Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia

Zaki F Aref,1 Shamardan Ezz Eldin S Bazeed,2 Mohammed H Hassan,3 Abeer S Hassan,4 Ali A Ghweil,2 Mennatallah Ali Abdelrhman Sayed,5 Alaa Rashad,6 Haggagy Mansour,6 Aida A Abdelmaksoud1 1ENT Department, Faculty of Medicine, South Valley University, Qena, Egypt; 2Tropical Medicine and Gastroenterology Department, Faculty of Medicine, South Valley University, Qena, Egypt; 3Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt; 5King Salman International University, El Tor, Egypt; 6Department of Chest Diseases and Tuberculosis, Faculty of Medicine, South Valley University, Qena, EgyptCorrespondence: Mohammed H Hassan, Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt, Tel +20 1098473605, Email Mohammedhosnyhassaan@yahoo.com; mohammedhosnyhassaan@med.svu.edu.egPurpose: Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia.Methods: It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group “ivermectin group” included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients “placebo group” who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done.Results: The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05.Conclusion: In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment.Trial Registration No: NCT04951362.Keywords: post-COVID-19 anosmia, ivermectin, nanosuspension mucoadhesive nasal spray