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Results of a systematic review and meta-analysis of early studies on ivermectin in SARS-CoV-2 infection

Ragó et al., GeroScience, doi:10.1007/s11357-023-00756-y
Mar 2023  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020, now with p < 0.00000000001 from 105 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments.
5,000+ studies for 104 treatments. c19ivm.org
Systematic review and meta analysis of trials within the first year of the pandemic, showing significantly faster viral clearance with ivermectin.
7 meta analyses show significant improvements with ivermectin for mortality1-6, hospitalization7, recovery3, and cases3.
Currently there are 105 ivermectin for COVID-19 studies, showing 47% lower mortality [34‑58%], 35% lower ventilation [17‑50%], 40% lower ICU admission [12‑58%], 34% lower hospitalization [21‑44%], and 81% fewer cases [71‑87%].
Ragó et al., 7 Mar 2023, peer-reviewed, 13 authors. Contact: zsuzsanna.rago@hpvcentrum.hu, bella.zsolt@med.u-szeged.hu, dembrovszky.fanni@pte.hu, kissszabolcs1995@gmail.com, nelli.farkas@aok.pte.hu, szalenko-tokes.agnes@med.u-szeged.hu, toth.barbara.eva@szte.hu, hegyi.peter@semmelweis-univ.hu, csupor.dezso@pharm.u-szeged.hu, matuz.maria@med.u-szeged.hu, hegedus.imre1@med.semmelweis-univ.hu, mathe.domokos@med.semmelweis-univ.hu, domokos.mathe@hcemm.eu.
This PaperIvermectinAll
Results of a systematic review and meta-analysis of early studies on ivermectin in SARS-CoV-2 infection
Zsuzsanna Ragó, Barbara Tóth, Ágnes Szalenko-Tőkés, Zsolt Bella, Fanni Dembrovszky, Nelli Farkas, Szabolcs Kiss, Péter Hegyi, Mária Matuz, Noémi Tóth, Imre Hegedüs, Domokos Máthé, Dezső Csupor
GeroScience, doi:10.1007/s11357-023-00756-y
Ivermectin, an antiparasitic drug, has been repurposed for COVID-19 treatment during the SARS-CoV-2 pandemic. Although its antiviral efficacy was confirmed early in vitro and in preclinical studies, its clinical efficacy remained ambiguous. Our purpose was to assess the efficacy of ivermectin in terms of time to viral clearance based on the metaanalysis of available clinical trials at the closing date of the data search period, one year after the start of the pandemic. This meta-analysis was reported by following the PRISMA guidelines and by using the PICO format for formulating the question. The study protocol was registered on PROSPERO. Embase, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), bioRvix, and medRvix were searched for human studies of patients receiving ivermectin therapy with control groups. No language or publication status restrictions were applied. The search ended on 1/31/2021 exactly one year after WHO declared the public health emergency on novel coronavirus. The meta-analysis of three trials involving 382 patients revealed that the mean time to viral clearance was 5.74 days shorter in case of ivermectin treatment compared to the control groups [WMD = −5.74, 95% CI (−11.1, −0.39), p = 0.036]. Ivermectin has significantly reduced the time to viral clearance in mild to moderate COVID-19 diseases
Conflict of interest reported Abd-Elsalam et al. [36] 31 May
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Accessed.'}, { 'key': '756_CR22', 'doi-asserted-by': 'publisher', 'volume-title': 'Cochrane handbook for systematic reviews of interventions', 'author': 'JP Higgins', 'year': '2019', 'unstructured': 'Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. ' 'Cochrane handbook for systematic reviews of interventions: John Wiley & ' 'Sons; 2019.', 'DOI': '10.1002/9781119536604'}, { 'key': '756_CR23', 'doi-asserted-by': 'crossref', 'unstructured': 'Sterne J, Hernán M, Reeves B, Savović J, Berkman N, Viswanathan M. ' 'ROBINS-I: a tool for assessing risk of bias in non-randomised studies of ' 'interventions BMJ. 2016; 355: i4919. Int J Epidemiol. 