RETRACTED: Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon

Samaha et al., Viruses, doi:10.3390/v13060989 (results 1/16), Jan 2021
RETRACTED

Ivermectin for COVID-19

4th treatment shown to reduce risk in August 2020, now with p < 0.0000000001 from 106 studies, recognized in 24 countries.

No treatment is 100% effective.
Protocols combine treatments.

This study was retracted.
Samaha et al., 16 Jan 2021, peer-reviewed, 16 authors.
Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon
Ali A Samaha, Hussein Mouawia, Mirna Fawaz, Hamad Hassan, Ali Salami, Ali Al Bazzal, Hamid Bou Saab, Mohamed Al-Wakeel, Ahmad Alsaabi, Mohamad Chouman, Mahmoud Al Moussawi, Hassan Ayoub, Ali Raad, Ola Hajjeh, Ali H Eid, Houssam Raad
Viruses, doi:10.3390/v13060989
Objective: This study was designed to determine the efficacy of ivermectin, an FDAapproved drug, in producing clinical benefits and decreasing the viral load of SARS-CoV-2 among asymptomatic subjects that tested positive for this virus in Lebanon. Methods: A randomized controlled trial was conducted in 100 asymptomatic Lebanese subjects that have tested positive for SARS-CoV2. Fifty patients received standard preventive treatment, mainly supplements, and the experimental group received a single dose (according to body weight) of ivermectin, in addition to the same supplements the control group received. Results: There was no significant difference (p = 0.06) between Ct-values of the two groups before the regimen was started (day zero), indicating that subjects in both groups had similar viral loads. At 72 h after the regimen started, the increase in Ct-values was dramatically higher in the ivermectin than in the control group. In the ivermectin group, Ct increased from 15.13 ± 2.07 (day zero) to 30.14 ± 6.22 (day three; mean ± SD), compared to the control group, where the Ct values increased only from 14.20 ± 2.48 (day zero) to 18.96 ± 3.26 (day three; mean ± SD). Moreover, more subjects in the control group developed clinical symptoms. Three individuals (6%) required hospitalization, compared to the ivermectin group (0%). Conclusion: Ivermectin appears to be efficacious in providing clinical benefits in a randomized treatment of asymptomatic SARS-CoV-2-positive subjects, effectively resulting in fewer symptoms, lower viral load and reduced hospital admissions. However, larger-scale trials are warranted for this conclusion to be further cemented.
Conflicts of Interest: The authors declare no conflict of interest.
References
Ahmed, Karim, Ross, Hossain, Clemens et al., A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness, Int. J. Infect. Dis, doi:10.1016/j.ijid.2020.11.191
Alexander, Tinkov, Strand, Alehagen, Skalny et al., Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19, Nutrients, doi:10.3390/nu12082358
Arévalo, Pagotto, Pórfido, Daghero, Segovia et al., Ivermectin reduces coronavirus infection in vivo: A mouse experimental model, bioRxiv, doi:10.1101/2020.11.02.363242
Booz, Altara, Eid, Wehbe, Fares et al., Macrophage responses associated with COVID-19: A pharmacological perspective, Eur. J. Pharmacol, doi:10.1016/j.ejphar.2020.173547
Buonfrate, Salas-Coronas, Munoz, Maruri, Rodari et al., Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): A multicentre, open-label, phase 3, randomised controlled superiority trial, Lancet Infect. Dis, doi:10.1016/S1473-3099(19)30289-0
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antivir. Res, doi:10.1016/j.antiviral.2020.104787
