Intranasal theophylline as an adjunct to corticosteroid therapy in post-COVID-19 anosmia: a randomized clinical trial

Olfactory dysfunction is a common neurological manifestation of coronavirus disease 2019 (COVID-19) and may persist for months after viral recovery. Effective treatment options remain limited.

To evaluate the efficacy of intranasal theophylline combined with nasal corticosteroids compared with nasal corticosteroids alone in patients with persistent post-COVID-19 anosmia.

This prospective randomized clinical trial included 50 adult patients with PCR-confirmed post-COVID-19 anosmia. Participants were randomly allocated into two groups using block randomization. Group A received intranasal theophylline plus mometasone nasal spray, while Group B received mometasone nasal spray alone. Treatment continued for two months. The primary outcome measure was the self-reported Global Rating of Smell Change (GRSC)⁸, while objective olfactory function was evaluated using the San Diego Odor Identification Test (SDOIT)¹¹ at baseline, two weeks, one month, and two months.

Both groups demonstrated progressive improvement in olfactory function. However, the combination therapy group showed significantly greater improvement in GRSC scores compared with the corticosteroid-only group (85.0 ± 2.8% vs. 65.0 ± 3.4%, p < 0.001). Final SDOIT scores were also significantly higher in the combination group (7.2 ± 0.8 vs. 6.1 ± 1.1, p < 0.001).

Intranasal theophylline combined with nasal corticosteroids may enhance olfactory recovery in patients with persistent post-COVID-19 anosmia. Larger randomized studies are required to confirm these findings.