Ivermectin for COVID-19: real-time analysis of all 113 studies

Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis) meta-analysis v114 Ivermectin for COVID-19: real-time meta analysis of 63 studies Details • Meta analysis using the most serious outcome reported shows 72% [55‑82%] and 86% [75‑92%] improvement for early treatment and prophylaxis, with similar result.. Details Source PDF

Early, Late, PrEP, PEP

Covid Analysis (Preprint) (meta analysis) Ivermectin for COVID-19: real-time meta analysis of 63 studies • Meta analysis using the most serious outcome reported shows 72% [55‑82%] and 86% [75‑92%] improvement for early treatment and prophylaxis, with similar results after exclusion based sensitivity analysis and restriction to peer-reviewed studies or Randomized Controlled Trials.• Statistically significant improvements are seen for mortality, hospitalization, recovery, cases, and viral clearance. 27 studies show statistically significant improvements in isolation. The probability that an ineffective treatment generated results as positive as the 63 studies is estimated to be 1 in 1 trillion.• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 29% of ivermectin studies show zero events in the treatment arm.• Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. All practical, effective, and safe means should be used. Those denying the efficacy of treatments share responsibility for the increased risk of COVID-19 becoming endemic; and the increased mortality, morbidity, and collateral damage.• The evidence base is much larger and has much lower conflict of interest than typically used to approve drugs.• All data to reproduce this paper and sources are in the appendix. See [Bryant, Hariyanto, Kory, Lawrie, Nardelli] for other meta analyses with similar results confirming efficacy. 00.250.50.7511.251.51.752+Kory et al.69%0.31 [0.20-0.47]Improvement, RR [CI]Bryant et al.62%0.38 [0.19-0.73]Lawrie et al.83%0.17 [0.08-0.35]Nardelli et al.79%0.21 [0.11-0.36]Hariyanto et al.69%0.31 [0.15-0.62]WHO (OR)81%0.19 [0.09-0.36]ivmmeta58%0.42 [0.30-0.59]Ivermectin meta analysis mortality resultsivmmeta.com Sep 5, 2021Lower RiskIncreased Risk

Submit Corrections or Comments In Silico González-Paz et al., Biophysical Chemistry, doi:10.1016/j.bpc.2021.106677 (Peer Reviewed) Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach Details In SIlico analysis of the components of ivermectin (avermectin-B1a and avermectin-B1b), suggesting different and complementary inhibitory activity of each component, with an affinity of avermectin-B1b for viral structures, and of avermect.. Details Source PDF

In Silico

González-Paz et al., Biophysical Chemistry, doi:10.1016/j.bpc.2021.106677 (Peer Reviewed) Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach In SIlico analysis of the components of ivermectin (avermectin-B1a and avermectin-B1b), suggesting different and complementary inhibitory activity of each component, with an affinity of avermectin-B1b for viral structures, and of avermectin-B1a for host structures.

González-Paz et al., 8/19/2021, peer-reviewed, 9 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Meta Neil et al., Research Gate, doi:10.13140/RG.2.2.19703.75680 (Preprint) (meta analysis) meta-analysis Bayesian hypothesis testing and hierarchical modelling of ivermectin effectiveness in treating Covid-19 Details Updated Bayesian analysis of a subset of ivermectin trials showing that there is strong evidence to support a causal link between ivermectin and COVID-19 severity and mortality, and that the result is robust in sensitivity analysis, inclu.. Details Source PDF

Meta

Neil et al., Research Gate, doi:10.13140/RG.2.2.19703.75680 (Preprint) (meta analysis) Bayesian hypothesis testing and hierarchical modelling of ivermectin effectiveness in treating Covid-19 Updated Bayesian analysis of a subset of ivermectin trials showing that there is strong evidence to support a causal link between ivermectin and COVID-19 severity and mortality, and that the result is robust in sensitivity analysis, including exclusion of Elgazzar et al.

Neil et al., 8/18/2021, preprint, 2 authors.

Submit Corrections or Comments In Silico González-Paz et al., Journal of Molecular Liquids, doi:10.1016/j.molliq.2021.117284 (Peer Reviewed) Structural Deformability Induced in Proteins of Potential Interest Associated with COVID-19 by binding of Homologues present in Ivermectin: Comparative Study Based in Elastic Networks Models Details In Silico elastic network model analysis of ivermectin components (avermectin-B1a and avermectin-B1b) providing a biophysical and computational perspective of proposed multi-target activity of ivermectin for COVID-19. Details Source PDF

In Silico

González-Paz et al., Journal of Molecular Liquids, doi:10.1016/j.molliq.2021.117284 (Peer Reviewed) Structural Deformability Induced in Proteins of Potential Interest Associated with COVID-19 by binding of Homologues present in Ivermectin: Comparative Study Based in Elastic Networks Models In Silico elastic network model analysis of ivermectin components (avermectin-B1a and avermectin-B1b) providing a biophysical and computational perspective of proposed multi-target activity of ivermectin for COVID-19.

González-Paz et al., 8/17/2021, peer-reviewed, 9 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Late Elavarasi et al., medRxiv, doi:10.1101/2021.08.10.21261855 (Preprint) death, ↓19.6% , p=0.12 Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India - a cohort study Details Retrospective 2017 hospitalized patients in India, showing lower mortality with ivermectin treatment in unadjusted results. No group details are provided and this result is subject to confounding by indication. Details Source PDF

Late treatment study

Elavarasi et al., medRxiv, doi:10.1101/2021.08.10.21261855 (Preprint) Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India - a cohort study Retrospective 2017 hospitalized patients in India, showing lower mortality with ivermectin treatment in unadjusted results. No group details are provided and this result is subject to confounding by indication.

risk of death, 19.6% lower , RR 0.80, p = 0.12 , treatment 48 of 283 (17.0%), control 311 of 1475 (21.1%), unadjusted.

Elavarasi et al., 8/12/2021, retrospective, India, South Asia, preprint, 26 authors, dosage not specified.

Submit Corrections or Comments N/A Pedroso et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101603 (Peer Reviewed) Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response Details Retrospective 45 healthcare workes in Brazil, showing lower creation of antibodies with multiple doses of ivermectin, which may be expected due to the antiviral activity as demonstrated in multiple studies. Authors appear unaware of these.. Details Source PDF

N/A

Pedroso et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101603 (Peer Reviewed) Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response Retrospective 45 healthcare workes in Brazil, showing lower creation of antibodies with multiple doses of ivermectin, which may be expected due to the antiviral activity as demonstrated in multiple studies. Authors appear unaware of these studies, citing only earlier in vitro research, which they misinterpret to suggest that therapeutic concentrations are not reached (for details on why this is incorrect see [1]). Authors combine no dose and one dose. Clinical outcomes and timing of treatment are not provided.

Pedroso et al., 8/12/2021, peer-reviewed, 11 authors.

Submit Corrections or Comments News La Pampa , Argentina (News) death, ↓27.4% La Pampa expondrá a la comunidad científica los resultados del Programa de Intervención Monitoreado de Ivermectina Details News report on the use of ivermectin in La Pampa, Argentina, showing lower mortality with treatment. Details Source PDF

News

La Pampa , Argentina (News) La Pampa expondrá a la comunidad científica los resultados del Programa de Intervención Monitoreado de Ivermectina News report on the use of ivermectin in La Pampa, Argentina, showing lower mortality with treatment.

risk of death, 27.4% lower , RR 0.73 , treatment 3269, control 18149.

risk of combined death/ICU, 38.0% lower , RR 0.62 , treatment 3269, control 18149.

risk of death, 33.4% lower , RR 0.67 , treatment 3269, control 18149, >40yo.

risk of death, 44.0% lower , RR 0.56 , treatment 3269, control 18149, >40yo including comorbidities.

La Pampa et al., 8/10/2021, retrospective, Argentina, South America, preprint, 1 author, dosage 600μg/kg days 1-5.

Submit Corrections or Comments Review Kow et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001441 (Review) (Peer Reviewed) review Pitfalls in Reporting Sample Size Calculation Across Randomized Controlled Trials Involving Ivermectin for the treatment of COVID-19 Details Review of sample size calculations in ivermectin RCTs, showing that existing RCTs are very underpowered. Details Source PDF

Review

Kow et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001441 (Review) (Peer Reviewed) Pitfalls in Reporting Sample Size Calculation Across Randomized Controlled Trials Involving Ivermectin for the treatment of COVID-19 Review of sample size calculations in ivermectin RCTs, showing that existing RCTs are very underpowered.

Kow et al., 8/6/2021, peer-reviewed, 2 authors.

Submit Corrections or Comments Early Together Trial (News) death, ↓18.0% , p=0.54 Early Treatment of COVID-19 with Repurposed Therapies: The TOGETHER Adaptive Platform Trial Details Preliminary report from the Together Trial showing mortality RR 0.82 [0.44-1.52]. The trial randomization chart suggests major problems and does not match the protocol. Trial week 43, the first week for 3 dose ivermectin, shows ~3x pati.. Details Source PDF

Early treatment study

Together Trial (News) Early Treatment of COVID-19 with Repurposed Therapies: The TOGETHER Adaptive Platform Trial Preliminary report from the Together Trial showing mortality RR 0.82 [0.44-1.52]. The trial randomization chart suggests major problems and does not match the protocol. Trial week 43, the first week for 3 dose ivermectin, shows ~3x patients assigned to ivermectin vs. placebo [1]. Since overall treatment improves over time, and because the distribution of variants continually changes and shows significant differences in outcomes, this invalidates the randomization of the trial. (Confounding by time is common is COVID-19 studies and has often obscured efficacy because more treatment group patients were earlier when overall treatment protocols were significantly worse). Minas Gerais statistics show a period of declining CFR shortly after the time of excess assignment to ivermectin. The total numbers for the ivermectin and placebo groups also do not appear to match the totals in the presentation - reaching the number reported for ivermectin would require including some of the patients assigned to single dose ivermectin. Reaching the placebo number requires including placebo patients from the much earlier ivermectin single dose period, and from the early two week period when zero ivermectin patients were assigned.Treatment delay is currently unknown, however the protocol allows very late inclusion and a companion trial reported mostly late treatment. Overall mortality is high for 18+ outpatients. Results may be impacted by late treatment, poor SOC, and may be specific to local variants [2, 3]. Treatment was administered on an empty stomach, greatly reducing expected tissue concentration and making the effective dose about 1/5th of current clinical practice. The trial was conducted in Minas Gerais, Brazil which had substantial community use of ivermectin [4], and prior use of ivermectin is not listed in the excluson criteria.Time from symptom onset to randomization is specified as within 7 days. However the schedule of study activities specifies treatment administration only one day after randomization, suggesting that treatment was delayed an additional day for all patients.There is an unusual inclusion criteria: "patients with expected hospital stays of This trial uses a soft primary outcome, easily subject to bias and event inflation in both arms (e.g., observe >6 hours independent of indication).Trial design, analysis, and presentation, along with previous public and private statements suggest investigator bias. Design: including very late treatment, additional day before administration, including low-risk patients, operation in a region with high community use, specifying administration on an empty stomach, limiting treatment to 3 days, using soft inclusion criterion and a soft primary outcome, easily subject to bias. Analysis: authors perform analysis excluding events very shortly after randomization for fluvoxamine but not ivermectin, and report viral load results for fluvoxamine but not ivermectin. Presentation: falsely describing positive but not statistically significant effects as "no effect, what so ever"
[5, 6]. Prior statements: [7].There are two published protocols, both are called "version 1", we refer to them as 1A (3/11/21 [8]) and 1B (8/5/21 [9]).1B deletes: - subgroup analysis by treatment delay.
- "Amendments to the protocol, except when necessary to eliminate an immediate danger to participants, should be made only with the prior approval of the steering committee. Each applicable regulatory authority and EC must review and approve the amendments before they are implemented."1B adds: "we hypothesize that younger patients will benefit more than older patients"If you are a trial participant please contact us below. For other issues see: [10, 11].

risk of death, 18.0% lower , RR 0.82, p = 0.54 , treatment 18 of 677 (2.7%), control 22 of 678 (3.2%).

extended ER observation or hospitalization, 9.0% lower , RR 0.91, p = 0.51 , treatment 86 of 677 (12.7%), control 95 of 678 (14.0%).

Together Trial et al., 8/6/2021, Double Blind Randomized Controlled Trial, Brazil, South America, preprint, 1 author, dosage 400μg/kg days 1-3.

Submit Corrections or Comments In Silico Rana et al., Research Square, doi:10.21203/rs.3.rs-755838/v1 (Preprint) A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection Details In silico study showing strong binding affinity of ivermectin and doxycycline for SARS-CoV-2 main protease 3CLpro, and increased binding affinity for the combination of both. Details Source PDF

In Silico

Rana et al., Research Square, doi:10.21203/rs.3.rs-755838/v1 (Preprint) A Computational Study of Ivermectin and Doxycycline Combination Drug Against SARS-CoV-2 Infection In silico study showing strong binding affinity of ivermectin and doxycycline for SARS-CoV-2 main protease 3CLpro, and increased binding affinity for the combination of both.

Rana et al., 8/5/2021, preprint, 3 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Review Santin et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100924 (Review) (Peer Reviewed) review Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19 Details Review concluding that the evidence supports worldwide use of ivermectin for COVID-19, complementary to immunization. Authors note that it is likely non-epitope specific, possibly retaining efficacy with new viral strains. They note that .. Details Source PDF

Review

Santin et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100924 (Review) (Peer Reviewed) Ivermectin: a multifaceted drug of Nobel prize-honored distinction with indicated efficacy against a new global scourge, COVID-19 Review concluding that the evidence supports worldwide use of ivermectin for COVID-19, complementary to immunization. Authors note that it is likely non-epitope specific, possibly retaining efficacy with new viral strains. They note that ivermectin has been safely used with 3.7 billion doses since 1987, is well tolerated even at much greater than standard doses, and has been used without serious AEs in high-dose COVID-19 treatment studies.

Santin et al., 8/3/2021, peer-reviewed, 5 authors.

