While olfactory dysfunction associated with coronavirus disease 2019 (COVID-19) has attracted considerable interest, few studies have tracked outcomes at serial time points or beyond 2 weeks. Furthermore, data are conflicting regarding whether COVID-19 severity correlates with degree of olfactory dysfunction. This prospective case-control study analyzed prevalence and severity of subjective loss of smell in outpatients (n = 23) and inpatients (n = 20) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vs healthy controls (n = 25). Olfactory dysfunction was reported more commonly in COVID-19 patients than in healthy controls ( P < .001), and outpatients paradoxically reported loss of smell more commonly than inpatients ( P = .02). Headaches were present in 52% of patients with olfactory dysfunction. Anosmia or hyposmia persisted beyond 5 days but most of the patients recovered by 30 days, suggesting favorable prognosis for olfaction. Differences between inpatients and outpatients are potentially reflective of timeline of olfactory symptoms and contextual factors, underscoring the importance of corroborative objective testing, coupled with careful tracking of temporal relationships.
Background:
Olfactory training is the only evidence-based treatment for post viral olfactory dysfunction. Smell disorders after SARS-CoV-2 infection have been attributed to neuroinflammatory events within the olfactory bulb and the central nervous system. Therefore, targeting neuroinflammation is one potential strategy for promoting recovery from post-COVID-19 chronic olfactory dysfunction. Palmitoylethanolamide and luteolin (PEA-LUT) are candidate anti-inflammatory/ neuroprotective agents.
Objective:
To investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo.
Methods:
Multicenter double-blinded randomized placebo-controlled clinical trial. Eligible subjects had prior COVID-19 and persistent olfactory impairment >6 months after follow-up SARS-CoV-2 negative testing, without prior history of olfactory dysfunction sinonasal disorders. Participants were randomized to daily oral supplementation with ultramicronized PEA-LUT 770 mg plus olfactory training (intervention group) or olfactory training with placebo (control). Sniffin’ Sticks assessments were used to test the patients at baseline and 90 days.
Results:
A total of 185 patients, including intervention (130) and control (55) were enrolled. The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls. Magnitude of recovery was significantly greater in the intervention group versus control (12.8 + 8.2 versus mean 3.2 + 3), with >10-fold higher prevalence of anosmia in control versus intervention groups at the 90-day endpoint.
Conclusion:
Among individuals with olfactory dysfunction post COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone.
(ITALIAN; Clinicaltrials.gov number: NCT04853836)
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