Global trends in clinical studies of ivermectin in COVID-19
Ph.D Morimasa Yagisawa, M.D Patrick J Foster, Ph.D Hideaki Hanaki, Ph.D Satoshi Ōmura
Response to the initial alarm bells of the Coronavirus infection, which occurred in Wuhan City, Hubei Province, China in November 2019, was delayed as it was announced to be a type of pneumonia of unknown cause. The WHO warned about traveling to China in January 2020. After much urging, the world was finally properly warned, but the Chinese government did not accurately announce the outbreak situation. Consequently, the delaying of the construction of an epidemic prevention system worldwide has resulted in the direst infection circumstances facing the world today. One year has passed since the WHO named the new coronavirus SARS-CoV-2 infection, COVID-19, and it was declared a pandemic on the 11 th of March 2020, based on the judgment that it corresponds to "an internationally concerned public health emergency". Suppression of virus transmission by vaccine has finally begun. To date, the pandemic has affected more than 115 million people and killed more than 2.5 million people in 220 countries/ regions around the world. There appears to a potential for control in the near future. However, there is a limit to the supply of vaccines and developed countries are competing to obtain the required amount of vaccination necessary for their own citizens. Although the WHO is trying to secure a certain amount for developing countries, it is predicted that a considerable period of time will be required before COVID-19 becomes controllable. On the other hand, with regard to therapeutic agents for COVID-19, studies began at an early stage. The therapeutic effects of hydroxychloroquine or chloroquine, lopinavir/ritonavir combination, tocilizumab, interferon β1, as well as others, were found to have limited efficacies or no effect. Remdesivir improves recovery time by as much as 30% in critically ill patients, but it is not suitable for mild to moderately ill patients-which comprises the majority of infected individuals. Although the Mar. 2021 THE JAPANESE JOURNAL OF ANTIBIOTICS 74-1 45 ( 45 ) steroid drug dexamethasone is effective in alleviating inflammatory symptoms, its use in mild to moderately ill patients without significant inflammatory symptoms is not recommended. Currently, there are no therapeutic agents available for mildly ill patients who are being treated at home (or in self-isolating accommodations) or for moderately ill hospitalized patients. Nothing is as helpless as a disease without a cure. In a situation where the number of COVID-19 patients is rapidly expanding, the number of deaths increasing worldwide, hydroxychloroquine, doxycycline, azithromycin, and other drugs are ineffective for therapeutic purposes, an effective treatment method is being sought. An Australian research group reported that ivermectin suppresses SARS-CoV-2 replication in an in vitro infection experiment. Ivermectin has been widely used since 1987 for the control of river blindness and lymphatic filariasis, as well as in the treatment of scabies in humans...
Conflict of Interest None to declare.
References
Ahmed, Karim, Ross, A five day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness, Int J Infect Dis. Pre-print,
doi:10.1016/j.ijid.2020.11.191Alam, Murshed, Bhiuyan, Saber, Alam et al., A case series of 100 COVID-19 positive patients treated with combination of ivermectin and doxycycline, J Bangladesh Coll Phys Surg
Analysis, Ivermectin is effective for COVID-19: real-time meta analysis of 42 studies
Astrazeneca, Co, Ltd, submits application for manufacturing and marketing approval of new coronavirus vaccine in Japan
Authenticated, Government Information. 21st Century Cures Act, Public Law