Submit Corrections or Comments Meta Popp et al., Cochrane Database of Systematic Reviews, doi:10.1002/14651858.CD015017.pub2 (Preprint) (meta analysis) meta-analysis Ivermectin for preventing and treating COVID‐19 Details Outdated very biased retrospective meta analysis selecting a small subset of studies, with a majority of results based on only 1 or 2 studies, showing positive (non-statistically significant) results for 10 of 11 primary outcomes across a.. Details Source PDF

Meta

Popp et al., Cochrane Database of Systematic Reviews, doi:10.1002/14651858.CD015017.pub2 (Preprint) (meta analysis) Ivermectin for preventing and treating COVID‐19 Outdated very biased retrospective meta analysis selecting a small subset of studies, with a majority of results based on only 1 or 2 studies, showing positive (non-statistically significant) results for 10 of 11 primary outcomes across a total of 13 studies.This analysis splits up studies in order to dilute the effects and avoid statistical significance. However, we can consider the probability of 10 of 11 positive effects occurring due to chance for an ineffective treatment, which is very unlikely (0.006), indicating efficacy.The study is entirely retrospective in the current version. The protocol is dated April 20, 2021, and the most recent study included is from March 9, 2021. The protocol was modified after publication in order to include a close to null result (Gonzalez et al. "patients discharged without respiratory deterioration or death at 28 days"), so the current protocol is dated July 28, 2021. The analysis may become partly prospective in the future if the authors do not continue to change the protocol.Authors excluded many studies by requiring results at a specific time, for example mortality, ventilation, etc. required results at exactly 28 days. Authors excluded all prophylaxis studies by requiring results at exactly 14 days.Studies comparing with other medications were excluded, however these studies confirm efficacy of ivermectin. The only case where they could overstate the efficacy of ivermectin is if the other medication was harmful. There is some evidence of this for excessive dosage/very late stage use, however that does not apply to any of the studies here.Studies using combined treatment were excluded, even when it is known that the other components have little or no effect. 3 of 4 RCTs with combined treatment use doxycycline in addition [1].Authors are inconsitent regarding active comparators. They state that hydroxychloroquine “does not work”, yet excluded trials comparing ivermectin to a drug they hold to be inactive. Contrariwise, remdesivir was an acceptable comparator, though in some jurisdictions held to be an effective standard of care [2].Other studies were excluded by requiring PCR confirmation.Authors fail to recognize that Risk of Bias (RoB) domains such as blinding are far less important for the objective outcome of mortality.Bryant et al. note several other issues [3].Cochrane was reputable in the past, but is now controlled by pharmaceutical interests. For example, see the news related to the expulsion of founder Dr. Gøtzsche and the associated mass resignation of board members in protest [4]. For another example of Cochrane bias see [5].Authors report funding from the German Federal Ministry of Education and Research, which may be influenced by [6].Bias due to funding is ignored for both analyzed studies and Cochrane. For Cochrane funders see: [7, 8].The BiRD group gave the following early comment: "Yesterday’s Cochrane review surprisingly doesn’t take a pragmatic approach comparing ivermectin versus no ivermectin, like in the majority of other existing reviews. It uses a granular approach similar to WHO’s and the flawed Roman et al paper, splitting studies up and thereby diluting effects. Consequently, the uncertain conclusions add nothing to the evidence base. A further obfuscation of the evidence on ivermectin and an example of research waste. Funding conflicts of interests of the authors and of the journal concerned should be examined."

Popp et al., 7/28/2021, preprint, 8 authors.

Submit Corrections or Comments Early Ontai et al., medRxiv, doi:10.1101/2021.07.21.21260223 (Preprint) Early multidrug treatment of SARS-CoV-2 (COVID-19) and decreased case fatality rates in Honduras Details Report on the nationwide implementation of multi-drug COVID-19 inpatient and outpatient treatment protocols in Honduras, showing a case fatality rate decrease from 9.33% to 2.97%. No decrease was seen in Mexico, a similar Latin American c.. Details Source PDF

Early treatment study

Ontai et al., medRxiv, doi:10.1101/2021.07.21.21260223 (Preprint) Early multidrug treatment of SARS-CoV-2 (COVID-19) and decreased case fatality rates in Honduras Report on the nationwide implementation of multi-drug COVID-19 inpatient and outpatient treatment protocols in Honduras, showing a case fatality rate decrease from 9.33% to 2.97%. No decrease was seen in Mexico, a similar Latin American country that did not introduce multi-drug treatment protocols at that time. Decreases in COVID-19 case fatality rates in Honduras were associated with both the initial publication of the protocol and a subsequent outreach program. Both inpatient and outpatient protocols include ivermectin as one component.

Ontai et al., 7/25/2021, preprint, 6 authors.

Submit Corrections or Comments News World Ivermectin Day (News) news World Ivermectin Day Details Joint event by 22 worldwide organizations. Details Source PDF

News

World Ivermectin Day (News) World Ivermectin Day Joint event by 22 worldwide organizations.

World Ivermectin Day et al., 7/24/2021, preprint, 1 author.

Submit Corrections or Comments Safety Mansour et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.108004 (Peer Reviewed) safety analysis Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study Details Safety analysis of an inhaled lyophilized ivermectin formulation, showing 127-fold increase in drug solubility, and identifying safe dosage levels in rats. Details Source PDF

Safety

Mansour et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.108004 (Peer Reviewed) Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study Safety analysis of an inhaled lyophilized ivermectin formulation, showing 127-fold increase in drug solubility, and identifying safe dosage levels in rats.

Mansour et al., 7/23/2021, peer-reviewed, 7 authors.

Submit Corrections or Comments News FLCCC Alliance and British Ivermectin Recommendation Development Group (News) news Joint Statement of the FLCCC Alliance and British Ivermectin Recommendation Development Group on Retraction of Early Research on Ivermectin Details News release noting that ivermectin remains effective after excluding Elgazzar et al. Given the large magnitude effects and 61 studies, excluding one study with ~3% of patients does not significantly change the evidence base. Details Source PDF

News

FLCCC Alliance and British Ivermectin Recommendation Development Group (News) Joint Statement of the FLCCC Alliance and British Ivermectin Recommendation Development Group on Retraction of Early Research on Ivermectin News release noting that ivermectin remains effective after excluding Elgazzar et al. Given the large magnitude effects and 61 studies, excluding one study with ~3% of patients does not significantly change the evidence base.

FLCCC et al., 7/16/2021, preprint, 2 authors.

Submit Corrections or Comments Meta Neil et al., ResearchGate, doi:0.13140/RG.2.2.31800.88323 (Preprint) (meta analysis) meta-analysis Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease Details Bayesian analysis of a subset of ivermectin trial data concluding that there is overwhelming evidence to support a causal link between ivermectin, COVID-19 severity, and mortality. Details Source PDF

Meta

Neil et al., ResearchGate, doi:0.13140/RG.2.2.31800.88323 (Preprint) (meta analysis) Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease Bayesian analysis of a subset of ivermectin trial data concluding that there is overwhelming evidence to support a causal link between ivermectin, COVID-19 severity, and mortality.

Neil et al., 7/12/2021, preprint, 2 authors.

Submit Corrections or Comments In Silico Muthusamy et al., Journal of Virology & Antiviral Research (Peer Reviewed) Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein Details In Silico study identifying 32 anti-parisitic compounds effectively inhibiting the RBD of the SARS-CoV-2 spike protein, with ivermectin being one of the top compounds. Details Source PDF

In Silico

Muthusamy et al., Journal of Virology & Antiviral Research (Peer Reviewed) Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the Receptor Binding Domain of SARS-CoV-2 Spike protein In Silico study identifying 32 anti-parisitic compounds effectively inhibiting the RBD of the SARS-CoV-2 spike protein, with ivermectin being one of the top compounds.

Muthusamy et al., 7/8/2021, peer-reviewed, 5 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments News Together Trial (News) news Together Trial removes mortality and adverse event outcomes, and sublingual administration mid-trial Details Together Trial removes mortality and adverse event outcomes, and sublingual administration mid-trial. Details Source PDF

News

Together Trial (News) Together Trial removes mortality and adverse event outcomes, and sublingual administration mid-trial Together Trial removes mortality and adverse event outcomes, and sublingual administration mid-trial.

Together Trial et al., 7/8/2021, preprint, 1 author.

Submit Corrections or Comments Late Hazan et al., medRxiv, doi:10.1101/2021.07.06.21259924 (Preprint) death, ↓85.9% , p=0.04 Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients Details Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatme.. Details Source PDF

Late treatment study

Hazan et al., medRxiv, doi:10.1101/2021.07.06.21259924 (Preprint) Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatment. Two patients declined treatment and both died. This study uses a synthetic control arm.

risk of death, 85.9% lower , RR 0.14, p = 0.04 , continuity correction due to zero event.

risk of hospitalization, 93.3% lower , RR 0.07, p = 0.001 , continuity correction due to zero event.

Hazan et al., 7/7/2021, retrospective, USA, North America, preprint, 7 authors, dosage 12mg days 1, 4, 8, this trial uses multiple treatments in the treatment arm (combined with doxycycline, zinc, vitamin D, vitamin C) - results of individual treatments may vary.

Submit Corrections or Comments News Open Letter , Statement of Concern and Request for Retraction, re: Roman et al. (News) news Open Letter, Statement of Concern and Request for Retraction Details Open letter signed by 40 physicians detailing errors and flaws in the Roman et al. meta analysis, and requesting retraction. Details Source PDF

News

Open Letter , Statement of Concern and Request for Retraction, re: Roman et al. (News) Open Letter, Statement of Concern and Request for Retraction Open letter signed by 40 physicians detailing errors and flaws in the Roman et al. meta analysis, and requesting retraction.

Open Letter et al., 7/3/2021, preprint, 40 authors.

Submit Corrections or Comments Review Adegboro et al., African Journal of Clinical and Experimental Microbiology, doi:10.4314/ajcem.v22i3.2 (Review) (Peer Reviewed) review A review of the anti-viral effects of ivermectin Details Review of the antiviral effects of ivermectin. Details Source PDF

Review

Adegboro et al., African Journal of Clinical and Experimental Microbiology, doi:10.4314/ajcem.v22i3.2 (Review) (Peer Reviewed) A review of the anti-viral effects of ivermectin Review of the antiviral effects of ivermectin.

Adegboro et al., 7/2/2021, peer-reviewed, 4 authors.

Submit Corrections or Comments Early Vallejos et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06348-5 (Peer Reviewed) death, ↑33.5% , p=0.70 Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial Details RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, the trial is underpowered. The trial primarily includes low-risk patients that recover quickly without tr.. Details Source PDF

Early treatment study

Vallejos et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06348-5 (Peer Reviewed) Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, the trial is underpowered. The trial primarily includes low-risk patients that recover quickly without treatment, leaving minimal room for improvement with treatment. 74 patients had symptoms for >= 7 days and more than 25% of patients were hospitalized within 1 day (Figure S2). Among the 7 patients requiring ventilation, authors note that the earlier requirement in the ivermectin group may be due to those patients having higher severity at baseline. However, authors know the answer to this - it is unclear why it is not reported. There were more adverse events in the placebo group than the ivermectin group, suggesting a possible issue with dispensing or non-trial medication usage.Authors pre-specify multivariate analysis but do not present it, claiming "no significant differences in the univariate analysis", however multivariate analysis could significantly change the results. Consider for example if just a few extra patients in the ivermectin group were in severe condition based on baseline SpO2. The lower mean SpO2 in the ivermectin group, and the shorter time to ventilation, are consistent with this being the case. Additionally, there are 14% more male patients in the ivermectin group.An extremely large percentage of patients (55%) were excluded based on ivermectin use in the last 7 days. However, ivermectin may retain efficacy much longer (for example antiparasitic activity may persist for months [1]). A significant number of patients may also misrepresent their prior and future usage - the population is clearly aware of ivermectin, and patients with progressing disease may be motivated to take it, predicting that they are in the control group.There were no serious adverse events. NCT04529525.

risk of death, 33.5% higher , RR 1.33, p = 0.70 , treatment 4 of 250 (1.6%), control 3 of 251 (1.2%), OR converted to RR.

risk of mechanical ventilation, 33.5% higher , RR 1.33, p = 0.70 , treatment 4 of 250 (1.6%), control 3 of 251 (1.2%), OR converted to RR.

risk of hospitalization, 33.0% lower , RR 0.67, p = 0.23 , treatment 14 of 250 (5.6%), control 21 of 251 (8.4%), OR converted to RR.

risk of no virological cure, 5.0% higher , RR 1.05, p = 0.55 , treatment 137 of 250 (54.8%), control 131 of 251 (52.2%), OR converted to RR, day 3.

risk of no virological cure, 26.8% higher , RR 1.27, p = 0.29 , treatment 38 of 250 (15.2%), control 30 of 251 (12.0%), OR converted to RR, day 12.

Vallejos et al., 7/2/2021, Double Blind Randomized Controlled Trial, Argentina, South America, peer-reviewed, 29 authors, dosage 12mg days 1-2, 110kg 24mg.

Submit Corrections or Comments Review Turkia , M., ResearchGate, doi:10.13140/RG.2.2.16973.36326 (Review) (Preprint) review A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021] Details An extension of the ivermectin timeline covering April - June 2021, including WHO's role and funding, Gavi, COVAX, Trusted News Initiative, International Fact-Checking Network, the role of private philantrophy, Frontiers, comparison to th.. Details Source PDF

Review

Turkia , M., ResearchGate, doi:10.13140/RG.2.2.16973.36326 (Review) (Preprint) A Continuation of a Timeline of Ivermectin-Related Events in the COVID-19 Pandemic [June 30, 2021] An extension of the ivermectin timeline covering April - June 2021, including WHO's role and funding, Gavi, COVAX, Trusted News Initiative, International Fact-Checking Network, the role of private philantrophy, Frontiers, comparison to the H1N1 pandemic, new treatment protocols, and causal modeling.

Turkia et al., 6/30/2021, preprint, 1 author.

Submit Corrections or Comments N/A Roman et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab591 (preprint 5/25/21) (Peer Reviewed) (meta analysis) meta-analysis Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials Details Severely flawed meta analysis. An open letter signed by 40 physicians detailing errors and flaws, and requesting retraction, can be found at [1]. See also [2]. The authors state that they have no conflicts of interest on medRxiv, however.. Details Source PDF

N/A

Roman et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab591 (preprint 5/25/21) (Peer Reviewed) (meta analysis) Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials Severely flawed meta analysis. An open letter signed by 40 physicians detailing errors and flaws, and requesting retraction, can be found at [1]. See also [2].The authors state that they have no conflicts of interest on medRxiv, however Dr. Pasupuleti’s affiliation is Cello Health, whose website [3] says that they provide services such as “brand and portfolio commercial strategy for biotech and pharma”, and that their clients are "24 of the top 25 pharmaceutical companies”.Authors cherry-pick to include only 4 studies reporting non-zero mortality and they claim a mortality RR of 1.11 [0.16-7.65]. However, they reported incorrect values for Niaee et al., claiming an RR of 6.51 [2.18-19.45]. The correct RR for Niaee et al. is 0.18 [0.06-0.55] (as below). After correction, their cherry-picked studies show >60% mortality reduction.Similarly, for viral clearance and NCT04392713, they report 20/41 treatment, 18/45 control, whereas the correct day 7 clearance numbers are 37/41 and 20/45 (sum of clearance @72hrs and @7 days), or 17/41 and 2/45 @72 hrs.The duration of hospital stay for Niaee et al. is also incorrectly reported, showing a lower duration for the control group.All of the errors are in one direction - incorrectly reporting lower than actual efficacy for ivermectin. Authors claim to include all RCTs excluding prophylaxis, however they only include 10 of the 24 non-prophylaxis RCTs (28 including prophylaxis). Authors actually reference meta analyses that do include the missing RCTs, so they should be aware of the missing RCTs.The PubMed search strategy provided is syntactically incorrect.For additional errors, see [4]. Also see [5].Only one of these errors has been partially fixed as of 5/29 - the Niaee RR was corrected, but the associated conclusion was not. Other errors have not been corrected. Comments on this article appear to be censored, with zero comments posted as of July 5.

Roman et al., 6/28/2021, peer-reviewed, 6 authors.