Chaccour, Casellas, Blanco-Di Matteo, Pineda, Fernandez-Montero et al., The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial, EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720
Dingens, Crawford, Adler, Steele, Lacombe et al., Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak, Nat. Commun, doi:10.1038/s41467-020-18178-1
Dinicolantonio, Barroso, Mccarty, Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19, Open Heart, doi:10.1136/openhrt-2020-001350
Finzi, Harrington, Zinc treatment of outpatient COVID-19: A retrospective review of 28 consecutive patients, J. Med. Virol, doi:10.1002/jmv.26812
Giordo, Zinellu, Eid, Pintus, Therapeutic Potential of Resveratrol in COVID-19-Associated Hemostatic Disorders, Molecules, doi:10.3390/molecules26040856
Gotz, Magar, Dornfeld, Giese, Pohlmann et al., Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Sci. Rep, doi:10.1038/srep23138
Hall, Jr, Ji, A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease, Travel. Med. Infect. Dis, doi:10.1016/j.tmaid.2020.101646
Hammoud, Wehbe, Abdelhady, Kobeissy, Eid et al., Dysregulation of Angiotensin Converting Enzyme 2 Expression and Function in Comorbid Disease Conditions Possibly Contributes to Coronavirus Infectious Disease 2019 Complication Severity, Mol. Pharmacol, doi:10.1124/molpharm.120.000119
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:10.1101/2020.10.26.20219345
Hu, Guo, Zhou, Shi, Characteristics of SARS-CoV-2 and COVID-19, Nat. Rev. Microbiol
Hussein, Elkhair, Molecular docking identification for the efficacy of some zinc complexes with chloroquine and hydroxychloroquine against main protease of COVID-19, J. Mol. Struct, doi:10.1016/j.molstruc.2021.129979
Jans, Martin, Wagstaff, Inhibitors of nuclear transport, Curr. Opin. Cell Biol, doi:10.1016/j.ceb.2019.01.001
Joob, Wiwanitkit, COVID-19 can present with a rash and be mistaken for dengue, J. Am. Acad. Dermatol, doi:10.1016/j.jaad.2020.03.036
Kaddoura, Alibrahim, Hijazi, Soudani, Audi et al., COVID-19 Therapeutic Options Under Investigation, Front. Pharmacol, doi:10.3389/fphar.2020.01196
Kampf, Lemmen, Suchomel, Ct values and infectivity of SARS-CoV-2 on surfaces, Lancet Infect. Dis, doi:10.1016/S1473-3099(20)30883-5
Kaur, Shekhar, Sharma, Sarma, Prakash et al., Ivermectin as a potential drug for treatment of COVID-19: An in-sync review with clinical and computational attributes, Pharmacol. Rep, doi:10.1007/s43440-020-00195-y
Kinobe, Owens, A systematic review of experimental evidence for antiviral effects of ivermectin and an in-silico analysis of ivermectin's possible mode of action against SARS-CoV-2, Fundam Clin. Pharmacol, doi:10.1111/fcp.12644
Lorenz, Dias Bocewicz, Correa De Azevedo Marques, Reis Santana, Chiaravalloti-Neto et al., Have measures against COVID-19 helped to reduce dengue cases in Brazil? Travel, Med. Infect. Dis
Martin, Jans, Antivirals that target the host IMPalpha/beta1-virus interface, Biochem. Soc. Trans, doi:10.1042/BST20200568
Navarro, Camprubi, Requena-Mendez, Buonfrate, Giorli et al., Safety of high-dose ivermectin: A systematic review and meta-analysis, J. Antimicrob. Chemother, doi:10.1093/jac/dkz524
Noreen, Maqbool, Madni, Dexamethasone: Therapeutic potential, risks, and future projection during COVID-19 pandemic, Eur. J. Pharmacol, doi:10.1016/j.ejphar.2021.173854
Pujadas, Chaudhry, Mcbride, Richter, Zhao et al., SARS-CoV-2 viral load predicts COVID-19 mortality, Lancet Respir. Med, doi:10.1016/S2213-2600(20)30354-4
Rabi, Al Zoubi, Kasasbeh, Salameh, Al-Nasser, SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far, Pathogens, doi:10.3390/pathogens9030231