Babalola, Bode, Ajayi, Ivermectin shows clinical benefits in mild to moderate COVID19: a randomised controlled double-blind dose-response study in Lagos, QJM Int J Med,
doi:10.1093/qjmed/hcab035Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the treatment of Covid-19 -Final report, N Engl J Med
Bernigaud, Guillemot, Ahmed-Belkacem, Oral ivermectin for a scabies outbreak in a long-term-care facility: Potential value in preventing COVID-19 and associated mortality?, Brit J Dermatol. Accepted article,
doi:10.1111/bjd.19821Bhimra, Morgan, Shumaker, Infectious Diseases Society of America Guidelines on the treatment and management of patients with coronavirus disease
Bhimra, Morgan, Shumaker, Infectious Diseases Society of America Guidelines on the treatment and management of patients with coronavirus disease 2019 (COVID-19), Clin Infect Dis,
doi:10.1093/cid/ciaa478Bryner, 1st known case of coronavirus traced back to November in China, Live Science
Cadegiani, Goren, Wambier, Mccoy, Early COVID-19 therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in outpatient setting significantly reduced symptoms compared to known outcomes in untreated patients,
doi:10.1101/2020.10.31.20223883Carvallo, Hirsch, Farinella, Safety and efficacy of the combined use of ivermectin, dexamethasone, exoxaparin and aspirin against COVID-19,
doi:10.1101/2020.09.10.20191619Carvallo, Roberto, Psaltis, Veronica, Study of the efficacy and safety of topical ivermec-tin＋iota-carrageenan in the prophylaxis against COVID-19 in health personnel, J Biomed Res Clin Invest,
doi:10.31546/2633Chaccour, Casellas, Blanco-Di Matteo, The effect of early treatment with ivermectin on viral load, symptoms
Chaccour, Hammann, Garcia, Rabinovich, Ivermectin and COVID-19: Keeping rigor in times of urgency, Am J Trop Med Hyg
Chachar, Khan, Asif, Khushbakht, Khaqan et al., Effectiveness of ivermectin in SARS-CoV-2/COVID-19 patients, Int J Sci,
doi:10.18483/ijSci.2378Chamie-Quintero, Hibberd, Scheim, Ivermectin for COVID-19 in Peru: 14-fold reduction in nationwide excess deaths,
doi:10.31219/osf.io/9egh4Chamie-Quintero, Hibberd, Scheim, Sharp reductions in COVID-19 case fatalities and excess deaths in Peru in close time conjunction, state-by-state, with ivermectin treatments
Chowdhury, Shahbaz, Karim, Islam, Guo et al., A randomized trial of ivermectin-doxycycline and hydroxychloroquine-azithromycin therapy on COVID-19 patients,
doi:10.21203/rs.3.rs-38896/v1Crump, Ivermectin: enigmatic multifaced ʻwonderʼ drug continues to surprise and exceed expectations, J Antibiot
Dasgupta, Sen, Bakshi, Nsp7 and spike glycoprotein of SARS-CoV-2 are envisaged as potential targets of vitamin D and ivermectin, Preprints
Dayer, Coronavirus (2019-nCoV) deactivation via spike glycoprotein shielding by old drugs, bioinformatic study
De Melo, Lazarini, Larrous, Anti-COVID-19 efficacy of ivermectin in the golden hamster,
doi:10.1101/2020.11Drozdzal, Rosik, Lechowicz, FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy, Drug Resist Updat,
doi:10.1016/j.drup.2020.100719Elgazzar, Hany, Youssef, Hany, Hafez et al., Efficacy and safety of ivermectin for treatment and prophylaxis of COVID-19 pandemic, Research Square preprint,
doi:10.21203/rs.3.rs-100956/v1Espitia-Hernandez, Munguia, Diaz-Chiguer, Lopez-Elizalde, Jimenez-Ponce, Effects of ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study, Biomed Res
Flccc Alliance, Dr, Kory, president of the FLCCC Alliancce tells Senate Committee on Homeland Security and Governmental Affairs looking into arly outpatient COVID-19 treatment
Flccc Alliance, FLCCC Alliance response to Merckʼs public statements on ivermectinʼs efficacy in COVID-19
Flccc Alliance, FLCCC Alliance response to the NIH guideline committee recommendation on ivermectin use in COVID-19 dated
