(Why) are there so few studies of ivermectin as an antiviral in animal models?

Question

I've been trying to understand the ivermectin controversy (especially in view of NIH's recent [partial] change of heart). Based on one of the more recent papers (Jans & Wagstaff) which proposes ivermectin as an antiviral, there are 70+ clinical trials of ivermectin for Covid-19 ongoing.

But what strikes me as odd is that besides a few in vitro research papers mentioned, there's almost a complete dearth of mentions/citations of animal models where ivermectin was successfully used as an antiviral. Contrast this with almost any antiviral for which there are dozens of such animal studies, e.g. for a nearly random example see oseltamivir in this WHO review. So, for ivermectin, as an antiviral, it seems a jump straight from "the test tube" to people.... which seem very unusual, especially since Jans & Wagstaff acknowledge that dosing something as an antiviral is not trivial.

As in many other disciplines, one of the biggest challenges in antiviral research is to transition from laboratory experiments to preclinical/clinical studies, with the question of dosing in the case of ivermectin for viral infectious indications contentious [...]. It is important, firstly, to stress the obvious in this context: that the antiviral activities of ivermectin documented in Table 2 have been derived from laboratory experiments that largely involve high, generally non-physiological, multiplicities of infection, and cell monolayer cultures, often of cell lines such as Vero cells (African green monkey kidney cells impaired in interferon α/β production) that are not clinically relevant.

(In addition, jwatch mentions the same dosing aspect but citing more clear critiques/concerns from three different papers.)

And then Jans & Wagstaff mention (just) one animal trial:

preclinical studies in a lethal Pseudorabies (PRV) mouse challenge model showed that dosing (0.2 mg/kg) 12 h post-infection protected 50% of mice, which could be increased to 60% through administration of ivermectin at the time of infection.

But maybe this paper is just not revealing the full breadth of animal studies for ivermectin as an antiviral, even though there are a lot more of them?

Answer 1

First, we should focus on "ivermectin plus covid19 or a virus that mimics covid19. For now, the FDA recognizes ivermectin as an antiviral drug. Therefore, the comparison should be "antiviral drug + covid19 or covid19-mimicking virus".

The FLCCC may have a bit of a bias because they are enthusiastic proponents of ivermectin, but their report has the following description;

Arevalo et al investigated in a murine model infected with a type 2 family RNA coronavirus similar to SARS-CoV-2, (mouse hepatitis virus), the response to 500 mcg/kg of ivermectin vs. placebo (Arevalo et al., 2020). The study included 40 infected mice, with 20 treated with ivermectin, 20 with phosphate buffered saline, and then 16 uninfected control mice that were also given phosphate buffered saline. At day 5, all the mice were euthanized to obtain tissues for examination and viral load assessment. The 20 non-ivermectin treated infected mice all showed severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while in the ivermectin treated mice a much lower viral load was measured (23,192 AU; p<0.05), with only few livers in the ivermectin treated mice showing histopathological damage such that the differences between the livers from the uninfected control mice were not statistically significant.

Dias De Melo and colleagues recently posted the results of a study they did with golden hamsters that were intranasally inoculated with SARS-CoV-2 virus, and at the time of the infection, the animals also received a single subcutaneous injection of ivermectin at a dose of 0.4mg/kg on day 1 (de Melo et al., 2020). Control animals received only the physiologic solution. They found the following among the ivermectin treated hamsters; a dramatic reduction in anosmia (33.3% vs 83.3%, p=.03) which was also sex-dependent in that the male hamsters exhibited a reduction in clinical score while the treated female hamsters failed to show any sign of anosmia. They also found significant reductions in cytokine concentrations in the nasal turbinate’s and lungs of the treated animals despite the lack of apparent differences in viral titers

Based on this statement, the following two papers seem to fit our purpose. However, it should be noted that these are preprints.

• Arevalo et al
• de Melo et al

Arevalo et al has following description;

However, experimental conditions with SARS-CoV2 are not easily available in research laboratories due to biosecurity reasons, thus having in vivo preclinical data is not always easy.