Submit Corrections or Comments Review Jagiasi et al., The International Journal of Clinical Practice, doi:10.1111/ijcp.14574 (Review) (Peer Reviewed) review Variation in therapeutic strategies for the management of severe COVID-19 in India- A nationwide cross-sectional survey Details Survey of medication use for severe COVID-19 in India, showing 33% adoption of ivermectin as of January 2021. Details Source PDF

Review

Jagiasi et al., The International Journal of Clinical Practice, doi:10.1111/ijcp.14574 (Review) (Peer Reviewed) Variation in therapeutic strategies for the management of severe COVID-19 in India- A nationwide cross-sectional survey Survey of medication use for severe COVID-19 in India, showing 33% adoption of ivermectin as of January 2021.

Jagiasi et al., 6/25/2021, peer-reviewed, 19 authors.

Submit Corrections or Comments News Misiones Ministry of Public Health (News) news Results from ivermectin use from the Misiones Ministry of Public Health Details News report on ivermectin use in Misiones, Argentina, showing significantly lower hospitalization and mortality, and a dose-dependent effect with improved results for those taking 0.6mg/kg. Details Source PDF

News

Misiones Ministry of Public Health (News) Results from ivermectin use from the Misiones Ministry of Public Health News report on ivermectin use in Misiones, Argentina, showing significantly lower hospitalization and mortality, and a dose-dependent effect with improved results for those taking 0.6mg/kg.

Misiones Ministry of Public Health et al., 6/22/2021, preprint, 1 author.

Submit Corrections or Comments Review Lind et al., Journal of General Internal Medicine, doi:10.1007/s11606-021-06948-6 (Review) (Peer Reviewed) review Increase in Outpatient Ivermectin Dispensing in the US During the COVID-19 Pandemic: A Cross-Sectional Analysis Details CDC analysis of ivermectin prescriptions in the US suggesting that, while national health authority recognition is delayed in that country, many physicians are aware of the efficacy demonstrated in clinical trials. Details Source PDF

Review

Lind et al., Journal of General Internal Medicine, doi:10.1007/s11606-021-06948-6 (Review) (Peer Reviewed) Increase in Outpatient Ivermectin Dispensing in the US During the COVID-19 Pandemic: A Cross-Sectional Analysis CDC analysis of ivermectin prescriptions in the US suggesting that, while national health authority recognition is delayed in that country, many physicians are aware of the efficacy demonstrated in clinical trials.

Lind et al., 6/18/2021, peer-reviewed, 6 authors.

Submit Corrections or Comments Early Krolewiecki et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100959 (Peer Reviewed) ventilation, ↑151.9% , p=1.00 Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial Details Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reductio.. Details Source PDF

Early treatment study

Krolewiecki et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100959 (Peer Reviewed) Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reduction between groups overall, but a significant difference was found in patients with higher median plasma ivermectin levels (72% vs. 42%, p=0.004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r=0.47, p=0.02). NCT004381884. Authors published a corrigendum: [1].

risk of mechanical ventilation, 151.9% higher , RR 2.52, p = 1.00 , treatment 1 of 27 (3.7%), control 0 of 14 (0.0%), continuity correction due to zero event.

risk of disease progression, 3.7% higher , RR 1.04, p = 1.00 , treatment 2 of 27 (7.4%), control 1 of 14 (7.1%).

Krolewiecki et al., 6/18/2021, Randomized Controlled Trial, Argentina, South America, peer-reviewed, 23 authors, dosage 600μg/kg days 1-5.

Submit Corrections or Comments Meta Bryant et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001402 (preprint 3/11/21) (Peer Reviewed) (meta analysis) death, ↓62.0% , p=0.005 Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines Details Systematic review, meta analysis, and trial sequential analysis of 24 RCTs finding mortality RR 0.38 [0.19-0.73]. Details Source PDF

Meta

Bryant et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001402 (preprint 3/11/21) (Peer Reviewed) (meta analysis) Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines Systematic review, meta analysis, and trial sequential analysis of 24 RCTs finding mortality RR 0.38 [0.19-0.73].

risk of death, 62.0% lower , RR 0.38, p = 0.005 .

Bryant et al., 6/17/2021, peer-reviewed, 7 authors.

Submit Corrections or Comments Review Zaidi et al., The Journal of Antibiotics, doi:10.1038/s41429-021-00430-5 (Review) (Peer Reviewed) review The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article Details Extensive review of 20 mechanisms of action of ivermectin for SARS-CoV-2. Details Source PDF

Review

Zaidi et al., The Journal of Antibiotics, doi:10.1038/s41429-021-00430-5 (Review) (Peer Reviewed) The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article Extensive review of 20 mechanisms of action of ivermectin for SARS-CoV-2.

Zaidi et al., 6/15/2021, peer-reviewed, 2 authors.

Submit Corrections or Comments Early Aref et al., International Journal of Nanomedicine, doi:10.2147/IJN.S313093 (Peer Reviewed) recov. time, ↓63.2% , p=0.0001 Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19 Details RCT 114 patients in Egypt, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment. NCT04716569. Details Source PDF

Early treatment study

Aref et al., International Journal of Nanomedicine, doi:10.2147/IJN.S313093 (Peer Reviewed) Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19 RCT 114 patients in Egypt, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment. NCT04716569.

relative duration of fever, 63.2% lower , relative time 0.37, p , treatment 57, control 57.

risk of no virological cure, 78.6% lower , RR 0.21, p = 0.004 , treatment 3 of 57 (5.3%), control 14 of 57 (24.6%).

Aref et al., 6/15/2021, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 7 authors.

Submit Corrections or Comments N/A Hariyanto et al., Reviews In Medical Virology, doi:10.1002/rmv.2265 (Peer Reviewed) (meta analysis) death, ↓69.0% , p=0.001 Ivermectin and outcomes from Covid-19 pneumonia: A systematic review and meta-analysis of randomized clinical trial studies Details Systematic review and meta analysis of 19 RCTs showing mortality RR 0.31 [0.15-0.62]. Details Source PDF

N/A

Hariyanto et al., Reviews In Medical Virology, doi:10.1002/rmv.2265 (Peer Reviewed) (meta analysis) Ivermectin and outcomes from Covid-19 pneumonia: A systematic review and meta-analysis of randomized clinical trial studies Systematic review and meta analysis of 19 RCTs showing mortality RR 0.31 [0.15-0.62].

risk of death, 69.0% lower , RR 0.31, p = 0.001 .

Hariyanto et al., 6/6/2021, peer-reviewed, 5 authors.

Submit Corrections or Comments Review Wang et al., medRxiv, doi:10.1101/2021.06.01.21258147 (Review) (Preprint) review Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19 Details Analysis of the manufacturing cost of several COVID-19 medications, showing a cost of $0.55 per course of ivermectin, including excipients, formulation, tax, and profit. Details Source PDF

Review

Wang et al., medRxiv, doi:10.1101/2021.06.01.21258147 (Review) (Preprint) Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19 Analysis of the manufacturing cost of several COVID-19 medications, showing a cost of $0.55 per course of ivermectin, including excipients, formulation, tax, and profit.

Wang et al., 6/3/2021, preprint, 4 authors.

Submit Corrections or Comments Late Abd-Elsalam et al., Journal of Medical Virology, doi:10.1002/jmv.27122 (Peer Reviewed) death, ↓25.0% , p=0.70 Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study Details RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy th.. Details Source PDF

Late treatment study

Abd-Elsalam et al., Journal of Medical Virology, doi:10.1002/jmv.27122 (Peer Reviewed) Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy than other trials, and recommend increased dosage in future trials. Time from symptom onset is not specified.

risk of death, 25.0% lower , RR 0.75, p = 0.70 , treatment 3 of 82 (3.7%), control 4 of 82 (4.9%), OR converted to RR, logistic regression.

risk of mechanical ventilation, no change , RR 1.00, p = 1.00 , treatment 3 of 82 (3.7%), control 3 of 82 (3.7%).

hospitalization time, 19.6% lower , relative time 0.80, p = 0.09 , treatment 82, control 82.

Abd-Elsalam et al., 6/2/2021, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 16 authors, dosage 12mg days 1-3.

Submit Corrections or Comments PrEPPEP Mondal et al., Journal of the Indian Medical Association, 119:5 (Peer Reviewed) symp. case, ↓87.9% , p=0.006 Prevalence of COVID-19 Infection and Identification of Risk Factors among Asymptomatic Healthcare Workers: A Serosurvey Involving Multiple Hospitals in West Bengal Details Retrospective 1,470 healthcare workers in India, showing significantly lower risk of symptomatic COVID-19 with ivermectin prophylaxis. Details Source PDF

Prophylaxis study

Mondal et al., Journal of the Indian Medical Association, 119:5 (Peer Reviewed) Prevalence of COVID-19 Infection and Identification of Risk Factors among Asymptomatic Healthcare Workers: A Serosurvey Involving Multiple Hospitals in West Bengal Retrospective 1,470 healthcare workers in India, showing significantly lower risk of symptomatic COVID-19 with ivermectin prophylaxis.

risk of symptomatic case, 87.9% lower , RR 0.12, p = 0.006 , treatment 128, control 1342, OR converted to RR, multivariate logistic regression, control prevalence approximated with overall prevalence.

Mondal et al., 5/31/2021, retrospective, India, South Asia, peer-reviewed, 11 authors, dosage not specified.

Submit Corrections or Comments In Vitro Mountain Valley MD (Preprint) (In Vitro) in vitro Mountain Valley MD Receives Successful Results From BSL-4 COVID-19 Clearance Trial on Three Variants Tested With Ivectosol™ Details In Vitro and mouse study with human ACE2 cells, using solubilized ivermectin with Ivectosol™, showing antiviral effect with B.1.1.7, B.1.351, and P.1 variants of SARS-CoV-2. The ability to inject ivermectin potentially reduces the onset .. Details Source PDF

In Vitro

Mountain Valley MD (Preprint) (In Vitro) Mountain Valley MD Receives Successful Results From BSL-4 COVID-19 Clearance Trial on Three Variants Tested With Ivectosol™ In Vitro and mouse study with human ACE2 cells, using solubilized ivermectin with Ivectosol™, showing antiviral effect with B.1.1.7, B.1.351, and P.1 variants of SARS-CoV-2.The ability to inject ivermectin potentially reduces the onset of action from ~6 hours to ~15 minutes, with much lower variability.

Mountain Valley MD et al., 5/18/2021, preprint, 1 author.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments News FLCCC Public Statement (News) news FLCCC Alliance Statement on the Irregular Actions of Public Health Agencies and the Widespread Disinformation Campaign Against Ivermectin Details Analysis of the ivermectin recommendations from WHO and others, and a call to action for all citizens, scientists, and media to counter false information. Whistleblowers can submit anonymous reports and images at the bottom of this page. Details Source PDF

News

FLCCC Public Statement (News) FLCCC Alliance Statement on the Irregular Actions of Public Health Agencies and the Widespread Disinformation Campaign Against Ivermectin Analysis of the ivermectin recommendations from WHO and others, and a call to action for all citizens, scientists, and media to counter false information. Whistleblowers can submit anonymous reports and images at the bottom of this page.

FLCCC et al., 5/12/2021, preprint, 9 authors.

Submit Corrections or Comments Early Faisal et al., The Professional Medical Journal, doi:10.29309/TPMJ/2021.28.05.5867 (Peer Reviewed) no recov., ↓68.4% , p=0.005 Potential use of azithromycin alone and in combination with ivermectin in fighting against the symptoms of COVID-19 Details RCT 100 outpatients in Pakistan, 50 treated with ivermectin, showing faster recovery with ivermectin. All patients received AZ, zinc, vitamin C, vitamin D, and paracetemol. Details of randomization were not provided. No mortality or hospi.. Details Source PDF

Early treatment study

Faisal et al., The Professional Medical Journal, doi:10.29309/TPMJ/2021.28.05.5867 (Peer Reviewed) Potential use of azithromycin alone and in combination with ivermectin in fighting against the symptoms of COVID-19 RCT 100 outpatients in Pakistan, 50 treated with ivermectin, showing faster recovery with ivermectin. All patients received AZ, zinc, vitamin C, vitamin D, and paracetemol. Details of randomization were not provided. No mortality or hospitalization was reported.

risk of no recovery, 68.4% lower , RR 0.32, p = 0.005 , treatment 6 of 50 (12.0%), control 19 of 50 (38.0%), 6-8 days, mid-recovery.

risk of no recovery, 27.3% lower , RR 0.73, p = 0.11 , treatment 24 of 50 (48.0%), control 33 of 50 (66.0%), 3-5 days.

risk of no recovery, 75.0% lower , RR 0.25, p = 0.09 , treatment 2 of 50 (4.0%), control 8 of 50 (16.0%), 9-10 days.

Faisal et al., 5/10/2021, Randomized Controlled Trial, Pakistan, South Asia, peer-reviewed, 3 authors, dosage 12mg days 1-5.

Submit Corrections or Comments In Vitro Zatloukal et al. (News) (In Vitro) news News report on In Vitro results from the research institute of Prof. Zatloukal Details News report on In Vitro results from the research institute of Prof. Zatloukal, showing that "ivermectin was able to reduce virus replication by a factor of 1,000 even at low concentrations". Details Source PDF

In Vitro

Zatloukal et al. (News) (In Vitro) News report on In Vitro results from the research institute of Prof. Zatloukal News report on In Vitro results from the research institute of Prof. Zatloukal, showing that "ivermectin was able to reduce virus replication by a factor of 1,000 even at low concentrations".

Zatloukal et al., 5/5/2021, preprint, 1 author.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments In Silico Qureshi et al., Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1906750 (Peer Reviewed) Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with new implications Details In Silico study showing inhibition of importin-α1 by ivermectin, which disrupts SARS-CoV-2 replication. Details Source PDF

In Silico

Qureshi et al., Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1906750 (Peer Reviewed) Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with new implications In Silico study showing inhibition of importin-α1 by ivermectin, which disrupts SARS-CoV-2 replication.

Qureshi et al., 5/5/2021, peer-reviewed, 6 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Meta Karale et al., medRxiv, doi:10.1101/2021.04.30.21256415 (Preprint) (meta analysis) meta-analysis A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients Details Systematic review and meta analysis with 30 studies included in quantitative analysis, showing mortality OR 0.39 [0.22-0.70]. Subgroup analysis of trials with severity data showed mortality OR 0.10 [0.03-0.33] for mild/moderate cases. Details Source PDF

Meta

Karale et al., medRxiv, doi:10.1101/2021.04.30.21256415 (Preprint) (meta analysis) A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients Systematic review and meta analysis with 30 studies included in quantitative analysis, showing mortality OR 0.39 [0.22-0.70]. Subgroup analysis of trials with severity data showed mortality OR 0.10 [0.03-0.33] for mild/moderate cases.

Karale et al., 5/4/2021, preprint, 12 authors.

