Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics

Eur Arch Otorhinolaryngol. 2024 Jul;281(7):3671-3678. doi: 10.1007/s00405-024-08548-6. Epub 2024 Mar 16.

Abstract

Purpose: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment.

Methods: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin' 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.

Results: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. 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 < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated.

Conclusions: 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.

Keywords: Alpha lipoic acid; Anosmia; Coronavirus long-COVID; Palmitoylethanolamide; Parosmia.

Publication types

  • Randomized Controlled Trial
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Amides / therapeutic use
  • Anosmia / etiology
  • Anosmia / therapy
  • COVID-19* / complications
  • Combined Modality Therapy
  • Ethanolamines / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Olfaction Disorders* / etiology
  • Olfaction Disorders* / rehabilitation
  • Olfaction Disorders* / therapy
  • Olfactory Training
  • Palmitic Acids / administration & dosage
  • Palmitic Acids / therapeutic use
  • SARS-CoV-2
  • Smell / physiology
  • Thioctic Acid* / administration & dosage
  • Thioctic Acid* / therapeutic use
  • Treatment Outcome

Substances

  • Thioctic Acid
  • Ethanolamines
  • Palmitic Acids
  • Amides
  • palmidrol