2018;1.', 'DOI': '10.1136/bmj.i4919'}, { 'issue': '7650', 'key': '756_CR24', 'doi-asserted-by': 'publisher', 'first-page': '924', 'DOI': '10.1136/bmj.39489.470347.AD', 'volume': '336', 'author': 'GH Guyatt', 'year': '2008', 'unstructured': 'Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et ' 'al. GRADE: an emerging consensus on rating quality of evidence and ' 'strength of recommendations. Bmj. 2008;336(7650):924–6.', 'journal-title': 'Bmj.'}, { 'issue': '11', 'key': '756_CR25', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0242184', 'volume': '15', 'author': 'D Camprubí', 'year': '2020', 'unstructured': 'Camprubí D, Almuedo-Riera A, Martí-Soler H, Soriano A, Hurtado JC, ' 'Subirà C, et al. Lack of efficacy of standard doses of ivermectin in ' 'severe COVID-19 patients. PloS one. 2020;15(11):e0242184.', 'journal-title': 'PloS one.'}, { 'key': '756_CR26', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.eclinm.2020.100720', 'volume': '32', 'author': 'C Chaccour', 'year': '2021', 'unstructured': 'Chaccour C, Casellas A, Blanco-Di Matteo A, Pineda I, Fernandez-Montero ' 'A, Ruiz-Castillo P, 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. EClinicalMed. 2021;32:100720.', 'journal-title': 'EClinicalMed.'}, { 'issue': '11', 'key': '756_CR27', 'doi-asserted-by': 'publisher', 'first-page': '780', 'DOI': '10.1093/qjmed/hcab035', 'volume': '114', 'author': 'OE Babalola', 'year': '2021', 'unstructured': 'Babalola OE, Bode CO, Ajayi AA, Alakaloko FM, Akase IE, Otrofanowei E, ' 'et al. Ivermectin shows clinical benefits in mild to moderate COVID19: a ' 'randomized controlled double-blind, dose-response study in Lagos. QJM. ' '2021;114(11):780–8.', 'journal-title': 'QJM.'}, { 'key': '756_CR28', 'doi-asserted-by': 'publisher', 'first-page': '214', 'DOI': '10.1016/j.ijid.2020.11.191', 'volume': '103', 'author': 'S Ahmed', 'year': '2021', 'unstructured': 'Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, et al. A ' 'five-day course of ivermectin for the treatment of COVID-19 may reduce ' 'the duration of illness. Int J Infect Dis. 2021;103:214–6.', 'journal-title': 'Int J Infect Dis.'}, { 'issue': '12', 'key': '756_CR29', 'doi-asserted-by': 'publisher', 'first-page': '828', 'DOI': '10.1016/j.arbres.2020.08.007', 'volume': '56', 'author': 'MSI Khan', 'year': '2020', 'unstructured': 'Khan MSI, Khan MSI, Debnath CR, Nath PN, Al Mahtab M, Nabeka H, et al. ' 'Ivermectin treatment may improve the prognosis of patients with ' 'COVID-19. Arch Bronconeumol. 2020;56(12):828.', 'journal-title': 'Arch Bronconeumol.'}, { 'issue': '1', 'key': '756_CR30', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1186/s12879-021-06104-9', 'volume': '21', 'author': 'N Okumuş', 'year': '2021', 'unstructured': 'Okumuş N, Demirtürk N, Çetinkaya RA, Güner R, Avcı İY, Orhan S, et al. ' 'Evaluation of the effectiveness and safety of adding ivermectin to ' 'treatment in severe COVID-19 patients. BMC Infect Dis. 2021;21(1):1–11.', 'journal-title': 'BMC Infect Dis.'}, { 'key': '756_CR31', 'doi-asserted-by': 'publisher', 'first-page': '462', 'DOI': '10.18433/jpps31457', 'volume': '23', 'author': 'BM Padhy', 'year': '2020', 'unstructured': 'Padhy BM, Mohanty RR, Das S, Meher BR. Therapeutic potential of ' 'ivermectin as add on treatment in COVID 19: a systematic review and ' 'meta-analysis: Ivermectin in COVID-19: A meta-analysis. J Pharm Pharm ' 'Sci. 2020;23:462–9.', 'journal-title': 'J Pharm Pharm Sci.'}, { 'key': '756_CR32', 'doi-asserted-by': 'crossref', 'unstructured': 'Bartoszko JJ, Siemieniuk RA, Kum E, Qasim A, Zeraatkar D, Ge L, et al. ' 'Prophylaxis against covid-19: living systematic review and network ' 'meta-analysis. bmj. 2021:373.', 'DOI': '10.1136/bmj.n949'}, { 'issue': '4', 'key': '756_CR33', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.dsx.2021.102186', 'volume': '15', 'author': 'AFMZ Zein', 'year': '2021', 'unstructured': 'Zein AFMZ, Sulistiyana CS, Raffaelo WM, Pranata R. Ivermectin and ' 'mortality in patients with COVID-19: a systematic review, meta-analysis, ' 'and meta-regression of randomized controlled trials. Diabetes Metab ' 'Syndr. 2021;15(4):102186.', 'journal-title': 'Diabetes Metab Syndr.'