Submit Corrections or Comments Early Merino et al., SocArXiv Papers, doi:10.31235/osf.io/r93g4 (Preprint) hosp., ↓74.4% , p Ivermectin and the odds of hospitalization due to COVID-19: evidence from a quasi-experimental analysis based on a public intervention in Mexico City Details Analysis of Mexico City's use of an ivermectin-based medical kit, showing significantly lower hospitalization with use. Authors use logistic-regression models with matched observations, including adjustments for age, sex, COVID severity, .. Details Source PDF

Early treatment study

Merino et al., SocArXiv Papers, doi:10.31235/osf.io/r93g4 (Preprint) Ivermectin and the odds of hospitalization due to COVID-19: evidence from a quasi-experimental analysis based on a public intervention in Mexico City Analysis of Mexico City's use of an ivermectin-based medical kit, showing significantly lower hospitalization with use. Authors use logistic-regression models with matched observations, including adjustments for age, sex, COVID severity, and comorbidities.

risk of hospitalization, 74.4% lower , RR 0.26, p , model 7, same time period, patients receiving kit.

risk of hospitalization, 68.4% lower , RR 0.32, p , model 1, different time periods, administrative rule.

Merino et al., 5/3/2021, retrospective quasi-randomized (patients receiving kit), population-based cohort, Mexico, North America, preprint, 7 authors, dosage 6mg bid days 1-2.

Submit Corrections or Comments Review Kory et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001377 (Review) (Peer Reviewed) review Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 Details Review of ivermectin trials and epidemiological data, concluding that ivermectin is effective for prophylaxis and treatment, and should be globally and systematically deployed in the prevention and treatment of COVID-19. Details Source PDF

Review

Kory et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001377 (Review) (Peer Reviewed) Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 Review of ivermectin trials and epidemiological data, concluding that ivermectin is effective for prophylaxis and treatment, and should be globally and systematically deployed in the prevention and treatment of COVID-19.

Kory et al., 4/30/2021, peer-reviewed, 5 authors.

Submit Corrections or Comments Late 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 Details Retrospective 165 hospitalized patients in Pakistan showing unadjusted lower mortality with combined ivermectin and doxycycline treatment. Details of the ivermectin group compared to other patients are not provided, however ivermectin was.. Details Source PDF

Late treatment study

Ahsan et al., Cureus, doi:10.7759/cureus.14761 (Peer Reviewed) Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan Retrospective 165 hospitalized patients in Pakistan showing unadjusted lower mortality with combined ivermectin and doxycycline treatment. Details of the ivermectin group compared to other patients are not provided, however ivermectin was given to a similar percentage of patients in the mild, moderate, and severe/critical groups (34.5%, 29.1%, and 36.4%), suggesting that ivermectin treatment was not based on severity.

risk of death, 50.0% lower , RR 0.50, p = 0.03 , treatment 17 of 110 (15.5%), control 17 of 55 (30.9%).

Ahsan et al., 4/29/2021, retrospective, Pakistan, South Asia, peer-reviewed, 10 authors, dosage 150μg/kg days 1-2, 150-200µg/kg, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.

Submit Corrections or Comments Review 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 Details Review suggesting that the effectiveness of ivermectin in the cytokine storm phase of COVID-19 may be, at least in part, an anti-inflammatory effect mediated by increased activation of glycine receptors on leukocytes and possibly vascular.. Details Source PDF

Review

DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2021-001655 (Review) (Peer Reviewed) Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors Review suggesting that the effectiveness of ivermectin in the cytokine storm phase of COVID-19 may be, at least in part, an anti-inflammatory effect mediated by increased activation of glycine receptors on leukocytes and possibly vascular endothelium.

DiNicolantonio et al., 4/19/2021, peer-reviewed, 3 authors.

Submit Corrections or Comments Early 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 Details Small quasi-randomized (patient choice) study with 25 PCR+ patients in a nursing home offered ivermectin, of which 10 chose to be treated. The mean age was 83.5 in the treatment group and 81.8 in the control group. There was lower mortali.. Details Source PDF

Early treatment study

Loue et al., J. Infectious Diseases and Epidemiology, doi:10.23937/2474-3658/1510202 (Peer Reviewed) Ivermectin and COVID-19 in Care Home: Case Report Small quasi-randomized (patient choice) study with 25 PCR+ patients in a nursing home offered ivermectin, of which 10 chose to be treated. The mean age was 83.5 in the treatment group and 81.8 in the control group. There was lower mortality and fewer serious cases with treatment.

risk of death, 70.0% lower , RR 0.30, p = 0.34 , treatment 1 of 10 (10.0%), control 5 of 15 (33.3%).

risk of COVID-19 severe case, 55.0% lower , RR 0.45, p = 0.11 , treatment 3 of 10 (30.0%), control 10 of 15 (66.7%).

Loue et al., 4/17/2021, retrospective quasi-randomized (patient choice), France, Europe, peer-reviewed, 2 authors, dosage 200μg/kg single dose.

Submit Corrections or Comments PrEPPEP Morgenstern et al., Cureus, doi:10.7759/cureus.17455 (preprint 4/16/2021) (Peer Reviewed) hosp., ↓80.0% , p=0.50 Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity Score-Matched Retrospective Cohort Study Details Propensity matched retrospective prophylaxis study of healthcare workers in the Dominican Republic showing significantly lower cases with treatment, and no hospitalization with treatment (versus 2 in the PSM matched control group). The ca.. Details Source PDF

Prophylaxis study

Morgenstern et al., Cureus, doi:10.7759/cureus.17455 (preprint 4/16/2021) (Peer Reviewed) Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity Score-Matched Retrospective Cohort Study Propensity matched retrospective prophylaxis study of healthcare workers in the Dominican Republic showing significantly lower cases with treatment, and no hospitalization with treatment (versus 2 in the PSM matched control group). The cases with treatment were mostly in the first week, with only one case in the second and third weeks, and none in the fourth week. There were no severe side effects. In post-hoc analysis, as the treatment group discontinued treatment over time, their protection also decreased. NCT04832945.

risk of hospitalization, 80.0% lower , RR 0.20, p = 0.50 , treatment 0 of 271 (0.0%), control 2 of 271 (0.7%), continuity correction due to zero event, PSM.

risk of COVID-19 case, 74.0% lower , RR 0.26, p = 0.008 , treatment 5 of 271 (1.8%), control 18 of 271 (6.6%), adjusted, PSM, multivariate Cox regression.

Morgenstern et al., 4/16/2021, retrospective, propensity score matching, Dominican Republic, Caribbean, peer-reviewed, 16 authors, dosage 200μg/kg weekly.

Submit Corrections or Comments PrEPPEP 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 Details Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin .. Details Source PDF

Prophylaxis study

Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed) Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C.The ivermectin dosage was low for 42 days prophylaxis - only a single dose of 200µg/kg, with a maximum of 12mg.Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters.There were no hospitalizations and no deaths. NCT04446104.

risk of COVID-19 severe case, 49.8% lower , RR 0.50, p = 0.01 , treatment 32 of 617 (5.2%), control 64 of 619 (10.3%).

risk of COVID-19 case, 5.8% lower , RR 0.94, p = 0.61 , treatment 398 of 617 (64.5%), control 433 of 619 (70.0%), adjusted, OR converted to RR, model 6.

Seet et al., 4/14/2021, Cluster Randomized Controlled Trial, Singapore, Asia, peer-reviewed, 15 authors, dosage 12mg single dose, 200µg/kg, maximum 12mg, this trial compares with another treatment - results may be better when compared to placebo.

Submit Corrections or Comments In Silico 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 Details In Silico analysis finding that the in vitro activity of ivermectin may explained by acting as an inhibitor of importin-α, dimeric 3CLpro, and Nsp9. Details Source PDF

In Silico

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 In Silico analysis finding that the in vitro activity of ivermectin may explained by acting as an inhibitor of importin-α, dimeric 3CLpro, and Nsp9.

Bello et al., 4/10/2021, peer-reviewed, 1 author.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Review Turkia , M., Research Gate (Review) (Preprint) review A timeline of ivermectin-related events in the COVID-19 pandemic Details An extensive timeline of ivermectin-related events from April 2020 to March 2021 including studies, news, health authority decisions, biased news coverage, and censorship. The author concludes that in a broader historical perspective, th.. Details Source PDF

Review

Turkia , M., Research Gate (Review) (Preprint) A timeline of ivermectin-related events in the COVID-19 pandemic An extensive timeline of ivermectin-related events from April 2020 to March 2021 including studies, news, health authority decisions, biased news coverage, and censorship.The author concludes that in a broader historical perspective, the timeline depicts rather dysfunctional societies unable to properly communicate and organize themselves, leading to misallocation of resources and decisions that may have conflicted with elementary ethical considerations, with this behavior rationalized by claiming adherence to mental paradigms that may have poorly matched the situation.

Turkia et al., 4/3/2021, preprint, 1 author.

Submit Corrections or Comments Early Mourya et al., Int. J. Health and Clinical Research (Peer Reviewed) viral+, ↓89.4% , p 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 Details Retrospective 100 patients in India with 50 treated with ivermectin, and SOC for all patients including HCQ+AZ, showing much higher viral clearance with ivermectin. Baseline clinical status was worse in the control group. Time of testing .. Details Source PDF

Early treatment study

Mourya et al., Int. J. Health and Clinical Research (Peer Reviewed) 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 Retrospective 100 patients in India with 50 treated with ivermectin, and SOC for all patients including HCQ+AZ, showing much higher viral clearance with ivermectin. Baseline clinical status was worse in the control group. Time of testing after treatment initiation was longer in the control group (mean 7.24 days versus 5.22 days).

risk of no virological cure, 89.4% lower , RR 0.11, p , treatment 5 of 50 (10.0%), control 47 of 50 (94.0%).

Mourya et al., 4/1/2021, retrospective, India, South Asia, peer-reviewed, 5 authors, dosage 12mg days 1-7.

Submit Corrections or Comments Review 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 Details Review of how ivermectin was identified for use in COVID-19, mechanisms of action, and selected clinical trials. Details Source PDF

Review

Wehbe et al., Front. Immunol., doi:10.3389/fimmu.2021.663586 (Review) (Peer Reviewed) Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities Review of how ivermectin was identified for use in COVID-19, mechanisms of action, and selected clinical trials.

Wehbe et al., 3/30/2021, peer-reviewed, 7 authors.

Submit Corrections or Comments Early 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 Details Cluster RCT outpatients in Argentina showing signficantly faster recovery with ivermectin. There were no deaths. Cluster RCT where outpatients in Tucumán were assigned to the ivermectin group and outpatients from San Miguel de Tucumán and.. Details Source PDF

Early treatment study

Chahla et al., Research Square, doi:10.21203/rs.3.rs-495945/v1 (original preprint 3/30) (Preprint) Cluster Randomised Trials - Ivermectin Repurposing For COVID-19 Treatment Of Outpatients With Mild Disease In Primary Health Care Centers Cluster RCT outpatients in Argentina showing signficantly faster recovery with ivermectin. There were no deaths. Cluster RCT where outpatients in Tucumán were assigned to the ivermectin group and outpatients from San Miguel de Tucumán and Gran San Miguel de Tucumán were assigned to the control group. All comorbidities, percentage of male patients, and age were higher in the ivermectin group, favoring the control group. NCT04784481.

risk of no discharge, 86.9% lower , RR 0.13, p = 0.004 , treatment 2 of 110 (1.8%), control 20 of 144 (13.9%), adjusted, OR converted to RR, logistic regression.

Chahla et al., 3/30/2021, Cluster Randomized Controlled Trial, Argentina, South America, preprint, 9 authors, dosage 24mg days 1, 8, 15, 22.

Submit Corrections or Comments Meta 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 Details Small meta analysis of 6 RCTs showing mortality OR 0.21 [0.11-0.42]. Authors do not include two more recent RCTs with mortality results, 10 other studies with mortality results, and a total of 42 other studies including other outcomes. Au.. Details Source PDF

Meta

Kow et al., Pharmacological Reports, doi:10.1007/s43440-021-00245-z (Peer Reviewed) (meta analysis) The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis Small meta analysis of 6 RCTs showing mortality OR 0.21 [0.11-0.42]. Authors do not include two more recent RCTs with mortality results, 10 other studies with mortality results, and a total of 42 other studies including other outcomes. Authors do not distinguish between studies with very different treatment delays (earlier treatment is more successful).

Kow et al., 3/29/2021, peer-reviewed, 4 authors.

Submit Corrections or Comments PrEPPEP 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? Details Retrospective study of the 31 onchocerciasis-endemic countries using the community-directed treatment with ivermectin (CDTI) and the 22 non-endemic countries in Africa, showing significantly lower mortality per capita in the countries us.. Details Source PDF

Prophylaxis study

Tanioka et al., medRxiv, doi:10.1101/2021.03.26.21254377 (Preprint) Why COVID-19 is not so spread in Africa: How does Ivermectin affect it? Retrospective study of the 31 onchocerciasis-endemic countries using the community-directed treatment with ivermectin (CDTI) and the 22 non-endemic countries in Africa, showing significantly lower mortality per capita in the countries using ivermectin.

risk of death, 88.2% lower , RR 0.12, p = 0.002 , relative mean mortality per million.

Tanioka et al., 3/26/2021, retrospective, ecological study, multiple countries, multiple regions, preprint, 3 authors, dosage 200μg/kg, dose varied, typically 150-200μg/kg.

Submit Corrections or Comments In Silico 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 Details In Silico analysis finding that ivermectin had the highest binding energy against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2. Details Source PDF

In Silico

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 In Silico analysis finding that ivermectin had the highest binding energy against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2.

Udofia et al., 3/25/2021, peer-reviewed, 5 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments In Silico 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 Details In Silico analysis finding that ivermectin has high binding affinity for the SARS-CoV-2 viral spike protein, main protease, replicase, and human TMPRSS2 receptors. Details Source PDF

In Silico

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 In Silico analysis finding that ivermectin has high binding affinity for the SARS-CoV-2 viral spike protein, main protease, replicase, and human TMPRSS2 receptors.

Choudhury et al., 3/25/2021, peer-reviewed, 7 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Late Huvemek Press Release (Preprint) no improv., ↓31.6% , p=0.28 Kovid-19 - Huvemek® Phase 2 clinical trial Details Phase 2 results from a multicenter RCT of hospitalized patients in Bulgaria showing faster viral clearance, greater clinical improvement, and improved biomarkers with treatment. Ivermectin was taken on an empty stomach, potentially reduci.. Details Source PDF

Late treatment study

Huvemek Press Release (Preprint) Kovid-19 - Huvemek® Phase 2 clinical trial Phase 2 results from a multicenter RCT of hospitalized patients in Bulgaria showing faster viral clearance, greater clinical improvement, and improved biomarkers with treatment. Ivermectin was taken on an empty stomach, potentially reducing lung tissue concentration by ~2.5x [1]. Limited data has been reported currently. No serious adverse events were observed. EudraCT 2020-002091-12.

risk of no improvement, 31.6% lower , RR 0.68, p = 0.28 , treatment 13 of 50 (26.0%), control 19 of 50 (38.0%), day 7, patients with improvement on WHO scale.

risk of no improvement, 34.5% lower , RR 0.66, p = 0.07 , treatment 19 of 50 (38.0%), control 29 of 50 (58.0%), day 4, patients with improvement on WHO scale.

Huvemek et al., 3/25/2021, Double Blind Randomized Controlled Trial, Bulgaria, Europe, preprint, 1 author, dosage 400μg/kg days 1-3.

