Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19
Zaki F Aref, Shamardan Ezz Eldin S Bazeed, Mohammed H Hassan, Abeer S Hassan, Alaa Rashad, Rehab G Hassan, Aida A Abdelmaksoud
International Journal of Nanomedicine, doi:10.2147/ijn.s313093
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 nanosuspension 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 hematological 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 shortening the anosmia duration. Clinicaltrials.gov Identifier: NCT04716569; https://clinicaltrials.gov/ct2/show/ NCT04716569.
Disclosure No potential conflicts of interest between authors to be declare.
Dovepress
References
Abdelmaksoud, Ghweil, Hassan, Olfactory disturbances as presenting manifestation among egyptian patients with COVID-19: possible role of zinc, Biol Trace Elem Res,
doi:10.1007/s12011-020-02546-5Alam, Murshed, Bhiuyan, Saber, Alam, A case series of 100 COVID-19 positive patients treated with combination of ivermectin and doxycycline, J Bangladesh Coll Phys Surg,
doi:10.3329/jbcps.v38i0.47512Alshweiat, Csóka, Tömösi, Nasal delivery of nanosuspension-based mucoadhesive formulation with improved bioavailability of loratadine: preparation, characterization, and in vivo evaluation, Int J Pharm,
doi:10.1016/j.ijpharm.2020.119166Aly, Rahman, Indicators of critical illness and predictors of mortality in COVID-19 patients, Infect Drug Resist,
doi:10.2147/IDR.S261159Alzahrani, Saadeldin, Ahmad, The potential use of mesenchymal stem cells and their derived exosomes as immunomodulatory agents for COVID-19 patients, Stem Cells Int,
doi:10.1155/2020/8835986Aref, TCPDF
Azeem, Ashraf, Rasheed, Anjum, Hameed, Evaluation of cytotoxicity and antiviral activity of ivermectin against newcastle disease virus, Pak J Pharm Sci
Errecalde, Lifschitz, Vecchioli, Safety and pharmacokinetic assessments of a novel ivermectin nasal spray formulation in a pig model, J Pharm Sci,
doi:10.1016/j.xphs.2021.01.017Gallego, Nishiura, Sah, Rodriguez-Morales, The COVID-19 outbreak and implications for the Tokyo 2020 Summer Olympic Games, Travel Med Infect Dis,
doi:10.1016/j.tmaid.2020.101604Ghweil, Hassan, Khodeary, Characteristics, outcomes and indicators of severity for COVID-19 among sample of ESNA Quarantine Hospital's Patients, Egypt: a retrospective study, Infect Drug Resist,
doi:10.2147/IDR.S263489Götz, Magar, Dornfeld, Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Sci Rep,
doi:10.1038/srep23138Jabeen, Khader, Jabeen, A review on the antiparasitic drug ivermectin for various viral infections and possibilities of using it for novel severe acute respiratory syndrome coronavirus 2: new hope to treat coronavirus disease
Ketkar, Yang, Wormser, Wang, Lack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system, Diagn Microbiol Infect Dis,
doi:10.1016/j.diagmicrobio.2019.03.012Kumar, Singh, Kumari, Current understanding of the influence of environmental factors on SARS-CoV-2 transmission, persistence, and infectivity, Environ Sci Pollut Res Int,
doi:10.1007/s11356-020-12165-1Lehrer, Rheinstein, Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2, Vivo,
doi:10.21873/invivo.12134Liu, Chen, Lin, Han, Clinical features of COVID-19 in elderly patients: a comparison with young and middle-aged patients, J Infect,
doi:10.1016/j.jinf.2020.03.005Lundberg, Pinkham, Baer, Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce venezuelan equine encephalitis virus replication, Antiviral Res,
doi:10.1016/j.antiviral.2013.10.004Mahase, Covid-19: death rate is 0.66% and increases with age, study estimates, BMJ,
doi:10.1136/bmj.m1327Marhl, Grubelnik, Magdič, Markovič, Diabetes and metabolic syndrome as risk factors for COVID-19, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2020.05.013Mastrangelo, Pezzullo, Burghgraeve, Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug, J Antimicrob Chemother,
doi:10.1093/jac/dks147Rajter, Sherman, Fatteh, Vogel, Sacks et al., Use of ivermectin is associated with lower mortality in hospitalized patients with coronavirus disease 2019: the ivermectin in COVID nineteen study, Chest,
doi:10.1016/j.chest.2020.10.009Rodriguez-Morales, Gallego, Escalera-Antezana, COVID-19 in Latin America: the implications of the first confirmed case in Brazil, Travel Med Infect Dis,
doi:10.1016/j.tmaid.2020.101613Rodriguez-Morales, Sánchez-Duque, Hernández-Botero, Preparación y control dela enfermedad por coronavirus 2019 (COVID-19) en América Latina, Acta Medica Peruana,
doi:10.35663/amp.2020.371.909Saindane, Pagar, Vavia, Nanosuspension based in situ gelling nasal spray of carvedilol: development, in vitro and in vivo characterization, Aaps Pharmscitech,
doi:10.1208/s12249-012-9896-yShouman, Hegazy, Nafae, Use of ivermectin as a potential chemoprophylaxis for COVID-19 in Egypt: a randomised clinical trial, J Clin Diagn Res,
doi:10.7860/JCDR/2020/46795.0000Siddiqui, Danciu, Ashraf, Plants-derived biomolecules as potent antiviral phytomedicines: new insights on ethnobotanical evidences against coronaviruses, Plants,
doi:10.3390/plants9091244Siddiqui, Jahan, Ashraf, Current status and strategic possibilities on potential use of combinational drug therapy against COVID-19 caused by SARS-CoV-2, J Biomol Struct Dyn,
doi:10.1080/07391102.2020.1802345Singh, Gupta, Ghosh, Misra, Diabetes in COVID-19: prevalence, pathophysiology, prognosis and practical considerations, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2020.04.004Surti, Patel, Adnan, Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study, RSC Adv,
doi:10.1039/D0RA06379GWagstaff, Rawlinson, Hearps, Jans, An AlphaScreen ® -based assay for high-throughput screening for specific inhibitors of nuclear import, J Biomol Screen,
doi:10.1177/1087057110390360Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem J,
doi:10.1042/BJ20120150Wang, Jin, Ren, Updating the diagnostic criteria of COVID-19 "suspected case" and "confirmed case" is necessary, Mil Med Res,
doi:10.1186/s40779-020-00245-9Xia, Quan, Piao, Preparation of stable nitrendipine nanosuspensions using the precipitation-ultrasonication method for enhancement of dissolution and oral bioavailability, Eur J Pharm Sci,
doi:10.1016/j.ejps.2010.04.006Yang, Zheng, Gou, Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis, Int J Infect Dis,
doi:10.1016/j.ijid.2020.03.017Zhang, Wang, Jia, Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China, Clin Microbiol Infect,
doi:10.1016/j.cmi.2020.04.012