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
Shakkour, Habashy, Berro, Takkoush, Abdelhady et al., Drug Repurposing in Neurological Disorders: Implications for Neurotherapy in Traumatic Brain Injury, Neuroscientist, doi:10.1177/1073858420961078
Shakoor, Feehan, Al Dhaheri, Ali, Platat et al., Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?, Maturitas
Tay, Fraser, Chan, Moreland, Rathore et al., Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin, Antivir. Res, doi:10.1016/j.antiviral.2013.06.002
Thomas, Patel, Bittel, Wolski, Wang et al., Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial, JAMA Netw. Open, doi:10.1001/jamanetworkopen.2021.0369
Vargas-Estrada, Gutierrez, Juarez-Rodriguez, Sumano, Pharmacokinetics of doxycycline and tissue concentrations of an experimental long-acting parenteral formulation of doxycycline in Wistar rats, Arzneimittelforschung
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin alpha/betamediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem. J, doi:10.1042/BJ20120150
Wehbe, Hammoud, Soudani, Zaraket, El-Yazbi et al., Molecular Insights Into SARS COV-2 Interaction With Cardiovascular Disease: Role of RAAS and MAPK Signaling, Front. Pharmacol, doi:10.3389/fphar.2020.00836
Westblade, Brar, Pinheiro, Paidoussis, Rajan et al., SARS-CoV-2 Viral Load Predicts Mortality in Patients with and without Cancer Who Are Hospitalized with COVID-19, Cancer Cell, doi:10.1016/j.ccell.2020.09.007
Yang, Atkinson, Wang, Lee, Bogoyevitch et al., The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/beta1 heterodimer, Antivir. Res, doi:10.1016/j.antiviral.2020.104760
Younis, Zareef, Al Hassan, Bitar, Eid et al., Hydroxychloroquine in COVID-19 Patients: Pros and Cons, Front. Pharmacol, doi:10.3389/fphar.2020.597985
Zareef, Younis, Bitar, Eid, Arabi, COVID-19 in Pediatric Patients: A Focus on CHD Patients, Front. Cardiovasc. Med, doi:10.3389/fcvm.2020.612460
Zhang, Ni, Zhang, Xu, Gao et al., Ivermectin confers its cytotoxic effects by inducing AMPK/mTORmediated autophagy and DNA damage, Chemosphere, doi:10.1016/j.chemosphere.2020.127448
DOI record: { "DOI": "10.3390/v13060989", "ISSN": [ "1999-4915" ], "URL": "http://dx.doi.org/10.3390/v13060989", "abstract": "<jats:p>Objective: This study was designed to determine the efficacy of ivermectin, an FDA-approved drug, in producing clinical benefits and decreasing the viral load of SARS-CoV-2 among asymptomatic subjects that tested positive for this virus in Lebanon. Methods: A randomized controlled trial was conducted in 100 asymptomatic Lebanese subjects that have tested positive for SARS-CoV2. Fifty patients received standard preventive treatment, mainly supplements, and the experimental group received a single dose (according to body weight) of ivermectin, in addition to the same supplements the control group received. Results: There was no significant difference (p = 0.06) between Ct-values of the two groups before the regimen was started (day zero), indicating that subjects in both groups had similar viral loads. At 72 h after the regimen started, the increase in Ct-values was dramatically higher in the ivermectin than in the control group. In the ivermectin group, Ct increased from 15.13 ± 2.07 (day zero) to 30.14 ± 6.22 (day three; mean ± SD), compared to the control group, where the Ct values increased only from 14.20 ± 2.48 (day zero) to 18.96 ± 3.26 (day three; mean ± SD). Moreover, more subjects in the control group developed clinical symptoms. Three individuals (6%) required hospitalization, compared to the ivermectin group (0%). Conclusion: Ivermectin appears to be efficacious in providing clinical benefits in a randomized treatment of asymptomatic SARS-CoV-2-positive subjects, effectively resulting in fewer symptoms, lower viral load and reduced hospital admissions. However, larger-scale trials are warranted for this conclusion to be further cemented.