Submit Corrections or Comments Review 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 Details Review of ivermectin for COVID-19. Authors note that Kitasato University's project was expanded in response to the results of Caly et al. which had left questions regarding in vivo therapeutic levels, and the results of those studies were.. Details Source PDF

Review

Yagisawa et al., The Japanese Journal of Antibiotics, 74-1, Mar 2021 (Review) (Peer Reviewed) Global trends in clinical studies of ivermectin in COVID-19 Review of ivermectin for COVID-19. Authors note that Kitasato University's project was expanded in response to the results of Caly et al. which had left questions regarding in vivo therapeutic levels, and the results of those studies were positive. Early in the pandemic, Kitasato University requested Merck to conduct clinical trials in Japan because they have priority for an expansion of ivermectin's indications, however Merck declined.Since large companies have declined to study ivermectin for COVID-19, trials have been mostly doctor-initiated with relatively little funding. Authors discuss these, noting that the physicians involved are enthusiastic about avoiding bias, and strive to treat and prevent COVID-19 witn non-profit motives.Authors discuss the trials, epidemiological data, and inaccurate statements made by certain authorities.Authors note that regulations make it challenging for doctor-initiated trials to enroll many participants in a timely manner.Authors conclude that ivermectin may turn out to be comparable to the benefits achieved from the discovery of penicillin - said to be one of the greatest discoveries of the twentieth century.Authors include the nobel prize winning biochemist who discovered ivermectin, Satoshi Ōmura [1].

Yagisawa et al., 3/24/2021, peer-reviewed, 4 authors.

Submit Corrections or Comments Early Emmerich et al., Int. J. Environ. Res. Public Health, doi:10.3390/ijerph18073371 (Preprint) 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 Details Comparison between the two largest neighboring states in Brazil, Amazonas and Pará, showing more than 5 times lower mortality in Pará during the second wave when the Pará government supported early treatment and Amazonas did not, compared.. Details Source PDF

Early treatment study

Emmerich et al., Int. J. Environ. Res. Public Health, doi:10.3390/ijerph18073371 (Preprint) 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 Comparison between the two largest neighboring states in Brazil, Amazonas and Pará, showing more than 5 times lower mortality in Pará during the second wave when the Pará government supported early treatment and Amazonas did not, compared to similar results in the first wave when treatment protocols were similar.

Emmerich et al., 3/21/2021, preprint, 1 author.

Submit Corrections or Comments Late 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 Details Retrospective 856 patients previously admitted to hospital for COVID-19 in Argentina, finding that ivermectin improved recovery from "long covid" symptoms. Details Source PDF

Late treatment study

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 Retrospective 856 patients previously admitted to hospital for COVID-19 in Argentina, finding that ivermectin improved recovery from "long covid" symptoms.

Del Franco et al., 3/18/2021, peer-reviewed, 3 authors.

Submit Corrections or Comments Early 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 Details Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and .. Details Source PDF

Early treatment study

Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups. Subject to the usual limitation of a database study, very small size, and limited evaluation of patients.

relative time to clinical response of wellbeing, 5.6% lower , relative time 0.94, p = 0.87 , treatment 14, control 15.

Roy et al., 3/12/2021, retrospective, database analysis, India, South Asia, preprint, 5 authors, dosage not specified, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.

Submit Corrections or Comments Meta Nardelli et al., Signa Vitae, doi:10.22514/sv.2021.043 (Peer Reviewed) (meta analysis) death, ↓79.5% , p 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? Details Meta analysis of RCT mortality results showing RR 0.19, p Details Source PDF

Meta

Nardelli et al., Signa Vitae, doi:10.22514/sv.2021.043 (Peer Reviewed) (meta analysis) 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? Meta analysis of RCT mortality results showing RR 0.19, p

risk of death, 79.5% lower , RR 0.21, p , treatment 14 of 703 (2.0%), control 57 of 620 (9.2%), OR converted to RR.

Nardelli et al., 3/11/2021, peer-reviewed, 8 authors.

Submit Corrections or Comments Meta 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 Details Analysis of several issues with López-Medina et al. including the atypical adverse effects in the control arm and population use of ivermectin. Details Source PDF

Meta

Scheim et al., OSF Preprints (Preprint) (meta analysis) Ivermectin sales in Valle del Cauca, Colombia, patterns of AEs, and other background re López-Medina et al. 2021 Analysis of several issues with López-Medina et al. including the atypical adverse effects in the control arm and population use of ivermectin.

Scheim et al., 3/11/2021, preprint, 1 author.

Submit Corrections or Comments Meta 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 Details Report on protocol violations in López-Medina et al. Details Source PDF

Meta

Scheim et al., OSF Preprints (Preprint) (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 Report on protocol violations in López-Medina et al.

Scheim et al., 3/11/2021, preprint, 3 authors.

Submit Corrections or Comments In Vitro 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 Details In Vitro study showing that ivermectin can inhibit infection of bovine respiratory disease viral agents BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM and in a dose-dependent manner. Details Source PDF

In Vitro

Yesilbag et al., Virus Research, doi:10.1016/j.virusres.2021.198384 (Peer Reviewed) (In Vitro) Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro In Vitro study showing that ivermectin can inhibit infection of bovine respiratory disease viral agents BCoV, BPIV-3, BVDV, BRSV and BoHV-1 at the concentrations of 2.5 and 5 μM and in a dose-dependent manner.

Yesilbag et al., 3/10/2021, peer-reviewed, 3 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Late 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 Details Very small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe a.. Details Source PDF

Late treatment study

Pott-Junior et al., Toxicology Reports, doi:10.1016/j.toxrep.2021.03.003 (Peer Reviewed) Use of ivermectin in the treatment of Covid-19: a pilot trial Very small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe and reduces symptoms and viral load, and that the antiviral effect appears to be dose-dependent. NCT04431466.

risk of mechanical ventilation, 85.2% lower , RR 0.15, p = 0.25 , treatment 1 of 27 (3.7%), control 1 of 4 (25.0%).

risk of ICU admission, 85.2% lower , RR 0.15, p = 0.25 , treatment 1 of 27 (3.7%), control 1 of 4 (25.0%).

relative improvement in Ct value, 0.8% lower , RR 0.99, p = 1.00 , treatment 27, control 3.

risk of no virological cure, 11.1% higher , RR 1.11, p = 1.00 , treatment 10 of 27 (37.0%), control 1 of 3 (33.3%).

time to viral-, 16.7% lower , relative time 0.83 , treatment 27, control 3.

Pott-Junior et al., 3/9/2021, Randomized Controlled Trial, Brazil, South America, peer-reviewed, 10 authors, dosage 200μg/kg single dose, dose varies in three arms 100, 200, 400μg/kg.

Submit Corrections or Comments Early 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 Details Analysis of ivermectin use in Peru concluding that ivermectin most likely caused a 14 times reduction in excess deaths in Peru, prior to a 13 times increase after reversal of ivermectin use. Authors conclude that the results strongly sugg.. Details Source PDF

Early treatment study

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 Analysis of ivermectin use in Peru concluding that ivermectin most likely caused a 14 times reduction in excess deaths in Peru, prior to a 13 times increase after reversal of ivermectin use. Authors conclude that the results strongly suggest that ivermectin can complement vaccination. They note that the potential mechanism of action, competitive binding with the SARS-CoV-2 spike protein, is likely to be non-epitope specific, possibly maintaining efficacy against emerging mutant strains.

Chamie-Quintero et al., 3/8/2021, preprint, 3 authors.

Submit Corrections or Comments Late 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 Details Retrospective 196 critically ill patients in Mexico. Patients overlap with the existing RCT by Beltran-Gonzalez (NCT04391127). This preprint shows a larger treated population and greater (non-statistically significant) improvement with iv.. Details Source PDF

Late treatment study

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 Retrospective 196 critically ill patients in Mexico. Patients overlap with the existing RCT by Beltran-Gonzalez (NCT04391127). This preprint shows a larger treated population and greater (non-statistically significant) improvement with ivermectin, RR 0.81 [0.53-1.24].

Guzman et al., 3/8/2021, retrospective, Mexico, North America, preprint, 11 authors.

Submit Corrections or Comments Late 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 Details RCT 168 very late stage severe condition hospitalized patients comparing CQ, HCQ, and ivermectin not showing significant differences. Authors were unable to add a control arm due to ethical issues. Authors claim that "the mortality .. Details Source PDF

Late treatment study

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 RCT 168 very late stage severe condition hospitalized patients comparing CQ, HCQ, and ivermectin not showing significant differences. Authors were unable to add a control arm due to ethical issues.Authors claim that "the mortality rates of the three groups are very similar to historical reports of other studies that used placebo in hospitalized patients", without providing any reference. However [1] shows 43% hospital mortality in the northern region of Brazil, where the study was performed, from which we can estimate the mortality with ivermectin in this study is 47% lower, RR 0.53. Further, the study is restricted to more severe cases, hence the expected mortality may be higher.

Galan et al., 3/8/2021, peer-reviewed, 19 authors.

Submit Corrections or Comments Safety Descotes , J., ImmunoSafe Consultance (Preprint) safety analysis Medical Safety of Ivermectin Details Safety analysis of >350 articles showing that ivermectin has an excellent safety profile. The author notes that "no severe adverse event has been reported in dozens of completed or ongoing studies involving thousands of participants.. Details Source PDF

Safety

Descotes , J., ImmunoSafe Consultance (Preprint) Medical Safety of Ivermectin Safety analysis of >350 articles showing that ivermectin has an excellent safety profile. The author notes that "no severe adverse event has been reported in dozens of completed or ongoing studies involving thousands of participants worldwide to evaluate the efficacy of ivermectin against COVID-19".

Descotes et al., 3/5/2021, preprint.

Submit Corrections or Comments Early López-Medina et al., JAMA, doi:10.1001/jama.2021.3071 (Peer Reviewed) death, ↓66.8% , p=0.50 Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial Details An open letter, signed by >100 physicians, concluding this study is fatally flawed can be found at [1]. Phone survey based RCT with low risk patients, 200 ivermectin and 198 control, showing lower mortality, lower disease progression, lo.. Details Source PDF

Early treatment study

López-Medina et al., JAMA, doi:10.1001/jama.2021.3071 (Peer Reviewed) Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial An open letter, signed by >100 physicians, concluding this study is fatally flawed can be found at [1].Phone survey based RCT with low risk patients, 200 ivermectin and 198 control, showing lower mortality, lower disease progression, lower treatment escalation, and faster resolution of symptoms with treatment, without reaching statistical significance. Authors find the results of this trial alone do not support the use of ivermectin. However the effects are all positive, especially for serious outcomes which are unable to reach statistical significance with the very small number of events in the low risk population.With the low risk patient population, there is little room for improvement with an effective treatment - 59/57% (IVM/control) recovered within the first 2 days to either "no symptoms" or "not hospitalized and no limitation of activities"; 73/69% within 5 days. Less than 3% of all patients ever deteriorated.The primary outcome was changed mid-trial, it was originally clinical deterioration, which is more meaningful, and shows greater benefit. The new outcome of resolution of symptoms includes "not hospitalized and no limitation of activities" as a negative outcome and is not very meaningful in terms of assessing how much treatment reduces serious outcomes. Using this measure could completely invalidate results - for example a treatment that eliminates all COVID-19 symptoms but has a temporary minor adverse event could be seen as worse.Authors state that "preliminary reports of other randomized trials of ivermectin as treatment for COVID-19 with positive results have not yet been published in peer-reviewed journals", however there were actually 8 peer-reviewed RCTs with positive effects published prior to this paper (and 19 total peer-reviewed studies with positive effects).Authors advised taking ivermectin on an empty stomach, reducing lung tissue concentration by ~2.5x [2].76 patients were excluded due to control patients receiving ivermectin. However, there was a similar percentage of adverse events like diarrhea, nausea, and abdominal pain in both treatment and control groups. These are potential non-serious side effects of treatment and suggest that it is possible that many more control patients received some kind of treatment.

Ivermectin was widely used in the population and available OTC at the time of the study. The study protocol only excluded patients with previous ivermectin use within 5 days, however other trials often monitor effects 10+ days after the last dose [3].This study reportedly has an ethical issue whereby participants were told the study drug was "D11AX22" [4]. The editor-in-chief of JAMA initially offered to help with this issue, but later indicated that "JAMA does not review consent forms", however the lead author reportedly confirmed the issue. Therefore this paper may be retracted (JAMA has not indicated their response yet) [5, 6, 7].The study protocol specifically allows "the use of other treatments outside of clinical trials". The paper provides no information on what other treatments were used, but other treatments were commonly used at the time, for example [8]. Additionally, the control group did about 5x better than anticipated for deterioration, also suggesting that the control patients used some kind of treatment. Patients which enroll in such a study may be more likely to learn about and use other treatments, especially since they do not know if they are receiving the study medication.Most data was collected via surveys, without physical examination.The trial protocol lists “the duration of supplemental oxygen” as an outcome but the results for this outcome are missing.The study protocol was amended 4 times. Amendments 2-4 are provided but amendment 1 is missing. Amendment 2 increased the inclusion criteria to within 7 days of onset, including more later stage patients and reducing the expected effectiveness.Grants and/or personal fees, including in some cases during the conduct of the study, were provided by Sanofi Pasteur, GlaxoSmithKline, Janssen, Merck, and Gilead. For more details see [9].Other issues can be found in the comments of the article [10].For other confounding issues see: [11].87% medication adherence. NCT04405843.

risk of death, 66.8% lower , RR 0.33, p = 0.50 , treatment 0 of 200 (0.0%), control 1 of 198 (0.5%), continuity correction due to zero event.

risk of escalation of care, 60.8% lower , RR 0.39, p = 0.10 , treatment 4 of 200 (2.0%), control 10 of 198 (5.1%), OR converted to RR.

risk of escalation of care with post-hoc 34.3% lower , RR 0.66, p = 0.51, treatment 4 of 200 (2.0%), control 6 of 198 (3.0%), OR converted to RR.

risk of deterioration by >= 2 points on an 8-point scale, 43.1% lower , RR 0.57, p = 0.35 , treatment 4 of 200 (2.0%), control 7 of 198 (3.5%), OR converted to RR.

risk of fever post randomization, 24.8% lower , RR 0.75, p = 0.33 , treatment 16 of 200 (8.0%), control 21 of 198 (10.6%), OR converted to RR.

risk of unresolved symptoms at day 21, 15.3% lower , RR 0.85, p = 0.53 , treatment 36 of 200 (18.0%), control 42 of 198 (21.2%), OR converted to RR, Cox proportional-hazard model.

hazard ratio for lack of resolution of symptoms, 6.5% lower , RR 0.93, p = 0.53 , treatment 200, control 198.

relative median time to resolution of symptoms, 16.7% lower , relative time 0.83 , treatment 200, control 198.

López-Medina et al., 3/4/2021, Double Blind Randomized Controlled Trial, Colombia, South America, peer-reviewed, median age 37.0, 19 authors, dosage 300μg/kg days 1-5.