}, { 'issue': '4', 'key': '756_CR34', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/MJT.0000000000001402', 'volume': '28', 'author': 'A Bryant', 'year': '2021', 'unstructured': 'Bryant A, Lawrie TA, Dowswell T, Fordham EJ, Mitchell S, Hill SR, et al. ' 'Ivermectin for prevention and treatment of COVID-19 infection: a ' 'systematic review, meta-analysis, and trial sequential analysis to ' 'inform clinical guidelines. Am J Ther. 2021;28(4):e434.', 'journal-title': 'Am J Ther.'}, { 'issue': '12', 'key': '756_CR35', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pmed.1003501', 'volume': '17', 'author': 'MS Kim', 'year': '2020', 'unstructured': 'Kim MS, An MH, Kim WJ, Hwang T-H. Comparative efficacy and safety of ' 'pharmacological interventions for the treatment of COVID-19: a ' 'systematic review and network meta-analysis. PLoS med. ' '2020;17(12):e1003501.', 'journal-title': 'PLoS med.'}, { 'key': '756_CR36', 'doi-asserted-by': 'publisher', 'unstructured': 'Abd-Elsalam S, Noor RA, Badawi R, Khalaf M, Esmail ES, Soliman S, Abd El ' 'Ghafar MS, Elbahnasawy M, Moustafa EF, Hassany SM, Medhat MA, Ramadan ' 'HK, Eldeen MAS, Alboraie M, Cordie A, Esmat G. Clinical study evaluating ' 'the efficacy of ivermectin in COVID-19 treatment: A randomized ' 'controlled study. J Med Virol. 2021;93(10):5833–5838. ' 'https://doi.org/10.1002/jmv.27122.', 'DOI': '10.1002/jmv.27122'}, { 'issue': '14', 'key': '756_CR37', 'doi-asserted-by': 'publisher', 'first-page': '1426', 'DOI': '10.1001/jama.2021.3071', 'volume': '325', 'author': 'E López-Medina', 'year': '2021', 'unstructured': 'López-Medina E, López P, Hurtado IC, Dávalos DM, Ramirez O, Martínez E, ' 'Díazgranados JA, Oñate JM, Chavarriaga H, Herrera S, Parra B, Libreros ' 'G, Jaramillo R, Avendaño AC, Toro DF, Torres M, Lesmes MC, Rios CA, ' 'Caicedo I. Effect oilf ivermectin on time to resolution of symptoms ' 'among adults with md COVID-19: a randomized clinical trial. JAMA. ' '2021;325(14):1426–35. https://doi.org/10.1001/jama.2021.3071.', 'journal-title': 'JAMA.'}, { 'issue': '1', 'key': '756_CR38', 'doi-asserted-by': 'publisher', 'first-page': '635', 'DOI': '10.1186/s12879-021-06348-5', 'volume': '21', 'author': 'J Vallejos', 'year': '2021', 'unstructured': 'Vallejos J, Zoni R, Bangher M, Villamandos S, Bobadilla A, Plano F, ' 'Campias C, Chaparro Campias E, Medina MF, Achinelli F, Guglielmone HA, ' 'Ojeda J, Farizano Salazar D, Andino G, Kawerin P, Dellamea S, Aquino AC, ' 'Flores V, Martemucci CN, Martinez SM, Segovia JE, Reynoso PI, Sosa NC, ' 'Robledo ME, Guarrochena JM, Vernengo MM, Ruiz Diaz N, Meza E, Aguirre ' 'MG. Ivermectin to prevent hospitalizations in patients with COVID-19 ' '(IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial. ' 'BMC Infect Dis. 2021;21(1):635. ' 'https://doi.org/10.1186/s12879-021-06348-5.', 'journal-title': 'BMC Infect Dis.'}, { 'issue': '12', 'key': '756_CR39', 'doi-asserted-by': 'publisher', 'first-page': '1743', 'DOI': '10.1016/j.jiac.2021.08.021', 'volume': '27', 'author': 'A Mohan', 'year': '2021', 'unstructured': 'Mohan A, Tiwari P, Suri TM, Mittal S, Patel A, Jain A, Velpandian T, Das ' 'US, Boppana TK, Pandey RM, Shelke SS, Singh AR, Bhatnagar S, Masih S, ' 'Mahajan S, Dwivedi T, Sahoo B, Pandit A, Bhopale S, Vig S, Gupta R, ' 'Madan K, Hadda V, Gupta N, Garg R, Meena VP, Guleria R. Single-dose oral ' 'ivermectin in mild and moderate COVID-19 (RIVET-COV): A single-centre ' 'randomized, placebo-controlled trial. J Infect Chemother. ' '2021;27(12):1743–9. https://doi.org/10.1016/j.jiac.2021.08.021.', 'journal-title': 'J Infect Chemother.'}, { 'issue': '6', 'key': '756_CR40', 'doi-asserted-by': 'publisher', 'first-page': '989', 'DOI': '10.3390/v13060989', 'volume': '13', 'author': 'AA Samaha', 'year': '2021', 'unstructured': 'Samaha AA, Mouawia H, Fawaz M, Hassan H, Salami A, Bazzal AA, Saab HB, ' 'Al-Wakeel M, Alsaabi A, Chouman M, Moussawi MA, Ayoub H, Raad A, Hajjeh ' 'O, Eid AH, Raad H. 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. Viruses. 2021;13(6):989. ' 'https://doi.org/10.3390/v13060989.', 'journal-title': 'Viruses.'