</jats:p>", "alternative-id": [ "v13060989" ], "author": [ { "affiliation": [], "family": "Samaha", "given": "Ali A.", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0002-6035-6071", "affiliation": [], "authenticated-orcid": false, "family": "Mouawia", "given": "Hussein", "sequence": "additional" }, { "affiliation": [], "family": "Fawaz", "given": "Mirna", "sequence": "additional" }, { "affiliation": [], "family": "Hassan", "given": "Hamad", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-3343-4035", "affiliation": [], "authenticated-orcid": false, "family": "Salami", "given": "Ali", "sequence": "additional" }, { "affiliation": [], "family": "Bazzal", "given": "Ali Al", "sequence": "additional" }, { "affiliation": [], "family": "Saab", "given": "Hamid Bou", "sequence": "additional" }, { "affiliation": [], "family": "Al-Wakeel", "given": "Mohamed", "sequence": "additional" }, { "affiliation": [], "family": "Alsaabi", "given": "Ahmad", "sequence": "additional" }, { "affiliation": [], "family": "Chouman", "given": "Mohamad", "sequence": "additional" }, { "affiliation": [], "family": "Moussawi", "given": "Mahmoud Al", "sequence": "additional" }, { "affiliation": [], "family": "Ayoub", "given": "Hassan", "sequence": "additional" }, { "affiliation": [], "family": "Raad", "given": "Ali", "sequence": "additional" }, { "affiliation": [], "family": "Hajjeh", "given": "Ola", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-3004-5675", "affiliation": [], "authenticated-orcid": false, "family": "Eid", "given": "Ali H.", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-9562-2934", "affiliation": [], "authenticated-orcid": false, "family": "Raad", "given": "Houssam", "sequence": "additional" } ], "container-title": "Viruses", "container-title-short": "Viruses", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2021, 5, 27 ] ], "date-time": "2021-05-27T01:56:44Z", "timestamp": 1622080604000 }, "deposited": { "date-parts": [ [ 2021, 6, 24 ] ], "date-time": "2021-06-24T01:30:07Z", "timestamp": 1624498207000 }, "indexed": { "date-parts": [ [ 2024, 5, 13 ] ], "date-time": "2024-05-13T16:01:31Z", "timestamp": 1715616091750 }, "is-referenced-by-count": 32, "issue": "6", "issued": { "date-parts": [ [ 2021, 5, 26 ] ] }, "journal-issue": { "issue": "6", "published-online": { "date-parts": [ [ 2021, 6 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2021, 5, 26 ] ], "date-time": "2021-05-26T00:00:00Z", "timestamp": 1621987200000 } } ], "link": [ { "URL": "https://www.mdpi.com/1999-4915/13/6/989/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "989", "prefix": "10.3390", "published": { "date-parts": [ [ 2021, 5, 26 ] ] }, "published-online": { "date-parts": [ [ 2021, 5, 26 