Submit Corrections or Comments In Silico Saha et al., Structural Chemistry, doi:10.1007/s11224-021-01776-0 (preprint 3/1) (Preprint) The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2 Details In SIlico analysis predicting that ivermectin has a large binding affinity for the SARS-CoV-2 spike protein. Three different computer modeling techniques show that ivermectin can inhibit SARS-CoV-2 entrance via hACE2. Details Source PDF

In Silico

Saha et al., Structural Chemistry, doi:10.1007/s11224-021-01776-0 (preprint 3/1) (Preprint) The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2 In SIlico analysis predicting that ivermectin has a large binding affinity for the SARS-CoV-2 spike protein. Three different computer modeling techniques show that ivermectin can inhibit SARS-CoV-2 entrance via hACE2.

Saha et al., 3/1/2021, preprint, 2 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Late Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Preprint) death, ↓14.4% , p=1.00 Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial Details RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 36 low dose ivermectin and 37 control patients not finding significant differences. NCT04391127. Details Source PDF

Late treatment study

Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Preprint) Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 36 low dose ivermectin and 37 control patients not finding significant differences. NCT04391127.

risk of death, 14.4% lower , RR 0.86, p = 1.00 , treatment 5 of 36 (13.9%), control 6 of 37 (16.2%).

risk of respiratory deterioration or death, 8.6% lower , RR 0.91, p = 1.00 , treatment 8 of 36 (22.2%), control 9 of 37 (24.3%).

risk of no hospital discharge, 37.0% higher , RR 1.37, p = 0.71 , treatment 4 of 36 (11.1%), control 3 of 37 (8.1%).

Gonzalez et al., 2/23/2021, Double Blind Randomized Controlled Trial, Mexico, North America, preprint, mean age 53.8, 13 authors, dosage 12mg single dose, 18mg for patients >80kg.

Submit Corrections or Comments News BIRD Meeting 20th February 2021 (News) news BIRD Meeting 20th February 2021 Details The British Ivermectin Recommendation Development (BIRD) panel, with dozens of multi-national scientists & doctors, issued sweeping recommendations for the immediate global use of ivermectin. Details Source PDF

News

BIRD Meeting 20th February 2021 (News) BIRD Meeting 20th February 2021 The British Ivermectin Recommendation Development (BIRD) panel, with dozens of multi-national scientists & doctors, issued sweeping recommendations for the immediate global use of ivermectin.

BIRD et al., 2/20/2021, preprint, 1 author.

Submit Corrections or Comments Early Elalfy et al., J. Med. Virol., doi:10.1002/jmv.26880 (Peer Reviewed) viral+, ↓86.9% , p Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1 Details Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance. Details Source PDF

Early treatment study

Elalfy et al., J. Med. Virol., doi:10.1002/jmv.26880 (Peer Reviewed) Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1 Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.

risk of no virological cure, 86.9% lower , RR 0.13, p , treatment 7 of 62 (11.3%), control 44 of 51 (86.3%), day 15.

risk of no virological cure, 58.1% lower , RR 0.42, p , treatment 26 of 62 (41.9%), control 51 of 51 (100.0%), day 7.

Elalfy et al., 2/16/2021, retrospective, Egypt, Africa, peer-reviewed, 15 authors, dosage 18mg days 1, 4, 7, 10, 13, 120kg 30mg, this trial uses multiple treatments in the treatment arm (combined with nitazoxanide, ribavirin, and zinc) - results of individual treatments may vary.

Submit Corrections or Comments PrEPPEP Behera et al., Cureus 13:8, doi:10.7759/cureus.16897 (preprint 2/15/21) (Peer Reviewed) cases, ↓83.0% , p Prophylactic Role of Ivermectin in Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Workers Details Prospective prophylaxis study with 3,532 healthcare workers, 2,199 receiving two-dose ivermectin prophylaxis, showing adjusted relative risk of confirmed COVID-19 with treatment 0.17 [0.12-0.23] p Details Source PDF

Prophylaxis study

Behera et al., Cureus 13:8, doi:10.7759/cureus.16897 (preprint 2/15/21) (Peer Reviewed) Prophylactic Role of Ivermectin in Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Workers Prospective prophylaxis study with 3,532 healthcare workers, 2,199 receiving two-dose ivermectin prophylaxis, showing adjusted relative risk of confirmed COVID-19 with treatment 0.17 [0.12-0.23] p

risk of COVID-19 case, 83.0% lower , RR 0.17, p , treatment 45 of 2199 (2.0%), control 133 of 1147 (11.6%), two doses.

risk of COVID-19 case, 4.0% higher , RR 1.04, p = 0.85 , treatment 23 of 186 (12.4%), control 133 of 1147 (11.6%), patients only receiving the first dose.

Behera et al., 2/15/2021, prospective, India, South Asia, peer-reviewed, 14 authors, dosage 300μg/kg days 1, 4.

Submit Corrections or Comments Early 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 Details Double blind RCT for mild-moderate COVID-19 outpatients in Israel showing significantly faster reduction in viral load with treatment, and lower hospitalization with treatment. The one treatment hospitalization was a few hours after treat.. Details Source PDF

Early treatment study

Biber et al., medRxiv, doi:10.1101/2021.05.31.21258081 (results 2/12/21) (Preprint) 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 Double blind RCT for mild-moderate COVID-19 outpatients in Israel showing significantly faster reduction in viral load with treatment, and lower hospitalization with treatment. The one treatment hospitalization was a few hours after treatment and the patient improved and was discharged quickly. Authors also examine culture viability on days 2-6, with 13% positive in the ivermectin group vs. 48% in the control group. There were no safety issues. Sheba IRB-7156/20. NCT04429711.

risk of hospitalization, 70.2% lower , RR 0.30, p = 0.34 , treatment 1 of 47 (2.1%), control 3 of 42 (7.1%).

risk of no virological cure, 44.8% lower , RR 0.55, p = 0.04 , treatment 13 of 47 (27.7%), control 21 of 42 (50.0%), adjusted, OR converted to RR, multivariable logistic regression, day 6, Ct>30.

risk of no virological cure, 70.2% lower , RR 0.30, p = 0.14 , treatment 2 of 47 (4.3%), control 6 of 42 (14.3%), day 10, non-infectious samples (Ct>30 or non-viable culture).

risk of no virological cure, 82.1% lower , RR 0.18, p = 0.01 , treatment 2 of 47 (4.3%), control 10 of 42 (23.8%), day 8, non-infectious samples (Ct>30 or non-viable culture).

risk of no virological cure, 75.6% lower , RR 0.24, p = 0.02 , treatment 3 of 47 (6.4%), control 11 of 42 (26.2%), day 6, non-infectious samples (Ct>30 or non-viable culture).

risk of no virological cure, 65.1% lower , RR 0.35, p = 0.05 , treatment 4 of 28 (14.3%), control 9 of 22 (40.9%), day 4, non-infectious samples (Ct>30 or non-viable culture).

risk of no virological cure, 51.9% lower , RR 0.48, p = 0.08 , treatment 7 of 47 (14.9%), control 13 of 42 (31.0%), day 10, Ct>30.

risk of no virological cure, 57.9% lower , RR 0.42, p = 0.02 , treatment 8 of 47 (17.0%), control 17 of 42 (40.5%), day 8, Ct>30.

risk of no virological cure, 44.7% lower , RR 0.55, p = 0.05 , treatment 13 of 47 (27.7%), control 21 of 42 (50.0%), day 6, Ct>30.

risk of no virological cure, 31.9% lower , RR 0.68, p = 0.16 , treatment 13 of 28 (46.4%), control 15 of 22 (68.2%), day 4, Ct>30.

Biber et al., 2/12/2021, Double Blind Randomized Controlled Trial, Israel, Middle East, preprint, 10 authors, dosage 12mg days 1-3, 15mg for patients >= 70kg.

Submit Corrections or Comments Late Lima-Morales (Peer Reviewed) death, ↓77.7% , p 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 Details Prospective trial of 768 COVID-19 outpatients in Mexico, 481 treated with ivermectin, AZ, montelukast, and aspirin, and 287 control patients with various treatments, showing significantly lower mortality and hospitalization, and significa.. Details Source PDF

Late treatment study

Lima-Morales (Peer Reviewed) 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 Prospective trial of 768 COVID-19 outpatients in Mexico, 481 treated with ivermectin, AZ, montelukast, and aspirin, and 287 control patients with various treatments, showing significantly lower mortality and hospitalization, and significantly higher recovery at 14 days with treatment.

risk of death, 77.7% lower , RR 0.22, p , treatment 15 of 481 (3.1%), control 52 of 287 (18.1%), adjusted, OR converted to RR, multivariate.

risk of hospitalization, 67.4% lower , RR 0.33, p , treatment 44 of 481 (9.1%), control 89 of 287 (31.0%), adjusted, OR converted to RR, multivariate.

risk of no recovery, 58.6% lower , RR 0.41, p , treatment 75 of 481 (15.6%), control 118 of 287 (41.1%), adjusted, OR converted to RR, recovery at day 14 after symptoms, multivariate.

Lima-Morales et al., 2/10/2021, prospective, Mexico, North America, peer-reviewed, 9 authors, dosage 12mg single dose, this trial uses multiple treatments in the treatment arm (combined with azithromycin, montelukast, and aspirin) - results of individual treatments may vary.

Submit Corrections or Comments Early Mohan et al., Journal of Infection and Chemotherapy, doi:10.1016/j.jiac.2021.08.021 (preprint 2/2/2021) (Peer Reviewed) no recov., ↓62.5% , p=0.27 Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): a single-centre randomized, placebo-controlled trial Details RCT in India with low risk patients, comparing 24mg ivermectin, 12mg ivermectin, and placebo showing non-statistically significant improvements in recovery and PCR+ status (day 5 both arms, day 7 24mg only) with treatment, and showing gre.. Details Source PDF

Early treatment study

Mohan et al., Journal of Infection and Chemotherapy, doi:10.1016/j.jiac.2021.08.021 (preprint 2/2/2021) (Peer Reviewed) Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): a single-centre randomized, placebo-controlled trial RCT in India with low risk patients, comparing 24mg ivermectin, 12mg ivermectin, and placebo showing non-statistically significant improvements in recovery and PCR+ status (day 5 both arms, day 7 24mg only) with treatment, and showing greater improvement for the higher dose arm. Viral load decline was similar in all arms. There were no deaths or use of mechanical ventilation. There were no serious adverse events. Note that our pre-specified protocol prioritizes clinical outcomes over PCR results. The supplementary appendix is not currently available.

risk of no discharge at day 14, 62.5% lower , RR 0.38, p = 0.27 , treatment 2 of 40 (5.0%), control 6 of 45 (13.3%), ivermectin 24mg.

risk of no discharge at day 14, 43.8% lower , RR 0.56, p = 0.49 , treatment 3 of 40 (7.5%), control 6 of 45 (13.3%), ivermectin 12mg.

risk of clinical worsening, 32.5% lower , RR 0.68, p = 0.72 , treatment 3 of 40 (7.5%), control 5 of 45 (11.1%), ivermectin 24mg.

risk of clinical worsening, 55.0% lower , RR 0.45, p = 0.44 , treatment 2 of 40 (5.0%), control 5 of 45 (11.1%), ivermectin 12mg.

risk of no virological cure, 23.8% lower , RR 0.76, p = 0.18 , treatment 21 of 40 (52.5%), control 31 of 45 (68.9%), ivermectin 24mg, day 5.

risk of no virological cure, 5.6% lower , RR 0.94, p = 0.82 , treatment 26 of 40 (65.0%), control 31 of 45 (68.9%), ivermectin 12mg, day 5.

risk of no virological cure, 10.3% lower , RR 0.90, p = 0.65 , treatment 20 of 36 (55.6%), control 26 of 42 (61.9%), ivermectin 24mg, day 7.

risk of no virological cure, 3.2% higher , RR 1.03, p = 1.00 , treatment 23 of 36 (63.9%), control 26 of 42 (61.9%), ivermectin 12mg, day 7.

Mohan et al., 2/2/2021, Double Blind Randomized Controlled Trial, India, South Asia, peer-reviewed, 27 authors, dosage 400μg/kg single dose, 200μg/kg also tested.

Submit Corrections or Comments Meta 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 Details Review finding that there appears to be sufficient evidence to recommend ivermectin for the treatment of COVID-19, especially in the early stages of the disease. Details Source PDF

Meta

Cobos-Campos et al., Clin. Res. Trials, 2021, doi:10.15761/CRT.1000333 (Peer Reviewed) (meta analysis) Potential use of ivermectin for the treatment and profilaxis of SARS-CoV-2 infection: Efficacy of ivermectin for SARS-CoV-2 Review finding that there appears to be sufficient evidence to recommend ivermectin for the treatment of COVID-19, especially in the early stages of the disease.

Cobos-Campos et al., 1/29/2021, peer-reviewed, 9 authors.

Submit Corrections or Comments Meta 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 Details Student-written meta analysis of a very small subset of studies exhibiting very high bias and significant flaws. Some of the problems: - As of the publication date, there are 35 studies, authors include only 4. (They list 5, but two are .. Details Source PDF

Meta

Castaneda-Sabogal et al., medRxiv, doi:10.1101/2021.01.26.21250420 (Preprint) (meta analysis) Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis Student-written meta analysis of a very small subset of studies exhibiting very high bias and significant flaws. Some of the problems:- As of the publication date, there are 35 studies, authors include only 4. (They list 5, but two are the same study, preprint and published version).- From the 17 RCTs, authors include 0.- Authors include only late treatment studies, excluding all 10 early treatment studies and all 10 prophylaxis studies.- Authors did not locate 13 studies, despite this being trivial from existing meta analyses.- There is no logic in the exclusion reasons. For example, they include the most biased study to date, Soto-Becerra, and assign the highest weight to it.- Authors randomly exclude letters but include preprints (excluding letters to help avoid positive results, including preprints to include Soto-Becerra).- Soto-Becerra has clear evidence of extreme bias. The study presents 30 day results and extended KM curves up to day 43 for ivermectin. At 30 days the result is negative but reverts (as do all treatments in the study) and becomes positive before day 43. Authors of this meta analysis ignore the extended followup. Soto-Becerra is a database analysis that includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. More than the total excess mortality happened on the first day. This is consistent with treated patients being in more serious condition, and with many of the control group patients being in hospital for something unrelated to COVID-19. Authors use a machine learning based propensity scoring system that appears over-parameterized and likely to result in significant overfitting and inaccurate results. Essentially they test for all interactions between two and three covariates. The nature and large number of covariates means many random correlations may be found. COVID-19 severity is not used. In summary, this is the lowest quality ivermectin study to date. This study also does not compare treatments with a control group not receiving the treatment - authors put patients receiving treatments after 48 hours in the control group. Authors also state that outcomes within 24 hours were excluded, however KM curves show significant mortality at day 1 (only for the treatment groups).- We checked the reported results for the mortality outcome and found they do not appear to match the actual papers.- Rajter: authors list mortality as 13/85 (treatment), 24/74 (control), the paper shows (for the matched cohort) 13/98 (treatment), 24/98 (control). The adjusted result in the paper is OR 0.27 [0.09-0.80] (multivariate) or OR 0.47 [0.22-0.99] (PSM). These correspond to RR 0.33 and 0.54 respectively, or logRR -1.1 and -0.62. However authors here show logRR 0.54 and 0.85 - they include the study twice (preprint and published). The preprint and published papers have the same multivariate result, the PSM result was added in the published paper. Neither of the two results the authors use match the actual results.- Khan: the paper shows RR 0.13, logRR -2.0. Authors show logRR 0.13.- Soto-Becerra at day 30 shows wHR 1.39 [0.88-2.22], and day 43 weighted KM 0.82 [0.76-0.88]. These correspond to logRR 0.33 and -0.19. Authors show logRR 1.75.- Gorial: there is zero mortality with treatment in this paper. Using the typical continuity correction, the paper shows RR 0.29 when accounting for the different group sizes, or 0.86 when using naive continuity correction that does not account for the very different group sizes. These correspond to logRR -1.24 or -0.15. Authors show logRR 0.60.- Authors did not locate and reference the existing widely known meta-analyses from well-known researchers - Kory et al., Hill et al., Lawrie et al.For more issues see: [1, 2]Authors on Twitter: [3, 4, 5, 6]

Castaneda-Sabogal et al., 1/27/2021, preprint.