Flccc Alliance, NIH revises treatment guidelines for ivermectin for the treatment of COVID-19. Ivermectin is now a therapeutic option for doctors & prescribers
Flccc Alliance, One Page Summary of the Clinical Trials Evidence for Ivermectin in COVID-19
Flccc Alliance, investigators of the Oxford PRINCIPLE Trial on ivermectin in COVID-19
Flvenson, COVID-19: association with rapidly progressive forms of alopecia areata, Int J Dermatol
Food, Drug Administration: FDA issues emergency use authorization for convalescent plasma as potential promising COVID-19 treatment, another achievement in administrationʼs fight against pandemic
Gorial, University, Baghdad, Efficacy of ivermectin as add on therapy in COVID19 patients
Guerrero, Bravo, Munoz, Ardila, Guerrero, COVID-19: The ivermectin African enigma, Colomb Med
Gupta, Sahoo, Singh, Ivermectin: potential candidate for the treatment of Covid-19, Braz Infect Dis
Hashim, Maulood, Rasheed, Fatak, Kabah et al., Controlled randomized clinical trial on using ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq,
doi:10.1101/2020.10Hill, Abdulamir, Ahmed, Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection
Holshue, Debolt, Lindquist, Lofy, Wiesman et al., First case of 2019 novel coronavirus in the United States, N Engl J Med
Inc, Biontech, In vitro studies demonstrate Pfizer and BioNTech COVID-19 vaccine elicits antibodies that neutralize SARS-CoV-2 with key mutations present in U.K. and South African variants
Jabeen, 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-2019, Asian J Pharm Clin Res
Kalhor, Sadeghi, Abolhasani, Kalhor, Rahimi, Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2ʼs protein and human ACE2 interaction through virtual screening approaches, J Biomol Struct Dyn,
doi:10.1080/07391102.2020.1824816Kanoh, Rubin, Mechanisms of action and clinical application of macrolides as immunomodulatory medications, Clin Microbiol Rev
Khater, Das, Repurposing ivermectin to inhibit the activity of SARS CoV-2 helicase: possible implications for COVID 19 therapeutics
Kory, Meduri, Iglesias, Varon, Berkowitz et al., Review of the emerging evidence demonstrating the efficacy of ivermectin in the prophylaxis and treatment of COVID-19
Krolewiecki, Lifschitz, Moragas, Antiviral effect of high-dose ivermectin in adults with COVID-19: a pilot randomised, controlled, open label, multicentre trial
Kudoh, Azuma, Tamaoki, Takizawa, Nakata et al., Novel action of erythromycin and its derivatives
Kudoh, Azuma, Yamamoto, Izumi, Ando, Improvement of survival in patient with diffuse panbronchiolitis treated with low-dose erythromycin, Am J Respir Crit Care Med
Kunihiro, Kitasato, A placebo-controlled, randomized, double-blind study in COVID-19 patients with ivermectin; An investigator initiated trial
Labour, Welfare, Cabinet Order: To designate the new coronavirus infectious disease as the type of infectious disease under Article 34 of the Quarantine Law
Lawrie, Ivermectin reduces the risk of death from COVID-19 -a rapid review and meta-analysis in support of the recommendation of the Front Line COVID-19 Critical Care Alliance
Lehrer, Rheinstein, Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2, vivo
Mahmud, Clinical trial of ivermectin plus doxycycline for the treatment of COVId-19 infection
Mectizan, Program, Mectizan Expert Committee statement on potential efficacy of ivermectin on COVID-19
Moderna, emerging variants first identified in the U.K. and the Republic of South Africa
Mohan, Tiwari, Suri, Ivermectin in mild and moderate COVID-19 (RIVET-COV): a randomized, placebo-controlled trial
Mondal, Quintili, Karamchandani, Bose, Thromboembolic disease in COVID-19 patients: A brief narrative review, J Intensive Care,
