Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity Score-Matched Retrospective Cohort Study

Morgenstern, Jose; Redondo, Jose N; Olavarria, Alvaro; I, Rondon; Roca, Santiago; Leon, Albida De; Canela, Juan; J, Tavares; Minaya, Miguelina; Lopez, Oscar; Castillo, Ana; Placido, A; Cruz, Rafael Pena; Merette, Yudelka; Francisco, Juan

doi:10.7759/cureus.17455

Cited by 9 publications

(12 citation statements)

References 13 publications

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“…A PrEP com ivermectina foi associada a uma redução estatisticamente significativa na infecção por SARS-CoV-2 e a uma redução de 74% no risco de infecção por COVID-19 (HR 0,26; IC 95% 0,10-0,71). Os autores não encontraram diferença estatisticamente significativa na hospitalização e/ou internação em UTI e no óbito entre os dois grupos (Morgenstern et al, 2021).…”

Section: Discussionunclassified

“…As características dos estudos incluídos nesta revisão sistemática estão resumidas na Tabela 1. Nove artigos foram elegíveis para inclusão no presente estudo, consistindo em quatro ensaios clínicos randomizados (Blum et al, 2021;Chahla et al, 2021;Rocco et al, 2021;Sayed et al, 2021), um ensaio clínico não randomizado (Elalfy et al, 2021), uma coorte retrospectiva (Morgenstern et al, 2021), um estudo transversal (López et al, 2021), uma série de casos (Meneses e um relato de caso (Chérrez-Ojeda et al, 2020). Os artigos são procedentes da Argentina (n = 1) (Chahla et al, 2021), Brasil (n = 2) (Blum et al, 2021;Rocco et al, 2021), Egito (n = 2) (Elalfy et al, 2021;Sayed et al, 2021), Equador (n = 1) (Chérrez-Ojeda et al, 2020), México (n = 2) (López et al, 2021;Meneses Calderón et al, 2020) e República Dominicana (n = 1) (Morgenstern et al, 2021).…”

Section: Fonte: Autores (2022)unclassified

“…Nove artigos foram elegíveis para inclusão no presente estudo, consistindo em quatro ensaios clínicos randomizados (Blum et al, 2021;Chahla et al, 2021;Rocco et al, 2021;Sayed et al, 2021), um ensaio clínico não randomizado (Elalfy et al, 2021), uma coorte retrospectiva (Morgenstern et al, 2021), um estudo transversal (López et al, 2021), uma série de casos (Meneses e um relato de caso (Chérrez-Ojeda et al, 2020). Os artigos são procedentes da Argentina (n = 1) (Chahla et al, 2021), Brasil (n = 2) (Blum et al, 2021;Rocco et al, 2021), Egito (n = 2) (Elalfy et al, 2021;Sayed et al, 2021), Equador (n = 1) (Chérrez-Ojeda et al, 2020), México (n = 2) (López et al, 2021;Meneses Calderón et al, 2020) e República Dominicana (n = 1) (Morgenstern et al, 2021). Research, Society and Development, v. 11, n. 8, e43511831090, Quanto ao uso dos medicamentos, três estudos avaliaram a ivermectina para tratamento ou profilaxia da COVID-19 (Chahla et al, 2021;Elalfy et al, 2021;Morgenstern et al, 2021), sendo que apenas um estudo avaliou seu uso de forma isolada (Morgenstern et al, 2021).…”

Section: Fonte: Autores (2022)unclassified

“…Os artigos são procedentes da Argentina (n = 1) (Chahla et al, 2021), Brasil (n = 2) (Blum et al, 2021;Rocco et al, 2021), Egito (n = 2) (Elalfy et al, 2021;Sayed et al, 2021), Equador (n = 1) (Chérrez-Ojeda et al, 2020), México (n = 2) (López et al, 2021;Meneses Calderón et al, 2020) e República Dominicana (n = 1) (Morgenstern et al, 2021). Research, Society and Development, v. 11, n. 8, e43511831090, Quanto ao uso dos medicamentos, três estudos avaliaram a ivermectina para tratamento ou profilaxia da COVID-19 (Chahla et al, 2021;Elalfy et al, 2021;Morgenstern et al, 2021), sendo que apenas um estudo avaliou seu uso de forma isolada (Morgenstern et al, 2021). Em contrapartida, sete estudos avaliaram o uso da nitazoxanida para tratamento ou profilaxia da doença (Blum et al, 2021;Chérrez-Ojeda et al, 2020;Elalfy et al, 2021;López et al, 2021;Meneses Calderón et al, 2020;Rocco et al, 2021;Sayed et al, 2021), dos quais três consideraram seu uso isolado (Blum et al, 2021;Meneses Calderón et al, 2020;Rocco et al, 2021).…”

Section: Fonte: Autores (2022)unclassified

“…No que diz respeito ao tipo de terapia, apenas dois estudos avaliaram a PrEP para a COVID-19, ambos com o medicamento ivermectina (Chahla et al, 2021;Morgenstern et al, 2021). Atualmente, existem ainda poucos estudos com maior validade e qualidade científica acerca da temática, como ensaios clínicos randomizados duplo-cego.…”

Section: Fonte: Autores (2022)unclassified

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Uso de ivermectina e nitazoxanida para tratamento e profilaxia da COVID-19: Uma revisão sistemática