Isn't this description the answer to your question? If it is clinical research, there is no need to contain infected animals in a laboratory. It must be quite difficult to control a virus that is considered more dangerous than the flu. Also, in the case of influenza, the pharmaceutical companies are probably planning and conducting trials over a long period of time. In contrast, MSD does not seem to be active in the coronary indication of ivermectin.

Answer 2

Ivermectin is already FDA-approved, which means the FDA has decided it had been proven by MERCK to be safe and effective. But only some large cities and regions, smaller countries, and smaller institutions have ruled that it's appropriate or safe and effective for CoViD-19, plus India, which wavers. With around 10,000 people a day dying of CoViD-19, it makes sense to move research forward quickly, as is being done with the vaccines. And ivermectin investigators have moved quickly. There are already results from 96 ivermectin COVID-19 studies available, including 59 peer reviewed, and 59 clinical trials with results comparing treatment and control groups, in homo sapiens. Humans are animals. So reasons including those of Arevalo that @Blue-Various cites, plus the results from the many clinical trials that have run and are ongoing, explain the limited lab animal testing. However I do find 6 lab animal studies, which are identified as such in the 96 ivermectin v. COVID-19 studies I find in the preprint and main literature, which I have listed below, from most recent to oldest. (Fork of; I included all papers/studies excepting the discredited/fraudulent Surgisphere/Desai and López-Medina ones.)

4/29 Ahsan et al., Cureus, doi:10.7759/cureus.14761 (Peer Reviewed) death, ↓50.0%, p=0.03 Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan

4/19 DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2021-001655 (Review) (Peer Reviewed) review Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors

4/17 Loue et al., J. Infectious Diseases and Epidemiology, doi:10.23937/2474-3658/1510202 (Peer Reviewed) death, ↓70.0%, p=0.34 Ivermectin and COVID-19 in Care Home: Case Report

4/16 Morgenstern et al., medRxiv, doi:10.1101/2021.04.10.21255248 (Preprint) hosp., ↓80.0%, p=0.50 Retrospective cohort study of Ivermectin as a SARS-CoV-2 pre-exposure prophylactic method in Healthcare Workers

4/14 Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed) severe case, ↓49.8%, p=0.01 Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial

4/10 Bello et al., Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1911857 (Peer Reviewed) Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets

4/3 Turkia, M., Research Gate (Review) (Preprint) review A timeline of ivermectin-related events in the COVID-19 pandemic

4/1 Mourya et al., Int. J. Health and Clinical Research (Peer Reviewed) viral+, ↓89.4%, p<0.0001 Comparative Analytical Study of Two Different Drug Regimens in Treatment of Covid 19 Positive Patients in Index Medical College Hospital and Research Center, Indore, India

3/30 Wehbe et al., Front. Immunol., doi:10.3389/fimmu.2021.663586 (Review) (Peer Reviewed) review Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities

3/30 Chahla et al., Research Square, doi:10.21203/rs.3.rs-495945/v1 (original preprint 3/30) (Preprint) no disch., ↓86.9%, p=0.004 Cluster Randomised Trials - Ivermectin Repurposing For COVID-19 Treatment Of Outpatients With Mild Disease In Primary Health Care Centers

3/29 Kow et al., Pharmacological Reports, doi:10.1007/s43440-021-00245-z (Peer Reviewed) (meta analysis) meta-analysis The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis

3/26 Tanioka et al., medRxiv, doi:10.1101/2021.03.26.21254377 (Preprint) death, ↓88.2%, p=0.002 Why COVID-19 is not so spread in Africa: How does Ivermectin affect it?

