Evidence map›Paper›PMID 36676175›Full record

ArticleLife (Basel, Switzerland)2023

Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?

Arianna Di Stadio, Evanthia Bernitsas, Ignazio La Mantia, Michael J Brenner, Massimo Ralli, Luigi Angelo Vaira, Andrea Colizza, Carlo Cavaliere, Matteo Laudani, Teresa C Frohman and 3 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Life (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06020937 (Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06020937 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Olfactory and Trigeminal Functions in Patients With Multiple Sclerosis

Typeobservational_patient_registrySponsorUniversity of CataniaRan2026 to 2028Enrolled200ConditionsMultiple SclerosisArmsTDI, Trigeminal Test, Cognitive Evaluation by Montreal Cognitive Assessment, Anxiety and Depression questionnaire, Visual Analogue Scale Ratings
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.Frontiers in cellular and infection microbiology · 2025
    Review
  3. Article
  4. Treatments for Olfactory Dysfunction in COVID-19: A Systematic Review.International archives of otorhinolaryngology · 2024
    Review
  5. Review
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 2 countries.

Arianna Di StadioGF Ingrassia Department, Otolaryngology, University of Catania, 95124 Catania, Italy.ORCID 0000-0001-5510-3814
Evanthia BernitsasMultiple Sclerosis Center, Neurology Department, Wayne State University, Detroit, MI 48202, USA.ORCID 0000-0001-9382-1008
Ignazio La MantiaGF Ingrassia Department, Otolaryngology, University of Catania, 95124 Catania, Italy.
Michael J BrennerOtolaryngology Department, Michigan University, Ann Arbor, MI 48109, USA.ORCID 0000-0003-4926-0957
Massimo RalliDepartment of Sense Organs, La Sapienza University, 00185 Rome, Italy.ORCID 0000-0001-8776-0421
Luigi Angelo VairaOro-Maxillo-Facial Department, University of Sassari, 07100 Sassari, Italy.ORCID 0000-0002-7789-145X
Andrea ColizzaDepartment of Sense Organs, La Sapienza University, 00185 Rome, Italy.ORCID 0000-0002-0639-806X
Carlo CavaliereDepartment of Sense Organs, La Sapienza University, 00185 Rome, Italy.
Matteo LaudaniDepartment of Neurology, University La Sapienza, 00185 Rome, Italy.
Teresa C FrohmanDistinguished Senior Fellows (Sabbatical), Laboratory of Neuroimmunology of Professor Lawrence Steinman, Stanford University School of Medicine, Stanford, CA 94305, USA.
Marco De VincentiisDepartment of Sense Organs, La Sapienza University, 00185 Rome, Italy.
Elliot M FrohmanDistinguished Senior Fellows (Sabbatical), Laboratory of Neuroimmunology of Professor Lawrence Steinman, Stanford University School of Medicine, Stanford, CA 94305, USA.
Marta AltieriDepartment of Neurology, University La Sapienza, 00185 Rome, Italy.ORCID 0000-0003-3110-5932
Sapienza University of Rome · ITStanford University · USUniversity of Catania · ITUniversity of Michigan · USUniversity of Sassari · ITWayne State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin' Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.

Indexed as

anosmiaCOVID-19disease-modifying therapyhyposmiainterferonlong COVIDlong-haul COVIDmultiple sclerosisneuroinflammationolfactionolfactoryolfactory trainingPASCpost-acute sequelae of SARS-CoV-2 infectionSARS-CoV-2smellsmell disordersTDMthreshold detection identification

Identifiers

PMID36676175
PMCPMC9863729
OpenAlexW4315864789

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.