Santos

Neto²,

Rocha³

et al. 2022

RSD

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Objetivos: Revisar sistematicamente a literatura científica acerca das evidências sobre o uso de ivermectina e nitazoxanida como tratamento e profilaxia para a COVID-19. Metodologia: Esta revisão sistemática foi desenvolvida de acordo com o Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). As bases bibliográficas PubMed, Lilacs e SciELO foram pesquisadas em 14 de outubro de 2021 para identificar estudos que avaliaram o uso de ivermectina e nitazoxanida para tratamento ou profilaxia de casos confirmados ou suspeitos de COVID-19. Resultados: Foram recuperados 105 artigos, dos quais 9 foram incluídos para a revisão final, quatro ensaios clínicos randomizados, um ensaio clínico não randomizado, uma coorte retrospectiva, um estudo transversal, uma série de casos e um relato de caso. A maioria dos estudos eram do Brasil, Egito e México, avaliaram a nitazoxanida e abordaram o tratamento da doença. Conclusões: Não existem evidências científicas suficientemente robustas para apoiar o tratamento e/ou a profilaxia com a ivermectina e nitazoxanida para a COVID-19. Apesar dos resultados encontrados não apontarem um risco aumentado de eventos adversos aos medicamentos analisados, não se deve presumir que seu uso é isento de riscos e estes devem ser usados de maneira racional.

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Section: Discussionunclassified

Section: Fonte: Autores (2022)unclassified

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Uso de ivermectina e nitazoxanida para tratamento e profilaxia da COVID-19: Uma revisão sistemática

Santos

Neto²,

Rocha³

et al. 2022

RSD

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Repurposed drug studies on the primary prevention of SARS-CoV-2 infection during the pandemic: systematic review and meta-analysis

Zhou,

Verweij,

Bijlsma

et al. 2023

BMJ Open Resp Res

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ObjectiveCurrent evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the prevention of laboratory-confirmed SARS-CoV-2 infection and/or COVID-19 among healthy adults.DesignSystematic review.EligibilityQuantitative experimental and observational intervention studies that evaluated the effectiveness of repurposed drugs for the primary prevention of SARS-CoV-2 infection and/or COVID-19 disease.Data sourcePubMed and Embase (1 January 2020–28 September 2022).Risk of biasCochrane Risk of Bias 2.0 and Risk of Bias in Non-Randomised Studies of Interventions tools were applied to assess the quality of studies.Data analysisMeta-analyses for each eligible drug were performed if ≥2 similar study designs were available.ResultsIn all, 65 (25 trials, 40 observational) and 29 publications were eligible for review and meta-analyses, respectively. Most studies pertained to hydroxychloroquine (32), ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) (11), statin (8), and ivermectin (8). In trials, hydroxychloroquine prophylaxis reduced laboratory-confirmed SARS-CoV-2 infection (risk ratio: 0.82 (95% CI 0.74 to 0.90), I2=48%), a result largely driven by one clinical trial (weight: 60.5%). Such beneficial effects were not observed in observational studies, nor for prognostic clinical outcomes. Ivermectin did not significantly reduce the risk of SARS-CoV-2 infection (RR: 0.35 (95% CI 0.10 to 1.26), I2=96%) and findings for clinical outcomes were inconsistent. Neither ACEi or ARB were beneficial in reducing SARS-CoV-2 infection. Most of the evidence from clinical trials was of moderate quality and of lower quality in observational studies.ConclusionsResults from our analysis are insufficient to support an evidence-based repurposed drug policy for SARS-CoV-2 prophylaxis because of inconsistency. In the view of scarce supportive evidence on repurposing drugs for COVID-19, alternative strategies such as immunisation of vulnerable people are warranted to prevent the future waves of infection.PROSPERO registration numberCRD42021292797.

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Patch-clamp studies and cell viability assays suggest a distinct site for viroporin inhibitors on the E protein of SARS-CoV-2

Sedky

Sticht

Breitinger

2023

Virol J

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Background SARS-CoV-2 has caused a worldwide pandemic since December 2019 and the search for pharmaceutical targets against COVID-19 remains an important challenge. Here, we studied the envelope protein E of SARS-CoV and SARS-CoV-2, a highly conserved 75–76 amino acid viroporin that is crucial for virus assembly and release. E protein channels were recombinantly expressed in HEK293 cells, a membrane-directing signal peptide ensured transfer to the plasma membrane. Methods Viroporin channel activity of both E proteins was investigated using patch-clamp electrophysiology in combination with a cell viability assay. We verified inhibition by classical viroporin inhibitors amantadine, rimantadine and 5-(N,N-hexamethylene)-amiloride, and tested four ivermectin derivatives. Results Classical inhibitors showed potent activity in patch-clamp recordings and viability assays. In contrast, ivermectin and milbemycin inhibited the E channel in patch-clamp recordings but displayed only moderate activity on the E protein in the cell viability assay, which is also sensitive to general cytotoxic activity of the tested compounds. Nemadectin and ivermectin aglycon were inactive. All ivermectin derivatives were cytotoxic at concentrations > 5 µM, i.e. below the level required for E protein inhibition. Conclusions This study demonstrates direct inhibition of the SARS-CoV-2 E protein by classical viroporin inhibitors. Ivermectin and milbemycin inhibit the E protein channel but their cytotoxicity argues against clinical application.

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Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity Score-Matched Retrospective Cohort Study

Cited by 9 publications

References 13 publications

Uso de ivermectina e nitazoxanida para tratamento e profilaxia da COVID-19: Uma revisão sistemática

Uso de ivermectina e nitazoxanida para tratamento e profilaxia da COVID-19: Uma revisão sistemática

Repurposed drug studies on the primary prevention of SARS-CoV-2 infection during the pandemic: systematic review and meta-analysis

Patch-clamp studies and cell viability assays suggest a distinct site for viroporin inhibitors on the E protein of SARS-CoV-2

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