3/25 Udofia et al., Network Modeling Analysis in Health Informatics and Bioinformatics, doi:10.1007/s13721-021-00299-2 (Peer Reviewed) In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV

3/25 Choudhury et al., Future Medicine, doi:10.2217/fvl-2020-0342 (Peer Reviewed) Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach

3/25 Huvemek Press Release (Preprint) no improv., ↓31.6%, p=0.28 Kovid-19 - Huvemek® Phase 2 clinical trial

3/24 Yagisawa et al., The Japanese Journal of Antibiotics, 74-1, Mar 2021 (Review) (Peer Reviewed) review Global trends in clinical studies of ivermectin in COVID-19

3/21 Emmerich et al., Int. J. Environ. Res. Public Health, doi:10.3390/ijerph18073371 (Peer Reviewed) Comparisons between the Neighboring States of Amazonas and Pará in Brazil in the Second Wave of COVID-19 Outbreak and a Possible Role of Early Ambulatory Treatment

3/18 Del Franco et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1008 (Peer Reviewed) Ivermectin in Long-Covid Patients: A Retrospective Study

3/12 Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) recov. time, ↓5.6%, p=0.87 Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study

3/11 Nardelli et al., Signa Vitae, doi:10.22514/sv.2021.043 (Peer Reviewed) (meta analysis) death, ↓79.5%, p<0.0001 Crying wolf in time of Corona: the strange case of ivermectin and hydroxychloroquine. Is the fear of failure withholding potential life-saving treatment from clinical use?

3/11 Scheim et al., OSF Preprints (Preprint) (meta analysis) meta-analysis Ivermectin sales in Valle del Cauca, Colombia, patterns of AEs, and other background re López-Medina et al. 2021

3/11 Bryant et al., Research Square, doi:10.21203/rs.3.rs-317485/v1 (OSF preprints 3/11) (Preprint) (meta analysis) death, ↓68.0%, p=0.006 Ivermectin for prevention and treatment of COVID-19 infection: a systematic review and meta-analysis

3/11 Scheim et al., OSF Preprints (Preprint) (meta analysis) meta-analysis Protocol violations in López-Medina et al.: 38 switched ivermectin (IVM) and placebo doses, failure of blinding, widespread IVM sales OTC in Cali, and nearly identical AEs for the IVM and control groups

3/10 Yesilbag et al., Virus Research, doi:10.1016/j.virusres.2021.198384 (Peer Reviewed) (In Vitro) in vitro Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro

3/9 Pott-Junior et al., Toxicology Reports, doi:10.1016/j.toxrep.2021.03.003 (Peer Reviewed) ventilation, ↓85.2%, p=0.25 Use of ivermectin in the treatment of Covid-19: a pilot trial

3/8 Chamie-Quintero et al., OSF Preprints (Preprint) Ivermectin for COVID-19 in Peru: 14-fold reduction in nationwide excess deaths, p=.002 for effect by state, then 13-fold increase after ivermectin use restricted

3/8 Guzman et al., medRxiv, doi:10.1101/2021.03.04.21252084 (Preprint) Factors associated with increased mortality in critically ill COVID-19 patients in a Mexican public hospital: the other faces of health system oversaturation

3/8 Galan et al., Pathogens and Global Health, doi:10.1080/20477724.2021.1890887 (Peer Reviewed) Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection

3/5 Descotes, J., ImmunoSafe Consultance (Preprint) safety analysis Medical Safety of Ivermectin

3/1 Saha et al., Structural Chemistry, doi:10.1007/s11224-021-01776-0 (preprint 3/1) (Peer Reviewed) The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2

2/23 Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Peer Reviewed) death, ↓14.4%, p=1.00 Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial

2/20 BIRD Meeting 20th February 2021 (News) news BIRD Meeting 20th February 2021

2/16 Elalfy et al., J. Med. Virol., doi:10.1002/jmv.26880 (Peer Reviewed) viral+, ↓86.9%, p<0.0001 Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1

2/15 Behera et al., Research Square, doi:10.21203/rs.3.rs-208785/v1 (Preprint) cases, ↓83.0%, p<0.001 Prophylactic role of ivermectin in SARS-CoV-2 infection among healthcare workers