Submit Corrections or Comments In Silico 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 Details Molecular docking analysis showing that ivermectin efficiently binds to the viral S protein as well as the human cell surface receptors ACE-2 and TMPRSS2; therefore, it might be involved in inhibiting the entry of the virus into the host .. Details Source PDF

In Silico

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 Molecular docking analysis showing that ivermectin efficiently binds to the viral S protein as well as the human cell surface receptors ACE-2 and TMPRSS2; therefore, it might be involved in inhibiting the entry of the virus into the host cell. It also binds to Mpro and PLpro of SARS-CoV-2; therefore, it might play a role in preventing the post-translational processing of viral polyproteins. The highly efficient binding of ivermectin to the viral N phosphoprotein and nsp14 is suggestive of its role in inhibiting viral replication and assembly.

Eweas et al., 1/25/2021, peer-reviewed, 3 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Animal 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 Details Animal study of a novel spray formulation of ivermectin, showing an advantage of the spray formulation in terms of fast attainment of high and persistent ivermectin concentrations in nasopharyngeal tissue. Details Source PDF

Animal study

Errecalde et al., Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017 (Peer Reviewed) Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model Animal study of a novel spray formulation of ivermectin, showing an advantage of the spray formulation in terms of fast attainment of high and persistent ivermectin concentrations in nasopharyngeal tissue.

Errecalde et al., 1/23/2021, peer-reviewed, 15 authors.

Submit Corrections or Comments Early 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 Details Analysis of ivermectin usage within states in Peru showing sharp reductions in COVID-19 deaths corresponding to the usage of ivermectin treatment. Details Source PDF

Early treatment study

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 Analysis of ivermectin usage within states in Peru showing sharp reductions in COVID-19 deaths corresponding to the usage of ivermectin treatment.

Chamie-Quintero et al., 1/21/2021, preprint, 3 authors.

Submit Corrections or Comments In Vitro 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 Details Computational molecular modeling screening and in vitro analysis for inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme, showing that ivermectin blocked more than 85% of 3CLpro activity of SARS-CoV-2. Antiviral activity of ivermectin.. Details Source PDF

In Vitro

Mody et al., Communications Biology, doi:10.1038/s42003-020-01577-x (Peer Reviewed) (In Vitro) Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents Computational molecular modeling screening and in vitro analysis for inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme, showing that ivermectin blocked more than 85% of 3CLpro activity of SARS-CoV-2. Antiviral activity of ivermectin mediated through the blocking of α/β1 importin has been previously established, this analysis suggests an additional antiviral mechanism of ivermectin for SARS-CoV-2 via inhibitory effects on 3CLpro.

Mody et al., 1/20/2021, peer-reviewed, 9 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Late 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 Details RCT in Iran showing shorter time to recovery and shorter hospitalization time with ivermectin. There were no adverse effects. There was one death in the treatment group, the patient was in critical condition at baseline and died within 24.. Details Source PDF

Late treatment study

Shahbaznejad et al., Clinical Therapeutics, doi:10.1016/j.clinthera.2021.04.007 (partial results available 1/19) (Peer Reviewed) Effect of ivermectin on COVID-19: A multicenter double-blind randomized controlled clinical trial RCT in Iran showing shorter time to recovery and shorter hospitalization time with ivermectin. There were no adverse effects. There was one death in the treatment group, the patient was in critical condition at baseline and died within 24 hours of admission. IRCT20111224008507N3. Also see [1] and the author response [2].

risk of death, 197.1% higher , RR 2.97, p = 1.00 , treatment 1 of 35 (2.9%), control 0 of 34 (0.0%), continuity correction due to zero event, patient died within 24 hours of admission.

risk of mechanical ventilation, 94.3% higher , RR 1.94, p = 1.00 , treatment 2 of 35 (5.7%), control 1 of 34 (2.9%).

recovery time, 31.6% lower , relative time 0.68, p = 0.05 , treatment 35, control 34, duration of dsypnea.

recovery time, 19.2% lower , relative time 0.81, p = 0.02 , treatment 35, control 34, duration of all symptoms.

hospitalization time, 15.5% lower , relative time 0.85, p = 0.02 , treatment 35, control 34.

Shahbaznejad et al., 1/19/2021, Double Blind Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 8 authors, dosage 200μg/kg single dose.

Submit Corrections or Comments Meta 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 Details Meta analysis of 18 ivermectin RCTs with 2,282 patients showing faster viral clearance (dose and duration dependent), improved clinical recovery, and lower hospitalization and mortality. In six RCTs of moderate or severe infection, there .. Details Source PDF

Meta

Hill et al., Research Square, doi:10.21203/rs.3.rs-148845/v1 (Preprint) (meta analysis) Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection Meta analysis of 18 ivermectin RCTs with 2,282 patients showing faster viral clearance (dose and duration dependent), improved clinical recovery, and lower hospitalization and mortality. In six RCTs of moderate or severe infection, there was a 75% reduction in mortality, RR 0.25 [0.12-0.52], p = 0.0002.A sponsor reportedly required the conclusion of this paper to be changed against the wishes of the authors (to suggest that more trials should be done as opposed to the existing evidence being sufficient) [1, 2, 3].

risk of death, 75.0% lower , RR 0.25, p .

Hill et al., 1/19/2021, preprint, 40 authors.

Submit Corrections or Comments Early 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 Details RCT 100 patients in Lebanon, showing significantly lower viral load at day 3, and lower hospitalization. All patients also took zinc and vitamin C. ChiCTR2000033627. Details Source PDF

Early treatment study

Samaha et al., Viruses, doi:10.3390/v13060989 (results 1/16) (Peer Reviewed) 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 RCT 100 patients in Lebanon, showing significantly lower viral load at day 3, and lower hospitalization. All patients also took zinc and vitamin C. ChiCTR2000033627.

risk of hospitalization, 85.7% lower , RR 0.14, p = 0.24 , treatment 0 of 50 (0.0%), control 3 of 50 (6.0%), continuity correction due to zero event.

risk of fever at day 3, 90.9% lower , RR 0.09, p = 0.004 , treatment 1 of 50 (2.0%), control 11 of 50 (22.0%).

Samaha et al., 1/16/2021, Randomized Controlled Trial, Lebanon, Middle East, peer-reviewed, 16 authors, dosage 12mg single dose, 45–64kg, 65–84kg, and >85kg patients received 9mg, 12mg, or 150µg/kg respectively.

Submit Corrections or Comments Early Bukhari et al., medRxiv, doi:10.1101/2021.02.02.21250840 (results 1/16) (Preprint) viral+, ↓82.4% , p Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease Details RCT of relatively low risk hospitalized patients with 50 ivermectin and 50 control patients showing significantly faster viral clearance with treatment. 9 patients in the treatment arm were lost to followup compared with 5 in the control .. Details Source PDF

Early treatment study

Bukhari et al., medRxiv, doi:10.1101/2021.02.02.21250840 (results 1/16) (Preprint) Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease RCT of relatively low risk hospitalized patients with 50 ivermectin and 50 control patients showing significantly faster viral clearance with treatment. 9 patients in the treatment arm were lost to followup compared with 5 in the control arm, which could be in part due to faster recovery with treatment. There were no safety concerns. No mortality was reported. The numbers in Table 3 are the number of patients that became negative on that day, i.e., non-cumulative. NCT04392713.

risk of no virological cure, 82.4% lower , RR 0.18, p , treatment 4 of 41 (9.8%), control 25 of 45 (55.6%), day 7.

risk of no virological cure, 38.7% lower , RR 0.61, p , treatment 24 of 41 (58.5%), control 43 of 45 (95.6%), day 3.

Bukhari et al., 1/16/2021, Randomized Controlled Trial, Pakistan, South Asia, preprint, 10 authors, dosage 12mg single dose.

Submit Corrections or Comments Review 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 Details Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19. This paper was censored by the journal after acceptance [.. Details Source PDF

Review

Kory et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.643369 (Review) (Peer Reviewed) Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19. This paper was censored by the journal after acceptance [1].

Kory et al., 1/13/2021, peer-reviewed, 10 authors.

Submit Corrections or Comments Late 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 Details Small RCT for severe COVID-19 comparing the addition of ivermectin to SOC (low dose HCQ+AZ+favipiravir), with 30 treatment and 30 control patients in Turkey, showing lower mortality and faster clinical recovery. Authors also investigate t.. Details Source PDF

Late treatment study

Okumuş et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06104-9 (preprint 1/12) (Peer Reviewed) Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Severe COVID-19 Patients Small RCT for severe COVID-19 comparing the addition of ivermectin to SOC (low dose HCQ+AZ+favipiravir), with 30 treatment and 30 control patients in Turkey, showing lower mortality and faster clinical recovery. Authors also investigate the presence of gene mutations that alter ivermectin metabolism, predicting that ivermectin can be used safely without serious side effects in patients without MDR-1/ABCB1 and/or CYP3A4 gene mutation, and recommending monitoring and appropriate treatment if necessary when sequencing is unavailable.

risk of death, 33.3% lower , RR 0.67, p = 0.55 , treatment 6 of 30 (20.0%), control 9 of 30 (30.0%).

risk of no improvement at day 10, 42.9% lower , RR 0.57, p = 0.18 , treatment 8 of 30 (26.7%), control 14 of 30 (46.7%).

risk of no improvement at day 5, 15.8% lower , RR 0.84, p = 0.60 , treatment 16 of 30 (53.3%), control 19 of 30 (63.3%).

risk of no virological cure, 80.0% lower , RR 0.20, p = 0.02 , treatment 2 of 16 (12.5%), control 5 of 8 (62.5%), day 10.

Okumuş et al., 1/12/2021, Double Blind Randomized Controlled Trial, Turkey, Europe, peer-reviewed, 15 authors, dosage 200μg/kg days 1-5, 36-50kg - 9mg, 51-65kg - 12mg, 66-79kg - 15mg, >80kg 200μg/kg.

Submit Corrections or Comments PrEPPEP Chahla et al., medRxiv, doi:10.1101/2021.03.26.21254398 (Preprint) m/s case, ↓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 Details Prophylaxis RCT for ivermectin and iota-carrageenan in Argentina, 117 healthcare workers treated with ivermectin and iota-carrageenan, and 117 controls, showing significantly lower cases with treatment. There were no moderate/severe cases.. Details Source PDF

Prophylaxis study

Chahla et al., medRxiv, doi:10.1101/2021.03.26.21254398 (Preprint) A randomized trial - intensive treatment based in ivermectin and iota-carrageenan as pre-exposure prophylaxis for COVID-19 in healthcare agents Prophylaxis RCT for ivermectin and iota-carrageenan in Argentina, 117 healthcare workers treated with ivermectin and iota-carrageenan, and 117 controls, showing significantly lower cases with treatment. There were no moderate/severe cases with treatment vs. 10 in the control group. There were 4 cases with treatment (all mild) vs. 25 for the control group. NCT04701710.

risk of moderate/severe case, 95.2% lower , RR 0.05, p = 0.002 , treatment 0 of 117 (0.0%), control 10 of 117 (8.5%), continuity correction due to zero event, moderate/severe COVID-19.

risk of COVID-19 case, 84.0% lower , RR 0.16, p , treatment 4 of 117 (3.4%), control 25 of 117 (21.4%), adjusted, OR converted to RR, all cases.

risk of COVID-19 case, 84.0% lower , RR 0.16, p , treatment 4 of 117 (3.4%), control 25 of 117 (21.4%), all cases.

Chahla et al., 1/11/2021, Randomized Controlled Trial, Argentina, South America, preprint, 1 author, dosage 12mg weekly, this trial uses multiple treatments in the treatment arm (combined with iota-carrageenan) - results of individual treatments may vary.

Submit Corrections or Comments N/A 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 Details Animal dosing study with an obese dog model concluding that ivermectin maintenance doses should be based on lean body weight and not the total body weight in obese subjects, while the loading dose should be based on the total body weight. Details Source PDF

N/A

Bousquet-Melou et al., Preprint, doi:10.22541/au.161047848.80388481/v1 (Preprint) Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients Animal dosing study with an obese dog model concluding that ivermectin maintenance doses should be based on lean body weight and not the total body weight in obese subjects, while the loading dose should be based on the total body weight.

Bousquet-Melou et al., 1/11/2021, preprint, 5 authors.

Submit Corrections or Comments Review 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 Details Review hypothesizing that micro- and nanotechnology-based formulations of ivermectin for the pulmonary delivery of ivermectin may be beneficial for use with COVID-19. Details Source PDF

Review

Formiga et al., J. Control Release, doi:10.1016/j.jconrel.2020.10.009 (Review) (Peer Reviewed) Ivermectin: an award-winning drug with expected antiviral activity against COVID-19 Review hypothesizing that micro- and nanotechnology-based formulations of ivermectin for the pulmonary delivery of ivermectin may be beneficial for use with COVID-19.

Formiga et al., 1/10/2021, peer-reviewed, 6 authors.

Submit Corrections or Comments Early Ravikirti et al., Journal of Pharmacy & Pharmaceutical Sciences, doi:10.18433/jpps32105 (Peer Reviewed) death, ↓88.7% , p=0.12 Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized placebo-controlled trial Details RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 .. Details Source PDF

Early treatment study

Ravikirti et al., Journal of Pharmacy & Pharmaceutical Sciences, doi:10.18433/jpps32105 (Peer Reviewed) Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized placebo-controlled trial RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 patients) versus 7% (4 of 57) in the control arm. The PCR result is subject to confounding by biased loss of followup, with 23 lost in the treatment group and 13 in the control group, and 8 more people in the treatment group discharged before day 6.

risk of death, 88.7% lower , RR 0.11, p = 0.12 , treatment 0 of 55 (0.0%), control 4 of 57 (7.0%), continuity correction due to zero event.

risk of mechanical ventilation, 79.3% lower , RR 0.21, p = 0.10 , treatment 1 of 55 (1.8%), control 5 of 57 (8.8%).

risk of ICU admission, 13.6% lower , RR 0.86, p = 0.80 , treatment 5 of 55 (9.1%), control 6 of 57 (10.5%).

risk of no virological cure, 11.6% higher , RR 1.12, p = 0.35 , treatment 42 of 55 (76.4%), control 39 of 57 (68.4%).

