In part one of this blog, we discuss how odor changes can occur after COVID-19. We also presented two studies that examined the (preventive) effect of saline and corticosteroid nasal sprays.
In this blog, we summarize the results of four studies that examine the benefits of various pharmacological interventions for odor disorders. The table below shows a brief overview of the results of all six studies.
- Gabapentin for Post-COVID Olfactory Dysfunction
Gabapentin is commonly used to treat neuropathic pain. In the GRACE randomized clinical trial Gabapentin was recently explored as a potential treatment for COVID-induced olfactory dysfunction.
In this double-blinded, placebo-controlled trial 68 patients with olfactory dysfunction persisting for at least three months after SARS-CoV-2 infection were included. Patients were randomized to receive either gabapentin or placebo.
The primary outcome was subjective improvement in smell, as measured by the Clinical Global Impression of Improvement (CGI-I). Unfortunately, the results showed no significant difference between the gabapentin and placebo groups. Although some patients in both groups reported slight improvements, gabapentin did not provide any clinically meaningful or statistically significant benefit.
Despite its theoretical neuro-regenerative properties, the findings suggest that gabapentin is not an effective treatment for COVID-19–related olfactory dysfunction. This trial underscores the need for continued research into more efficacious therapies.
- Intranasal EDTA: Chelation Therapy for Olfactory Recovery
In another approach, a study explored the use of ethylene diamine tetra acetic acid (EDTA), a calcium-chelating agent, as a nasal spray to treat post-COVID olfactory dysfunction. Calcium ions play a role in the desensitization of olfactory receptor neurons, and by binding to these ions, EDTA could theoretically restore olfactory function.
This randomized trial involved 50 patients divided into two groups: one received standard olfactory training, while the other received olfactory training combined with a 1% EDTA nasal spray.
Results showed that 88% of patients in the EDTA group experienced clinical improvement in their sense of smell. Only 60% of patients in the olfactory training-only group experienced clinical improvement of their sense of smell. Additionally, the EDTA group demonstrated a significant reduction in nasal calcium levels, further supporting the hypothesis that chelation therapy could mitigate the calcium-induced desensitization of ORNs.
These findings suggest that intranasal EDTA could be a valuable addition for treatment of COVID-19-induced olfactory dysfunction. However, further research with larger sample sizes is necessary to confirm these results.
- Palmitoylethanolamide and Alpha-Lipoic Acid for Persistent COVID-19 Parosmia
A study explored the effectiveness of combining ultramicronized palmitoylethanolamide and luteolin (umPEALUT) with alpha-lipoic acid (ALA) for treating persistent COVID-19 parosmia.
In this randomized clinical trial, 85 patients were divided into four groups: umPEALUT + olfactory training (OT), ALA + OT, both umPEALUT and ALA + OT, or OT alone (control group).
The changes in olfactory function were assessed by a Sniffin' Sticks test of odor threshold, detection, and identification (TDI). The umPEALUT group achieved the most significant improvements in olfactory function with TDI scores rising from 21.8 to 29.7 after six months. The second highest improvement was observed in the combination group which received all treatment combined (19.6 to 27.5).
In contrast, the ALA and control groups saw minimal or no improvement. Additionally, parosmia resolution rates were highest in the combination group (96%) and lowest in the ALA group (29%), highlighting the potential of umPEALUT as an effective treatment for chronic olfactory impairment.
- Platelet-Rich Plasma for Post-COVID Olfactory Dysfunction
Another study explored the use of platelet-rich plasma (PRP) as a treatment for olfactory dysfunction. In a randomized controlled trial involving 83 patients, platelet-rich plasma was applied topically in the olfactory clefts of patients with persistent olfactory dysfunction post-COVID-19.
Patients treated with platelet-rich plasma experienced a statistically significant increase in odor identification scores (BSIT) between months 5 and 9, compared to placebo. While total scores for odor detection did not differ significantly between groups, the platelet-rich plasma group demonstrated modest improvements in olfactory function over time.
While validation of these results in a larger group of patients is still necessary, platelet-rich plasma could be considered as a potential therapy for patients with long-term smell loss following COVID-19.
The variety of treatments for olfactory dysfunction is expanding, yet more research is needed.
Olfactory dysfunction is a debilitating consequence of COVID-19 for many patients. Current research, ranging from intranasal chelation therapies like EDTA to olfactory training and pharmacological interventions, provide hope for those suffering from persistent smell loss.
However, much work remains to be done to establish clear, effective treatments for COVID-19-induced olfactory dysfunction. As more studies are conducted and new therapies are developed, it is essential for patients to consult with healthcare providers about the latest treatment options.
If you are experiencing changes in smell and taste yourself, check out our guidebook on olfactory training or discuss your experiences in the Altea Forum.