2/12 Biber et al., medRxiv, doi:10.1101/2021.05.31.21258081 (results 2/12/21) (Preprint) hosp., ↓70.2%, p=0.34 Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19, A double-blind, randomized placebo-controlled trial

2/10 Lima-Morales (Peer Reviewed) death, ↓77.7%, p<0.001 Effectiveness of a multidrug therapy consisting of ivermectin, azithromycin, montelukast and acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico

2/2 Mohan et al., Research Square, doi:10.21203/rs.3.rs-191648/v1 (Preprint) no recov., ↓62.5%, p=0.27 Ivermectin in mild and moderate COVID-19 (RIVET-COV): a randomized, placebo-controlled trial

1/29 Cobos-Campos et al., Clin. Res. Trials, 2021, doi:10.15761/CRT.1000333 (Peer Reviewed) (meta analysis) meta-analysis Potential use of ivermectin for the treatment and profilaxis of SARS-CoV-2 infection: Efficacy of ivermectin for SARS-CoV-2

1/27 Castaneda-Sabogal et al., medRxiv, doi:10.1101/2021.01.26.21250420 (Preprint) (meta analysis) meta-analysis Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis

1/25 Eweas et al., Frontiers in Microbiology, doi:10.3389/fmicb.2020.592908 (Peer Reviewed) Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2

1/23 Errecalde et al., Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017 (Peer Reviewed) animal study Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model

1/21 Chamie-Quintero et al., Preprint, doi:10.2139/ssrn.3765018 (Preprint) Sharp Reductions in COVID-19 Case Fatalities and Excess Deaths in Peru in Close Time Conjunction, State-By-State, with Ivermectin Treatments

1/20 Mody et al., Communications Biology, doi:10.1038/s42003-020-01577-x (Peer Reviewed) (In Vitro) in vitro Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

1/19 Shahbaznejad et al., Clinical Therapeutics, doi:10.1016/j.clinthera.2021.04.007 (partial results available 1/19) (Peer Reviewed) death, ↑197.1%, p=1.00 Effect of ivermectin on COVID-19: A multicenter double-blind randomized controlled clinical trial

1/19 Hill et al., Research Square, doi:10.21203/rs.3.rs-148845/v1 (Preprint) (meta analysis) death, ↓75.0%, p=0.0002 Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection

1/16 Samaha et al., Viruses, doi:10.3390/v13060989 (results 1/16) (Peer Reviewed) hosp., ↓85.7%, p=0.24 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

1/16 Bukhari et al., medRxiv, doi:10.1101/2021.02.02.21250840 (results 1/16) (Preprint) viral+, ↓82.4%, p<0.0001 Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease

1/13 Late, PrEP, PEP Kory et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.643369 (Review) (Peer Reviewed) review Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19

1/12 Okumuş et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06104-9 (preprint 1/12) (Peer Reviewed) death, ↓33.3%, p=0.55 Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Severe COVID-19 Patients

1/11 Chahla et al., medRxiv, doi:10.1101/2021.03.26.21254398 (Preprint) cases, ↓95.2%, p=0.002 A randomized trial - intensive treatment based in ivermectin and iota-carrageenan as pre-exposure prophylaxis for COVID-19 in healthcare agents

1/11 Bousquet-Melou et al., Preprint, doi:10.22541/au.161047848.80388481/v1 (Preprint) dosing study Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients

1/10 Formiga et al., J. Control Release, doi:10.1016/j.jconrel.2020.10.009 (Review) (Peer Reviewed) review Ivermectin: an award-winning drug with expected antiviral activity against COVID-19

1/9 Kirti et al., medRxiv, doi:10.1101/2021.01.05.21249310 (Preprint) death, ↓88.7%, p=0.12 Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized placebo-controlled trial

1/8 Chamie, J. (News) news COVID-19 in Mexico

1/6 Babalola et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcab035 (preprint 1/6) (Peer Reviewed) viral+, ↓63.9%, p=0.11 Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos

