid":false,"given":"Massimo","family":"Ralli","sequence":"additional","affiliation":[{"name":"Organ of Sense Department, University La Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Roccamatisi","sequence":"additional","affiliation":[{"name":"Psychology Department, UTIU, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Cingolani","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, AORMN, 61032 Fano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Vitelli","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, AORMN, 61032 Fano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Camaioni","sequence":"additional","affiliation":[{"name":"Otolaryngology Department, San Giovanni Addolorata Hospital, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Di Girolamo","sequence":"additional","affiliation":[{"name":"Unit of Otorhinolaryngology, Department of Clinical Sciences and Translation Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-1008","authenticated-orcid":false,"given":"Evanthia","family":"Bernitsas","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Neurology Department, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707207","DOI":"10.3389\/fneur.2021.707207","article-title":"Auditory Disturbances and SARS-CoV-2 Infection: Brain Inflammation or Cochlear Affection? 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