BACKGROUND: The growing number of COVID-19 patients with long-lasting olfactory disorders makes it necessary to identify effective treatments that enhance the spontaneous recovery of olfactory function. METHODS: Multicentre randomised case-control study that involved 18 patients with COVID-19 related anosmia or severe hyposmia for more than 30 days. Nine patients were prescribed systemic prednisone and nasal irrigation with betamethasone, ambroxol and rinazine for 15 days. The other 9, untreated, patients were used as controls. The olfactory function was evaluated with CCCRC test at 20 and 40 days from the first evaluation. RESULTS: In the control group, a median olfactory score of 20 (IQR 30) was detected at baseline. At the 20-day control there was no significant improvement in olfactory function. The improvement in olfactory performance became significant at the 40-day follow-up compared to baseline scores [60 (IQR 60) versus 20 (IQR 30)]. In the treatment group, patients had a mean olfactory score of 10 (IQR 15) at initial control. At the 20-day control, a significant im-provement in the olfactory scores, compared to the baseline, was detected [70 (IQR 40) versus 10 (IQR 15)]. Olfactory function further improved at 40 days [median score 90 (IQR 50)]. Patients in the treatment group reported significantly higher improvements of the olfactory scores than the controls at both the 20-day [40 (IQR 45) versus 10 (IQR 15)] and 40-day [60 (IQR 40) versus 30 (IQR 25)] evaluations. CONCLUSIONS: Based on the results of this study, the mix of drugs including steroids could represent a useful specific therapy to reduce the prevalence of this long-term morbidity.