1/6 Hirsch et al., Microbiology & Infectious Diseases (Peer Reviewed) Ivermectin as Prophylaxis Against COVID-19 Retrospective Cases Evaluation

1/3 Late, PrEP, PEP Lawrie et al., Preprint (Preprint) (meta analysis) death, ↓83.0%, p<0.0001 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

12/31 Wijaya et al., Cermin Dunia Kedokteran, 47:7 (Peer Reviewed) Ivermectin as a Potential Therapeutic Agent for COVID-19 – case studies

12/31 Madrid et al., Heliyon, doi:10.1016/j.heliyon.2020.e05820 (Peer Reviewed) animal study Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation

12/30 McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) review Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)

12/30 Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 (Peer Reviewed) Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection

12/27 Hill, A., Preprint (Preprint) (meta analysis) meta-analysis Meta-analysis of clinical trials of ivermectin to treat COVID-19 infection

12/24 Jeffreys et al., bioRxiv, doi:10.1101/2020.12.23.424232 (Preprint) (In Vitro) in vitro Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2

12/20 Vallejos et al., Trials, doi:10.1186/s13063-020-04813-1 (Preprint) cases, ↓73.4%, p<0.0001 Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): a structured summary of a study protocol for a randomized controlled trial

12/18 Late, PrEP, PEP Kory et al., FLCCC Alliance (Preprint) (meta analysis) death, ↓69.0%, p<0.0001 Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19

12/15 Alam et al., European Journal ofMedical and Health Sciences, doi:10.24018/ejmed.2020.2.6.599 (Peer Reviewed) cases, ↓90.6%, p<0.0001 Ivermectin as Pre-exposure Prophylaxis for COVID-19 among Healthcare Providers in a Selected Tertiary Hospital in Dhaka – An Observational Study

12/15 Afsar et al., SSRN (Preprint) symptoms, ↓92.2%, p=0.04 Ivermectin Use Associated with Reduced Duration of COVID-19 Febrile Illness in a Community Setting

12/11 Hussain et al., International Journal of Molecular and Immuno Oncology, doi:10.25259/IJMIO_30_2020 (Peer Reviewed) Outcome of ivermectin and doxycycline in cancer patients with COVID-19: A positive experience in Bangladesh

12/7 Chaccour et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720 (preprint 12/7) (Peer Reviewed) symp. prob., ↓52.9%, p<0.05 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

12/4 Kalfas et al., medRxiv, doi:10.1101/2020.11.30.20236570 (Preprint) meta-analysis The therapeutic potential of ivermectin for COVID-19: a systematic review of mechanisms and evidence

12/4 Surnar et al., ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179 (Peer Reviewed) (In Vitro) in vitro Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19

12/2 Ahmed et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.191 (Peer Reviewed) symptoms, ↓85.0%, p=0.09 A five day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness

12/2 Chamie, J. (News) news The effect of using ivermectin to control COVID-19 in Chiapas

12/1 Alonso et al., (Preprint) death, ↓91.8%, p=0.009 COVID-19: Uso de ivermectina

11/28 Bernigaud et al., Annals of Dermatology and Venereology, doi:10.1016/j.annder.2020.09.231 (Peer Reviewed) death, ↓99.4%, p=0.08 Ivermectin benefit: from scabies to COVID-19, an example of serendipity

11/28 Hellwig et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106248 (Peer Reviewed) cases, ↓78.0%, p<0.02 A COVID-19 Prophylaxis? Lower incidence associated with prophylactic administration of Ivermectin

11/24 Niaee et al., Research Square, doi:10.21203/rs.3.rs-109670/v1 (Preprint) death, ↓81.8%, p=0.001 Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial

11/22 de Melo et al., bioRxiv, doi:10.1101/2020.11.21.392639 (Preprint) animal study Anti-COVID-19 efficacy of ivermectin in the golden hamster

11/18 Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223 (Preprint) death, ↓99.1%, p=0.04 Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience

