Clinical suitability of intranasal delivery of M2 macrophage soluble factors in patients with post-COVID olfactory disorders

TL;DR

This study explores the safety and effectiveness of using M2 macrophage factors delivered intranasally to treat long-term smell loss in post-COVID patients.

Contribution

It introduces intranasal delivery of M2 macrophage soluble factors as a novel therapeutic approach for post-COVID olfactory dysfunction.

Findings

Intranasal M2 macrophage conditioned medium improved odor perception and recognition in patients.

Patients reported significant subjective improvement in smell after treatment.

The therapy was safe, well-tolerated, and showed high patient satisfaction over a 6-12 month follow-up.

Abstract

SARS-CoV virus showed transneuronal penetration through the olfactory bulb resulting in the rapid intracranial spread. So, olfactory dysfunction is an early marker of COVID-19 infection. However, individuals may develop chronic olfactory impairment for more than six months in 1–10% of cases.

The study’s objective was to evaluate the efficacy and safety of intranasal immunotherapy using bioactive substances produced by M2 macrophages for the treatment of people with long-term post-COVID-19 hyposmia.

Seven individuals with long-term persistent hyposmia (7 to 24 months), associated with PCR-confirmed coronavirus infection were evaluated for olfactory function at baseline, one, and six to twelve months after therapy.

The intranasal inhalation of M2 macrophage conditioned medium (one time per day for 28-30 days) was well tolerated. Furthermore, olfactometry demonstrated that the patients restored their capacity to perceive (Kruskal-Wallis H test 14.123, p = 0.0009) and recognize odors (H = 11.674, p = 0.0029). In addition, the subjective evaluation of smell significantly improved (H = 11.935, p = 0.0026). At the 6-
to 12-month follow-up, the majority of patients (5/7) reported extremely high levels of satisfaction with the outcomes, and the remaining two patients also felt generally positive about the therapy’s success.

Overall, our study showed that the use of intranasal inhalations as a method of delivering bioactive factors and the conditioned medium of M2 macrophages as a therapeutic agent are both safe, well tolerated and, according to preliminary data, clinically effective in the treatment of patients with long-term post-COVID-19 hyposmia.

None Declared