Randomized clinical trial "olfactory dysfunction after COVID-19: olfactory rehabilitation therapy vs. intervention treatment with Palmitoylethanolamide and Luteolin": preliminary results

Eur Rev Med Pharmacol Sci. 2021 Jun;25(11):4156-4162. doi: 10.26355/eurrev_202106_26059.


Objective: Approximately 30% of patients with confirmed COVID-19 report persistent smell or taste disorders as long-term sequalae of infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory changes to the olfactory bulb, and treatments with anti-inflammatory properties are hypothesized to attenuate viral injury and promote recovery of olfaction after infection. Our study investigated the efficacy of a supplement with Palmitoylethanolamide (PEA) and Luteolin to support recovery of olfaction in COVID-19 patients.

Patients and methods: We conducted a randomized-controlled pilot study in outpatients with history of confirmed COVID-19 with post-infection olfactory impairment that persisted ≥ 90 days after SARS-CoV-2 negative testing. Patients were randomized to two times a day olfactory rehabilitation alone or weekly olfactory rehabilitation plus daily oral supplement with PEA and Luteolin. Subjects with preexisting olfactory disorders were excluded. Sniffin' Sticks assessments were performed at baseline and 30 days after treatment. Data on gender, age, and time since infection were collected. Kruskal-Wallis (KW) test was used to compare variances of Sniff scores between groups over time, and Spearman's correlation coefficients were calculated to assess for correlations between Sniff Score and gender or duration of infection.

Results: Among 12 patients enrolled (n=7, supplement; n=5, controls), patients receiving supplement had greater improvement in olfactory threshold, discrimination, and identification score versus controls (p=0.01). Time since infection was negatively correlated with Sniff Score, and there was no correlation between gender.

Conclusions: Treatment combining olfactory rehabilitation with oral supplementation with PEA and Luteolin was associated with improved recovery of olfactory function, most marked in those patients with longstanding olfactory dysfunction. Further studies are necessary to replicate these findings and to determine whether early intervention including olfactory rehabilitation and PEA+Luteolin oral supplement might prevent SARS-CoV-2 associated olfactory impairment.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amides / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Antiviral Agents / administration & dosage*
  • COVID-19 / complications
  • COVID-19 / diagnosis
  • COVID-19 Drug Treatment*
  • Drug Therapy, Combination
  • Ethanolamines / administration & dosage*
  • Female
  • Humans
  • Luteolin / administration & dosage*
  • Male
  • Middle Aged
  • Olfaction Disorders / diagnosis
  • Olfaction Disorders / drug therapy*
  • Olfaction Disorders / etiology
  • Palmitic Acids / administration & dosage*
  • Pilot Projects
  • Single-Blind Method
  • Smell / drug effects
  • Smell / physiology


  • Amides
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antiviral Agents
  • Ethanolamines
  • Palmitic Acids
  • palmidrol
  • Luteolin