Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out

Abstract

Background: Anosmia is defined as the complete absence of olfactory function, which can be caused by a variety of causes, with upper respiratory tract infections being among the most frequent causes. Anosmia due to SARS-CoV-2 infection has attracted attention given its main role in symptomatology and the social impact of the pandemic. Methods: We conducted systematic research in a clinicaltrials.gov database to evaluate all active clinical trials worldwide regarding drug therapies in adult patients for anosmia following SARS-CoV-2 infection with the intention of identifying the nearby prospects to treat Anosmia. We use the following search terms: "Anosmia" AND "COVID-19" OR "SARS-CoV-2" OR "2019 novel coronavirus". Results: We found 18 active clinical trials that met our criteria: one phase 1, one phase 1-2, five phases 2, two phases 2-3, three phases 3, and six phases 4 studies were identified. The drug therapies that appear more effective and promising are PEA-LUT and Cerebrolysin. The other interesting drugs are 13-cis-retinoic acid plus aerosolized Vitamin D, dexamethasone, and corticosteroid nasal irrigation. Conclusions: COVID-19 has allowed us to highlight how much anosmia is an important and debilitating symptom for patients and, above all, to direct research to find a therapy aimed at curing the symptom, whether it derives from SARS-CoV-2 infection or other infections of the upper airways. Some of these therapies are very promising and are almost at the end of experimentation. They also provide hope in this field, which not addressed until recently.

Keywords: anosmia; clinical trials; olfactory impairment; post-COVID-19; smell; therapy.

Figure 1

Odorant signal transmission and the human olfactory system. Focus is on the olfactory system and neuroepithelium, composed of olfactory sensory neurons that, through the lamina cribrosa plate, establish a synaptic connection with the mitral and tufted cells of the olfactory bulb. The axons of the monosynaptic mitral and tufted cells that make up the olfactory tract bifurcate at the terminus, fornix, or olfactory cortices. Primarily, the limbic system with the pyriform cortex, amygdala, and entorhinal cortex is involved [4]. Olfactory impairment induces modifications to smell, as reported in the text. (Modified from medical illustration by Patrick J. Lynch).

Figure 2

23 clinical trials were identified, 5 were excluded, and 18 were retained. Phase distribution of 18 clinical trials in post-COVID-19 patients affected by anosmia was analyzed in this report.

Figure 3

Overview of administered drugs in the clinical trials.

Figure 4

Mechanism of action of PEA and LUT. The effects protective on olfactory epithelium are restorative on post-COVID-19 anosmia (see text for description).

Figure 5

Cerebrolysin stimulates a neurotrophic effect on neuronal cells. The therapeutic effect of Cerebrolysin is attributable to a potential neuro-restorative effect of the olfactory neuroepithelium (see text for description).

Figure 6

Treatments for olfactory impairment in post-COVID-19 patients. The potential therapeutic approaches, pharmacological, biological, molecular, and genetic, are described in the text. To date, all methods suggested are under experimental trials.