11/17 Carvallo et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1007 (Peer Reviewed) cases, ↓99.9%, p<0.0001 Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel

11/14 Spoorthi et al., IAIM, 2020, 7:10, 177-182 (Peer Reviewed) recov. time, ↓21.1%, p=0.03 Utility of Ivermectin and Doxycycline combination for the treatment of SARSCoV-2

11/11 Camprubí et al., PLoS ONE, 15:11, doi:10.1371/journal.pone.0242184 (Peer Reviewed) ventilation, ↓40.0%, p=0.67 Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients

11/10 Turkia, M., ResearchGate (Review) (Preprint) review FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review

11/4 Cadegiani et al., medRxiv, doi:10.1101/2020.10.31.20223883 (Preprint) death, ↓78.3%, p=0.50 Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients

11/3 Late Morgenstern et al., J. Clinical Trials (preprint 11/3) (Peer Reviewed) The Use of Compassionate Ivermectin in the Management of SymptomaticOutpatients and Hospitalized Patients with Clinical Diagnosis of Covid-19 at theCentro Medico Bournigal and at the Centro Medico Punta Cana, GrupoRescue, Dominican Republic, from May 1 to August 10, 2020

11/3 Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) cases, ↓53.8%, p<0.0001 Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study

11/2 Arévalo et al., Scientific Reports, doi:10.1038/s41598-021-86679-0 (preprint 11/2/20) (Peer Reviewed) animal study Ivermectin reduces in vivo coronavirus infection in a mouse experimental model

10/31 Chang et al., ResearchGate (Preprint) COVID-19: Effectiveness of pre-exposure prophylaxis with ivermectin in exposed persons

10/31 Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed) hosp., ↑13.9%, p=0.45 Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis

10/26 Hashim et al., medRxiv, doi:10.1101/2020.10.26.20219345 (Preprint) death, ↓66.7%, p=0.27 Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-19 patients in Baghdad, Iraq

10/22 Guerrero et al., Colombia Médica, doi:10.25100/cm.v51i4.4613 (Peer Reviewed) COVID-19: The Ivermectin African Enigma

10/19 Carvallo et al., NCT04425850 (Preprint) cases, ↓96.3%, p<0.0001 Usefulness of Topic Ivermectin and Carrageenan to Prevent Contagion of Covid 19 (IVERCAR)

10/13 Chaccour et al., Scientific Reports, doi:10.1038/s41598-020-74084-y (Peer Reviewed) animal study Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats

10/13 Rajter et al., Chest, doi:10.1016/j.chest.2020.10.009 (Peer Reviewed) death, ↓46.0%, p=0.04 Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID-19 (ICON study)

10/9 Mahmud et al., Journal of International Medical Research, doi:10.5061/dryad.qjq2bvqf6 (preprint 10/9/20) (Peer Reviewed) death, ↓85.7%, p=0.25 Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial

10/8 Francés-Monerris et al., ChemRxiv, doi:10.26434/chemrxiv.12782258.v1 (Preprint) (Theory) theory Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent

10/8 Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint) death, ↓17.1%, p=0.01 Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru

9/30 Chachar et al., International Journal of Sciences, 9:31-35, doi:10.18483/ijSci.2378 (Peer Reviewed) no recov., ↓10.0%, p=0.50 Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients

9/24 Khan et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.08.007 (Letter) death, ↓87.0%, p<0.05 Ivermectin treatment may improve the prognosis of patients with COVID-19

9/22 Li et al., J. Cellular Physiology, doi:10.1002/jcp.30055 (Peer Reviewed) (In Vitro) in vitro Quantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment

9/15 Carvallo et al., medRxiv, doi:10.1101/2020.09.10.20191619 (Preprint) death, ↓87.9%, p=0.05 Safety and Efficacy of the combined use of ivermectin, dexamethasone, enoxaparin and aspirin against COVID-19

9/15 Jans et al., Cells 2020, 9:9, 2100, doi:10.3390/cells9092100 (Review) (Letter) review Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?

