Abstract: International Journal of Nanomedicine Dovepress open access to scientific and medical research International Journal of Nanomedicine For personal use only. Open Access Full Text Article ORIGINAL RESEARCH Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19 Zaki F Aref 1 Shamardan Ezz Eldin S Bazeed Mohammed H Hassan 3 Abeer S Hassan 4 Alaa Rashad5 Rehab G Hassan6 Aida A Abdelmaksoud1 2 1 ENT Department, Faculty of Medicine, South Valley University, Qena, Egypt; 2 Tropical Medicine and Gastroenterology Department, Faculty of Medicine, South Valley University, Qena, Egypt; 3 Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt; 4Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt; 5 Department of Chest Diseases and Tuberculosis, Faculty of Medicine, South Vally University, Qena, Egypt; 6 Department of Public Health and Community Medicine, Faculty of Medicine, South Valley University, Qena, Egypt Correspondence: Mohammed H Hassan Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, Egypt Tel +201098473605 Email mohammedhosnyhassaan@med. svu.edu.eg Background: Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro. Objective: We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nano­ suspension intranasal spray in treatment of patients with mild COVID-19. Methods: This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hemato­ logical and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. Results: Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). Conclusion: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and short­ ening the anosmia duration. Clinicaltrials.gov Identifier: NCT04716569; https://clinicaltrials.gov/ct2/show/ NCT04716569. Keywords: ivermectin nanosuspension, nasal spray, COVID-19, biochemical and molecular