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1016/j.tmaid.2020.101827", "doi-asserted-by": "publisher", "key": "ref1" }, { "DOI": "10.1038/s41579-020-00459-7", "doi-asserted-by": "publisher", "key": "ref2" }, { "DOI": "10.3390/pathogens9030231", "doi-asserted-by": "publisher", "key": "ref3" }, { "DOI": "10.1177/1073858420961078", "doi-asserted-by": "publisher", "key": "ref4" }, { "DOI": "10.1124/molpharm.120.000119", "doi-asserted-by": "publisher", "key": "ref5" }, { "DOI": "10.3389/fphar.2020.00836", "doi-asserted-by": "publisher", "key": "ref6" }, { "DOI": "10.3389/fcvm.2020.612460", "doi-asserted-by": "publisher", "key": "ref7" }, { "DOI": "10.1016/j.tmaid.2020.101646", "doi-asserted-by": "publisher", "key": "ref8" }, { "DOI": "10.3390/molecules26040856", "doi-asserted-by": "publisher", "key": "ref9" }, { "DOI": "10.3389/fphar.2020.597985", "doi-asserted-by": "publisher", "key": "ref10" }, { "DOI": "10.1016/j.ejphar.2020.173547", "doi-asserted-by": "publisher", "key": "ref11" }, { "DOI": "10.1111/fcp.12644", "doi-asserted-by": "publisher", "key": "ref12" }, { "DOI": "10.1101/2020.11.02.363242", "doi-asserted-by": "publisher", "key": "ref13" }, { "DOI": "10.1016/j.chemosphere.2020.127448", "doi-asserted-by": "publisher", "key": "ref14" }, { "DOI": "10.1016/j.antiviral.2020.104760", "doi-asserted-by": "publisher", "key": "ref15" }, { "DOI": "10.1042/BJ20120150", "doi-asserted-by": "publisher", "key": "ref16" }, { "DOI": "10.1016/j.antiviral.2013.06.002", "doi-asserted-by": "publisher", "key": "ref17" }, { "DOI": "10.1038/srep23138", "doi-asserted-by": "publisher", "key": "ref18" }, { "DOI": "10.1016/j.antiviral.2020.104787", "doi-asserted-by": "publisher", "key": "ref19" }, { "DOI": "10.1016/j.ceb.2019.01.001", "doi-asserted-by": "publisher", "key": "ref20" }, { "DOI": "10.1042/BST20200568", "doi-asserted-by": "publisher", "key": "ref21" }, { "DOI": "10.1016/j.jaad.2020.03.036", "doi-asserted-by": "publisher", "key": "ref22" }, { "DOI": "10.3389/fphar.2020.01196", "doi-asserted-by": "publisher", "key": "ref23" }, { "DOI": "10.1038/s41467-020-18178-1", "doi-asserted-by": "publisher", "key": "ref24" }, { "DOI": "10.1007/s43440-020-00195-y", "doi-asserted-by": "publisher", "key": "ref25" }, { "DOI": "10.1001/jamanetworkopen.2021.0369", "doi-asserted-by": "publisher", "key": "ref26" }, { "DOI": "10.1002/jmv.26812", "doi-asserted-by": "publisher", "key": "ref27" }, { "DOI": "10.1136/openhrt-2020-001350", "doi-asserted-by": "publisher", "key": "ref28" }, { "DOI": "10.1016/j.ijid.2020.11.191", "doi-asserted-by": "publisher", "key": "ref29" }, { "DOI": "10.1093/jac/dkz524", "doi-asserted-by": "publisher", "key": "ref30" }, { "DOI": "10.1016/S1473-3099(20)30883-5", "doi-asserted-by": "publisher", "key": "ref31" }, { "DOI": "10.1016/j.maturitas.2020.08.003", "doi-asserted-by": "publisher", "key": "ref32" }, { "DOI": "10.3390/nu12082358", "doi-asserted-by": "publisher", "key": "ref33" }, { "DOI": "10.1016/j.ejphar.2021.173854", "doi-asserted-by": "publisher", "key": "ref34" }, { "DOI": "10.1016/j.molstruc.2021.129979", "doi-asserted-by": "publisher", "key": "ref35" }, { "DOI": "10.1016/j.ccell.2020.09.007", "doi-asserted-by": "publisher", "key": "ref36" }, { "DOI": "10.1016/S2213-2600(20)30354-4", "doi-asserted-by": "publisher", "key": "ref37" }, { "DOI": "10.1016/S1473-3099(19)30289-0", "doi-asserted-by": "publisher", "key": "ref38" }, { "DOI": "10.1016/j.chest.2020.10.009", "doi-asserted-by": "publisher", "key": "ref39" }, { "DOI": "10.1055/s-0031-1296512", "doi-asserted-by": "publisher", "key": "ref40" }, { "DOI": "10.1101/2020.10.26.20219345", "doi-asserted-by": "publisher", "key": "ref41" }, { "DOI": "10.1016/j.eclinm.2020.100720", "doi-asserted-by": "publisher", "key": "ref42" } ], "reference-count": 42, "references-count": 42, "relation": {}, "resource": { "primary": { "URL": "https://www.mdpi.com/1999-4915/13/6/989" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon", "type": "journal-article", "volume": "13" }