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; Marco De Vincentiis; Elliot M. Frohman; Marta Altieri

doi:10.3390/life13010226

Life (Jan 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,
Marco De Vincentiis,
Elliot M. Frohman,
Marta Altieri

Affiliations

Arianna Di Stadio: GF Ingrassia Department, Otolaryngology, University of Catania, 95124 Catania, Italy
Evanthia Bernitsas: Multiple Sclerosis Center, Neurology Department, Wayne State University, Detroit, MI 48202, USA
Ignazio La Mantia: GF Ingrassia Department, Otolaryngology, University of Catania, 95124 Catania, Italy
Michael J. Brenner: Otolaryngology Department, Michigan University, Ann Arbor, MI 48109, USA
Massimo Ralli: Department of Sense Organs, La Sapienza University, 00185 Rome, Italy
Luigi Angelo Vaira: Oro-Maxillo-Facial Department, University of Sassari, 07100 Sassari, Italy
Andrea Colizza: Department of Sense Organs, La Sapienza University, 00185 Rome, Italy
Carlo Cavaliere: Department of Sense Organs, La Sapienza University, 00185 Rome, Italy
Matteo Laudani: Department of Neurology, University La Sapienza, 00185 Rome, Italy
Teresa C. Frohman: Distinguished Senior Fellows (Sabbatical), Laboratory of Neuroimmunology of Professor Lawrence Steinman, Stanford University School of Medicine, Stanford, CA 94305, USA
Marco De Vincentiis: Department of Sense Organs, La Sapienza University, 00185 Rome, Italy
Elliot M. Frohman: Distinguished Senior Fellows (Sabbatical), Laboratory of Neuroimmunology of Professor Lawrence Steinman, Stanford University School of Medicine, Stanford, CA 94305, USA
Marta Altieri: Department of Neurology, University La Sapienza, 00185 Rome, Italy

DOI: https://doi.org/10.3390/life13010226
Journal volume & issue: Vol. 13, no. 1
p. 226

Abstract

Read online

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.

Published in Life

ISSN: 2075-1729 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science
Website: http://www.mdpi.com/journal/life

About the journal

Abstract

Keywords