Discussion
infection, olfactory loss, olfactory disorders, smell loss, smell disorders, parosmia
OLFACTORY DISORDER, DISORDERS, INFECTION, SMELL DISORDERS, PAROSMIA
This study is the first trial assessing the effect of alpha-lipoic acid as an adjuvant of olfactory training on the improvement of smell loss in post-COVID-19 patients.Herein, we found a strong statistically significant differences in CCCRC olfactory scores and VAS in the follow-up period in both groups. Comparing the mean scores of smell tests, both groups have improved CCCRC score (In 2002, Hummel et al. concluded that alpha-lipoic acid (ALA) might be helpful in patients with olfactory loss after upper respiratory tract.Alpha-lipoic acid is a fatty acid that penetrates the blood–brain barrier. It is metabolized into cell to its active metabolite, Dihydro-Lipoic Acid (DHLA).Regarding SARS-CoV-2’s physiopathology of the infection, it is important to remember that SARS-CoV adheres its Spike protein (S) to the host cell membrane through the Angiotensin-Converting Enzyme 2 (ACE-2) receptor.In the specific case of the olfactory neuroepithelium, ACE-2 has a higher expression in the supporting, basal and perivascular cells than in the olfactory neurons themselves. So, the olfactory disorders in post-COVID-19 tend to be primarily due to non-neural cellular changes.According to the British Rhinology Society Loss of Smell Consensus,Olfactory training has been known to have a beneficial effect on the olfactory sense. The exposure to odors results in an increased growth of olfactory receptor neurons and an increased expression of olfactory receptors.In despite we found a negative results to alpha-lipoic acid as an adjuvant in smell loss recover due to COVID-19, our results support the safety of olfactory training. This is a simple and relatively low-cost therapy that should be done by ENT or a general practitioner physician.This study has some limitations. Firstly, when we started this study, there were not any trial published about olfactory training or alpha-lipoic acid as a treatment to improve smell loss after COVID-19. So, sample size calculation was difficult. Thereat, we over expected a great size effect in alpha-lipoic acid use. Although this impacted on our study, the results confirmed the positive effect of OT for this condition.Besides that, once traditional medical training overvalues drug intervention, complementary therapies cannot be forgotten. Also, our study did not have a control group where spontaneous recovery only was observed. We found an ethical issue in leaving part of participants without any promising treatment.Finally, we did not assess the effects of alpha-acid lipoic and olfactory training in qualitative disorders, like parosmia. We planned to do that in another study. Furthermore, we plan to follow up these patients for 6–12 months after clinical onset to observe longer effects of treatment.To our knowledge, the present study is the first double-blind, randomized trials to evaluate alpha lipoic acid as an adjuvant treatment for long-lasting severe olfactory disorders in COVID-19 patients. Given the high incidence of this infection in the population, there are significant and increasing numbers of patients with persistent smell disorders needing treatment.