doi:10.1186/s40560-020-00483-yMorgenstern, Redondo, Leon, The use of compassionate ivermectin in the management of symptomatic outpatients and hospitalized patients with clinical diagnosis of COVID-19 at the Medical Center Bournigal and the Medical Center PuntaCana, rescue group,
doi:10.1101/2020.10.29.20222505Munster, Koopmans, Van Doremalen, Van Riel, De, A novel coronavirus emerging in China -Key questions for impact assessment, N Engl J Med,
doi:10.1056/NEJMp2000929Niaee, Gheibi, Namdar, Allami, Zolghadr et al., Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial,
doi:10.21203/rs.3.rs-109670/v1Okumus, Ivermectin for severe COVID-19 management
Olsen, Chen, Liu, Early introduction of severe acute respiratory syndrome coronavirus 2 into Europe, Emerg Infect Dis,
doi:10.3201/eid2607.200359Pena-Silva, Duffull, Steer, Jaramillo-Rincon, Gwee et al., Pharmacokinetic consideration on the repurposing of ivermectin fro treatment of COVID-19, Br J Clin Pharmacol,
doi:10.1111/bcp.14476Pharmaceutical, Ltd, Start of a Japanese clinical study of TAK-919, Modernaʼs COVID-19 vaccine candidate
Podder, Chowdhury, Sina, Haque, Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-center, open-label, randomized controlled study, IMC J Med Sci
Puntmann, Carerj, Wieters, Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19), JAMA Cardiol
Rahman, Iqbal, Islam, Niaz, Hussain et al., Comparison of viral clearance between ivermectin with doxycycline and hydroxychloroquine with azithromycin in COVID-19 patients, J Bangladesh Coll Phys Surg
Rajter, 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
Rezai, Effectiveness of Ivermectin in the Treatment of Coronavirus Infection in Patients admitted to Educational Hospitals of Mazandaran in
Rubin, Baden, Morrissey, Campion, Medical journals and the 2019-nCoV outbreak, Editorials. N Eng J Med. online,
doi:10.1056/NEJMe2001329Scheim, From cold to killer: How SARS-CoV-2 evolved without hemagglutinin esterase to agglutinate, the clot blood cells in pulmonary and systemic microvasculature
Scheim, Ivermectin for COVID-19 treatment: clinical response at quasi-threshold doses via hypothesized alleviation of CD147-mediated vascular occlusion
Schmith, Zhou, Lohmer, The approved dose of ivermectin alone is not the ideal dose for the treatment of COVID-19, Clin Pharmacol Therap,
doi:10.1002/cpt.1889Schonegger, Gietl, Heinzle, Freudenschuss, Walder, Smell and taste disorders in COVID-19 patients: objective testing and magnetic resonance imaging in five cases, SN Comp Clin Med
Sharp, Corp, Merck statement on ivermectin use during the COVID-19 pandemic
Shouman, Use of ivermectin as a prophylactic option in asymptomatic family close contact for patient with COVID-19
Spoorthi, Sasank, Utility of ivermectin and doxycycline combination for the treatment of SARS-CoV-2, IAIM
Swargiary, Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies,
doi:10.21203/rs.3.rs-73308/v1Takizawa, Desaki, Ohtoshi, Erythromycin suppresses interleukin 6 expression by human bronchial epithelial cells: A potential mechanism of its anti-inflammatory action, Biochem Biophys Res Commun
Tamaoki, Isono, Sakai, Kanemura, Konno, Erythromycin inhibits Cl secretion across canine tracheal epithelial cells, Eur Respir J
Vora, Arora, Behera, Tripathy, White paper on ivermectin as a potent therapy for COVID-19, Indian J Tuberc
Wagstaff, 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
Yamaoka, -01
Ōmura, A splendid gift from the earth: The origins and impact of the avermectins (Nobel Lecture), Angew Chem Int Ed
Ōmura, Crump, The life and times of ivermectin -a success story, Nat Rev Microbiol
Ōmura, Ivermectin: 25 years and still going strong, Int. J Antimicrob Agents
Ōmura, Tsuzuki, Sunazuka, Toyota, Takahashi et al., Gastrointestinal motor-stimulating activity of macrolide antibiotics and the structure-activity relationships, J Antibiot
