Efficacy of Adjunctive Sodium Citrate in Smell Retraining for People With Post-Acute Sequelae COVID-19 Olfactory Dysfunction

Background: Loss of sense of smell is a hallmark of COVID-19 infection. While about 80% of post-COVID olfactory dysfunction (OD) will experience some spontaneous recovery within 2 months of initial infection, about 20% will continue to suffer long-term.1 Participants with persistent OD suffer great disability including loss of pleasure with eating leading to weight loss and/or gain and other health risks, including possible dementia. Further, loss of smell may lead to harm, with chief examples of inability to smell gas leaks or food that has gone bad. Currently, use of "smell retraining" is recognized internationally as the most accepted method to treat patients with OD, including post-viral or post-infectious OD.2 Some authors have extrapolated that smell retraining may be of benefit in post-COVID OD, however, data is sparse.3

Increased extracellular calcium has been shown to inhibit the olfaction cascade occurring in the nose by either phosphorylating adenylate cyclase or by interacting and decreasing cyclic nucleotide-gated channels sensitivity to cyclin nucleotides. Several studies have been performed to date using sodium citrate administered as a nasal spray to effectively reduce extracellular calcium resulting in temporary sense of smell benefit in those who have smell loss from a variety of causes, most significantly, post-viral or post-infectious loss (PIOD).

Several studies over the last two decades have examined the effect of sodium citrate on olfactory function in those with OD (mainly post-infectious OD) all of which have shown acute improvement in smell, peaking typically around 1 hour after application.4-7 Most recently, in 2021 Whitcroft et al conducted a controlled clinical trial on 60 PIOD participants. They applied sodium citrate intranasal spray to participants' right nostril for two weeks and olfaction was evaluated by Sniffin' Sticks composite TDI score both before the trial and after 2 weeks of sodium citrate use. They found a significant improvement in TDI score, though not reaching clinical significance. Further, while the proportion of participants reporting parosmia did not change, there was a significant reduction in participants reporting phantosmia.8

The hypothesis is that the administration of sodium citrate to the nasal cavity, providing a temporary improvement in sense of smell, before the performance of smell retraining may augment its effects and yield better recovery in post-COVID-19 OD.

Purpose: The goal of this pilot study is to assess the feasibility and impact of using sodium citrate nasal spray as an adjunct to olfactory retraining in participants with long-term post-COVID-19 olfactory dysfunction.