9/6 DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2020-001350 (Review) (Peer Reviewed) review Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19

9/3 Podder et al., IMC J. Med. Science, 14:2, July 2020 (Peer Reviewed) recov. time, ↓16.1%, p=0.34 Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study

8/31 Kishoria et al., Paripex - Indian Journal of Research, doi:10.36106/paripex/4801859 (Peer Reviewed) no disch., ↑7.5%, p=1.00 Ivermectin as adjuvant to hydroxychloroquine in patients resistant to standard treatment for SARS-CoV-2: results of an open-label randomized clinical study

8/28 Shouman et al., Journal of Clinical and Diagnostic Research, doi:10.7860/JCDR/2020/46795.0000 (Peer Reviewed) symp. case, ↓91.3%, p<0.001 Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt: A Randomised Clinical Trial

8/15 Espitia-Hernandez et al., Biomedical Research, 31:5 (Peer Reviewed) viral+, ↓97.2%, p<0.0001 Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study

8/14 Bhattacharya et al., Int. J. Scientific Research, doi:10.36106/ijsr/7232245 (Peer Reviewed) Observational Study on Clinical Features, Treatment and Outcome of COVID 19 in a tertiary care Centre in India- a retrospective case series

7/31 Vora et al., Indian Journal of Tuberculosis, doi:10.1016/j.ijtb.2020.07.031 (Review) (Peer Reviewed) review White paper on Ivermectin as a potential therapy for COVID-19

7/31 Chang et al., ResearchGate (Preprint) Post-acute or prolonged COVID-19: ivermectin treatment for patients with persistent symptoms or post-acute symptoms

7/31 Chang et al., ResearchGate, doi:10.13140/RG.2.2.34561.48483/2 (Preprint) (Theory) theory COVID-19: Post-exposure prophylaxis with ivermectin in contacts. At Homes, Places of Work, Nursing Homes, Prisons, and Others

7/31 Alam et al., Journal of Bangladesh College of Physicians and Surgeons, doi:10.3329/jbcps.v38i0.47512 (Peer Reviewed) A Case Series of 100 COVID-19 Positive Patients Treated with Combination of Ivermectin and Doxycycline

7/31 Rahman et al., J. Bangladesh Coll. Phys. Surg. 38, 5-9, doi:10.3329/jbcps.v38i0 (Peer Reviewed) Comparison of Viral Clearance between Ivermectin with Doxycycline and Hydroxychloroquine with Azithromycin in COVID-19 Patients

7/14 Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 (Peer Reviewed) hosp., ↓80.6%, p=0.23 A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients

7/8 Gorial et al., medRxiv, doi:10.1101/2020.07.07.20145979 (Preprint) death, ↓71.0%, p=1.00 Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial)

6/19 Lehrer et al., In Vivo, 34:5, 3023-3026, doi:10.21873/invivo.12134 (Theory) theory Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2

6/16 Ramos et al., Preprint (Preprint) Intervención de la Ivermectina Pre-Hospitalaria para la Modificación de la Evolución del Covid19. Estudio realizado en Perú

6/12 Heidary et al., The Journal of Antibiotics, 73, 593–602, doi:10.1038/s41429-020-0336-z (Review) (Peer Reviewed) review Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen

5/2 Chang, G., Research Gate, doi:10.13140/RG.2.2.34689.48482/7 (Preprint) Inclusión de la ivermectina en la primera línea de acción terapéutica para COVID-19

4/21 Bray et al., Antiviral Res., doi:10.1016/j.antiviral.2020.104805 (Review) (Preprint) review Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses

4/3 Caly et al., Antiviral Research, doi:10.1016/j.antiviral.2020.104787 (Peer Reviewed) (In Vitro) in vitro The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro

2013 N/A Guzzo et al., J. Clinical Pharmacology, doi:10.1177/009127002237994 (Peer Reviewed) safety analysis Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects