Introduction
inflammation, anosmia, infection, Neuroinflammation, post-viral smell disorders, COVID-19 olfactory impairment, olfactory dysfunction
INFLAMMATION, INFECTION, CORONAVIRUS, PATHOGENESIS, SEVERE ACUTE RESPIRATORY SYNDROME
Transient anosmia is often present in the acute phase of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and it occurs most commonly in patients with mild or moderate COVID-19 [The unmet needs of patients with long COVID and olfactory loss represent a looming public health crisis [In the pandemic era, um-PEA–LUT has been repurposed as a potential therapy of COVID-19 olfactory impairment. The PEA component of the supplement acts on microglia to promote an anti-inflammatory, neuroprotective and tissue repair profile (M2 phenotype). The LUT component reduces reactive oxygen species (ROS), and in patients with persistent olfactory loss after COVID-19, this combination therapy is thought to counteract inflammation of olfactory bulbs and neuro-epithelium. A prior randomized trial found that the combination of um-PEA–LUT and olfactory training allowed better olfactory recovery than olfactory training alone [These data provided the impetus for the present study. Neuroinflammation has been implicated in the pathogenesis of post-viral smell disorders [This double-blinded multicenter clinical trial investigated four therapeutic regimens for persistent post-COVID-19 olfactory dysfunction. It sought to determine (1) the relative efficacy of um-PEA–LUT alone, olfactory training alone, and combined therapy with um-PEA–LUT plus olfactory training (OT) for promoting olfactory recovery; (2) whether olfactory recovery differed among patients receiving once-daily vs. twice-daily administration of um-PEA–LUT alone.