}, { 'issue': '2', 'key': '756_CR41', 'doi-asserted-by': 'publisher', 'first-page': '160', 'DOI': '10.3390/idr14020020', 'volume': '14', 'author': 'JL Beltran Gonzalez', 'year': '2022', 'unstructured': 'Beltran Gonzalez JL, González Gámez M, Mendoza Enciso EA, Esparza ' 'Maldonado RJ, Hernández Palacios D, Dueñas Campos S, Robles IO, Macías ' 'Guzmán MJ, García Díaz AL, Gutiérrez Peña CM, Martinez Medina L, Monroy ' 'Colin VA, Arreola Guerra JM. Efficacy and safety of ivermectin and ' 'Hydroxychloroquine in patients with severe COVID-19: a randomized ' 'controlled trial. Infect Dis Rep. 2022;14(2):160–8. ' 'https://doi.org/10.3390/idr14020020.', 'journal-title': 'Infect Dis Rep'}, { 'key': '756_CR42', 'doi-asserted-by': 'publisher', 'unstructured': 'Krolewiecki A, Lifschitz A, Moragas M, Travacio M, Valentini R, Alonso ' 'DF, et al. Corrigendum to Antiviral effect of high-dose ivermectin in ' 'adults with COVID-19: a proof-of-concept randomized trial. ' 'EClinicalMedicine. 2021;37:100959. ' 'https://doi.org/10.1016/j.eclinm.2021.100959.', 'DOI': '10.1016/j.eclinm.2021.100959'}, { 'key': '756_CR43', 'doi-asserted-by': 'publisher', 'first-page': '733', 'DOI': '10.1016/j.ijid.2022.07.003', 'volume': '122', 'author': 'A Biber', 'year': '2022', 'unstructured': 'Biber A, Harmelin G, Lev D, Ram L, Shaham A, Nemet I, et al. The effect ' 'of ivermectin on the viral load and culture viability in early treatment ' 'of nonhospitalized patients with mild COVID-19 - a double-blind, ' 'randomized placebo-controlled trial. Int J Infect Dis. 2022;122:733–40. ' 'https://doi.org/10.1016/j.ijid.2022.07.003.', 'journal-title': 'Int J Infect Dis.'}, { 'issue': '16', 'key': '756_CR44', 'doi-asserted-by': 'publisher', 'first-page': '1595', 'DOI': '10.1001/jama.2022.18590', 'volume': '328', 'author': 'S Naggie', 'year': '2022', 'unstructured': 'Naggie S, Boulware DR, Lindsell CJ, Stewart TG, Gentile N, Collins S, et ' 'al. Effect of ivermectin vs placebo on time to sustained recovery in ' 'outpatients with mild to moderate COVID-19: a randomized clinical trial. ' 'JAMA. 2022;328(16):1595–603. https://doi.org/10.1001/jama.2022.18590.', 'journal-title': 'JAMA.'}, { 'key': '756_CR45', 'doi-asserted-by': 'publisher', 'unstructured': 'Kerr L, Cadegiani FA, Baldi F, Lobo RB, Assagra WLO, Proença FC, et al. ' 'Corrected: Ivermectin Prophylaxis Used for COVID-19: A Citywide, ' 'Prospective, Observational Study of 223,128 Subjects Using Propensity ' 'Score Matching. Cureus. 2022;14(3):c6. ' 'https://doi.org/10.7759/cureus.c61.', 'DOI': '10.7759/cureus.c61'}], 'container-title': 'GeroScience', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s11357-023-00756-y.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s11357-023-00756-y/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s11357-023-00756-y.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 3, 7]], 'date-time': '2023-03-07T01:08:14Z', 'timestamp': 1678151294000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s11357-023-00756-y'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 3, 7]]}, 'references-count': 45, 'alternative-id': ['756'], 'URL': 'http://dx.doi.org/10.1007/s11357-023-00756-y', 'relation': {}, 'ISSN': ['2509-2715', '2509-2723'], 'subject': ['Geriatrics and Gerontology', 'Aging'], 'container-title-short': 'GeroScience', 'published': {'date-parts': [[2023, 3, 7]]}, 'assertion': [ { 'value': '11 November 2022', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '16 February 2023', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '7 March 2023', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'Not applicable.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Institutional review board statement'}}, { 'value': 'Not applicable.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Informed consent statement'}}, { 'value': 'The authors declare no competing interests.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}]}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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