Ravikirti et al., 1/9/2021, Double Blind Randomized Controlled Trial, India, South Asia, peer-reviewed, 11 authors, dosage 12mg days 1, 2.

Submit Corrections or Comments Early Chamie , J. (News) news COVID-19 in Mexico Details Comparison of COVID-19 death rates in Mexico showing that the only state using ivermectin has a dramatically lower rate. Details Source PDF

Early treatment study

Chamie , J. (News) COVID-19 in Mexico Comparison of COVID-19 death rates in Mexico showing that the only state using ivermectin has a dramatically lower rate.

Chamie et al., 1/8/2021, preprint, 1 author.

Submit Corrections or Comments Early 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 Details Small RCT comparing ivermectin 6mg & 12mg q84hr with lopinavir/ritonavir, showing a statistically significant and dose dependent effect of ivermectin on reducing the time to PCR-. A twitter personality well known for negative attacks on .. Details Source PDF

Early treatment study

Babalola et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcab035 (preprint 1/6) (Peer Reviewed) Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos Small RCT comparing ivermectin 6mg & 12mg q84hr with lopinavir/ritonavir, showing a statistically significant and dose dependent effect of ivermectin on reducing the time to PCR-.A twitter personality well known for negative attacks on ivermectin suggests that there are clinical results which should be prioritized here. The paper does not report mortality, hospitalization, progression, recovery, etc. The paper does report change in SpO2 (Figure 3, ∆SpO2), where a similar improvement with a smaller p value is seen with ivermectin, however this result is unadjusted and there are large differences between groups. Specifically, baseline SpO2 is lower in the control group, giving the control group more room to improve, therefore the actual benefit of ivermectin is likely to be even larger than the benefit in ∆SpO2 shown. The twitter personality would like to cherry pick an unadjusted individual symptom like cough, for which baseline values differ by ~2x.

adjusted risk of viral+ at day 5, 63.9% lower , RR 0.36, p = 0.11 , treatment 40, control 20, adjusted.

risk of no virological cure, 58.0% lower , RR 0.42, p = 0.01 , treatment 20, control 20, 12mg - Cox proportional hazard model.

risk of no virological cure, 40.5% lower , RR 0.60, p = 0.12 , treatment 20, control 20, 6mg - Cox proportional hazard model.

time to viral-, 49.2% lower , relative time 0.51 , treatment 20, control 20, 12mg.

time to viral-, 34.4% lower , relative time 0.66 , treatment 20, control 20, 6mg.

Babalola et al., 1/6/2021, Double Blind Randomized Controlled Trial, Nigeria, Africa, peer-reviewed, baseline oxygen requirements 8.3%, 10 authors, dosage 12mg or 6mg q84h for two weeks, this trial compares with another treatment - results may be better when compared to placebo.

Submit Corrections or Comments PrEPPEP Hirsch et al., Microbiology & Infectious Diseases (Peer Reviewed) Ivermectin as Prophylaxis Against COVID-19 Retrospective Cases Evaluation Details Report on ivermectin prophylaxis for healthcare workers in a hospital in Argentina, showing 0 cases in the 162 participants. Dosage was 0.2mg/kg weekly for eight weeks, followed by 4 months rest. Details Source PDF

Prophylaxis study

Hirsch et al., Microbiology & Infectious Diseases (Peer Reviewed) Ivermectin as Prophylaxis Against COVID-19 Retrospective Cases Evaluation Report on ivermectin prophylaxis for healthcare workers in a hospital in Argentina, showing 0 cases in the 162 participants. Dosage was 0.2mg/kg weekly for eight weeks, followed by 4 months rest.

Hirsch et al., 1/6/2021, peer-reviewed, 2 authors.

Submit Corrections or Comments Early, Late, PrEP, PEP Lawrie et al., Preprint (Preprint) (meta analysis) death, ↓83.0% , p 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 Details Meta analysis confirming the effectiveness of ivermectin for COVID-19, showing ivermectin treatment mortality relative risk RR 0.17 [0.18-0.35] and prophylaxis cases RR 0.12 [0.08-0.18]. Details Source PDF

Early, Late, PrEP, PEP

Lawrie et al., Preprint (Preprint) (meta analysis) 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 Meta analysis confirming the effectiveness of ivermectin for COVID-19, showing ivermectin treatment mortality relative risk RR 0.17 [0.18-0.35] and prophylaxis cases RR 0.12 [0.08-0.18].

risk of death, 83.0% lower , RR 0.17, p , treatment 8 of 585 (1.4%), control 44 of 522 (8.4%).

Lawrie et al., 1/3/2021, preprint, 1 author.

Submit Corrections or Comments Late Wijaya et al., Cermin Dunia Kedokteran, 47:7 (Peer Reviewed) Ivermectin as a Potential Therapeutic Agent for COVID-19 – case studies Details Case report on 3 confirmed cases of COVID-19 with significant clinical and radiological improvement after a single dose of ivermectin. Details Source PDF

Late treatment study

Wijaya et al., Cermin Dunia Kedokteran, 47:7 (Peer Reviewed) Ivermectin as a Potential Therapeutic Agent for COVID-19 – case studies Case report on 3 confirmed cases of COVID-19 with significant clinical and radiological improvement after a single dose of ivermectin.

Wijaya et al., 12/31/2020, peer-reviewed, 2 authors.

Submit Corrections or Comments Animal 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 Details In vivo analysis of the safety of high dose ivermectin with a Corydoras fish animal model. Details Source PDF

Animal study

Madrid et al., Heliyon, doi:10.1016/j.heliyon.2020.e05820 (Peer Reviewed) Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation In vivo analysis of the safety of high dose ivermectin with a Corydoras fish animal model.

Madrid et al., 12/31/2020, peer-reviewed, 8 authors.

Submit Corrections or Comments Review 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) Details Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may .. Details Source PDF

Review

McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may include >=2 of HCQ, ivermectin, favipiravir; AZM/DOXY; corticosteroids; colchicine; bamlanivimab; aspirin; LMWH; and supplemental oxygen.

McCullough et al., 12/30/2020, peer-reviewed, 58 authors.

Submit Corrections or Comments Early 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 Details Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region. At least two of z.. Details Source PDF

Early treatment study

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 Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region.At least two of zinc, HCQ, and ivermectin were used, along with one antibiotic, and budesonide and/or dexamethasone.

Procter et al., 12/30/2020, peer-reviewed, 6 authors.

Submit Corrections or Comments Meta Hill , A., Preprint (Preprint) (meta analysis) meta-analysis Meta-analysis of clinical trials of ivermectin to treat COVID-19 infection Details WHO-funded meta analysis showing ivermectin treatment mortality relative risk RR 0.17 [0.08-0.35] for RCTs and RR 0.28 [0.13-0.62] for RCTs and observational studies, and confirming a dose-response effect. Details Source PDF

Meta

Hill , A., Preprint (Preprint) (meta analysis) Meta-analysis of clinical trials of ivermectin to treat COVID-19 infection WHO-funded meta analysis showing ivermectin treatment mortality relative risk RR 0.17 [0.08-0.35] for RCTs and RR 0.28 [0.13-0.62] for RCTs and observational studies, and confirming a dose-response effect.

Hill et al., 12/27/2020, preprint, 1 author.

Submit Corrections or Comments In Vitro 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 Details In Vitro study showing enhanced antiviral activity of ivermectin and remdesivir in combination. Details Source PDF

In Vitro

Jeffreys et al., bioRxiv, doi:10.1101/2020.12.23.424232 (Preprint) (In Vitro) Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2 In Vitro study showing enhanced antiviral activity of ivermectin and remdesivir in combination.

Jeffreys et al., 12/24/2020, preprint, 15 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments PrEPPEP Vallejos et al., Preliminary Results (Preprint) cases, ↓73.4% , p Ivermectina en agentes de salud e IVERCOR COVID19 Details Report on ivermectin prophylaxis in a hospital in Argentina showing lower cases for healthcare workers taking ivermectin. Preliminary results from: [1]. Details Source PDF

Prophylaxis study

Vallejos et al., Preliminary Results (Preprint) Ivermectina en agentes de salud e IVERCOR COVID19 Report on ivermectin prophylaxis in a hospital in Argentina showing lower cases for healthcare workers taking ivermectin. Preliminary results from: [1].

risk of COVID-19 case, 73.4% lower , RR 0.27, p , treatment 13 of 389 (3.3%), control 61 of 486 (12.6%).

Vallejos et al., 12/20/2020, retrospective, Argentina, South America, preprint, 1 author, dosage 12mg weekly.

Submit Corrections or Comments Early, Late, PrEP, PEP Kory et al., FLCCC Alliance (Preprint) (meta analysis) death, ↓69.0% , p Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 Details Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19. Details Source PDF

Early, Late, PrEP, PEP

Kory et al., FLCCC Alliance (Preprint) (meta analysis) Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 Meta analysis of ivermectin clinical studies and natural experiments where ivermectin has been widely used, showing efficacy of ivermectin in prophylaxis and treatment of COVID-19.

risk of death, 69.0% lower , RR 0.31, p , treatment 35 of 1551 (2.3%), control 191 of 1957 (9.8%), OR converted to RR.

Kory et al., 12/18/2020, preprint, 10 authors.

Submit Corrections or Comments PrEPPEP Alam et al., European Journal ofMedical and Health Sciences, doi:10.24018/ejmed.2020.2.6.599 (Peer Reviewed) cases, ↓90.6% , p Ivermectin as Pre-exposure Prophylaxis for COVID-19 among Healthcare Providers in a Selected Tertiary Hospital in Dhaka – An Observational Study Details 91% reduction in COVID-19 cases with ivermectin prophylaxis. 118 healthcare workers in Bangladesh, 58 receiving ivermectin 12mg monthly, showing RR 0.094, p Details Source PDF

Prophylaxis study

Alam et al., European Journal ofMedical and Health Sciences, doi:10.24018/ejmed.2020.2.6.599 (Peer Reviewed) Ivermectin as Pre-exposure Prophylaxis for COVID-19 among Healthcare Providers in a Selected Tertiary Hospital in Dhaka – An Observational Study 91% reduction in COVID-19 cases with ivermectin prophylaxis. 118 healthcare workers in Bangladesh, 58 receiving ivermectin 12mg monthly, showing RR 0.094, p

risk of COVID-19 case, 90.6% lower , RR 0.09, p , treatment 4 of 58 (6.9%), control 44 of 60 (73.3%).

Alam et al., 12/15/2020, prospective, Bangladesh, South Asia, peer-reviewed, 13 authors, dosage 12mg monthly.

Submit Corrections or Comments Early 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 Details Small 95 patient study in Pakistan adding ivermectin to standard of care (HCQ+AZ) for outpatients with mild/moderate suspected COVID-19, showing faster resolution of fever with ivermectin. The low dose HCQ used in this study may not reac.. Details Source PDF

Early treatment study

Afsar et al., SSRN (Preprint) Ivermectin Use Associated with Reduced Duration of COVID-19 Febrile Illness in a Community Setting Small 95 patient study in Pakistan adding ivermectin to standard of care (HCQ+AZ) for outpatients with mild/moderate suspected COVID-19, showing faster resolution of fever with ivermectin.The low dose HCQ used in this study may not reach therapeutic levels fast enough to make a significant impact.

risk of fever at day 14, 92.2% lower , RR 0.08, p = 0.04 , treatment 0 of 37 (0.0%), control 7 of 53 (13.2%), continuity correction due to zero event.

Afsar et al., 12/15/2020, retrospective, Pakistan, South Asia, preprint, 6 authors, dosage 12mg days 1-6.

Submit Corrections or Comments Early Hussain et al., International Journal of Molecular and Immuno Oncology, doi:10.25259/IJMIO_30_2020 (Preprint) Outcome of ivermectin and doxycycline in cancer patients with COVID-19: A positive experience in Bangladesh Details Small case study of ivermectin + doxycycline with 8 cancer patients, with all patients becoming PCR- by day 6 when tested again. Details Source PDF

Early treatment study

Hussain et al., International Journal of Molecular and Immuno Oncology, doi:10.25259/IJMIO_30_2020 (Preprint) Outcome of ivermectin and doxycycline in cancer patients with COVID-19: A positive experience in Bangladesh Small case study of ivermectin + doxycycline with 8 cancer patients, with all patients becoming PCR- by day 6 when tested again.

Hussain et al., 12/11/2020, preprint, 3 authors.

Submit Corrections or Comments Early Chaccour et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720 (preprint 12/7) (Peer Reviewed) symp. prob., ↓52.9% , p 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 Details Tiny RCT for early treatment of mild COVID-19 in low risk patients, with 12 400mcg/kg single dose ivermectin patients and 12 control patients, showing significantly faster viral load reduction and symptom improvement with ivermectin. Ave.. Details Source PDF

Early treatment study

Chaccour et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720 (preprint 12/7) (Peer Reviewed) 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 Tiny RCT for early treatment of mild COVID-19 in low risk patients, with 12 400mcg/kg single dose ivermectin patients and 12 control patients, showing significantly faster viral load reduction and symptom improvement with ivermectin.Average median viral load for gene E and gene N mid-viral recovery at day 7:Ivermectin: 1637
control: 30175Probability of symptoms at day 28, adjusted for the time since onset and day of followup:Ivermectin: = 0.26 [0.10-0.42]
control: 0.55 [0.33-0.77](details are in the supplementary appendix)

symptom probability, 52.9% lower , RR 0.47, p , treatment 12, control 12, relative probability of symptoms at day 28, mixed effects logistic regression, data in supplementary appendix.

viral load, 94.6% lower , relative load 0.05 , treatment 12, control 12, day 7 mid-recovery, data in supplementary appendix.

Chaccour et al., 12/7/2020, Double Blind Randomized Controlled Trial, Spain, Europe, peer-reviewed, 23 authors, dosage 400μg/kg single dose.

Submit Corrections or Comments Meta Kalfas et al., medRxiv, doi:10.1101/2020.11.30.20236570 (Preprint) (meta analysis) meta-analysis The therapeutic potential of ivermectin for COVID-19: a systematic review of mechanisms and evidence Details Review of ivermectin mechanisms and 8 trials, showing positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression, and decreased duration of hospital admission in patients across all stages of c.. Details Source PDF

Meta

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 Review of ivermectin mechanisms and 8 trials, showing positive mortality benefit, reduced time to clinical recovery, reduced incidence of disease progression, and decreased duration of hospital admission in patients across all stages of clinical severity.

Kalfas et al., 12/4/2020, preprint, 4 authors.

Submit Corrections or Comments In Vitro 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 Details In Vitro analysis of ivermectin with orally administrable nanoparticles showing efficacy for decreasing expression of the viral spike protein and ACE2. Inhibition of nuclear transport activities mediated through proteins such as importin .. Details Source PDF

In Vitro

Surnar et al., ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179 (Peer Reviewed) (In Vitro) Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19 In Vitro analysis of ivermectin with orally administrable nanoparticles showing efficacy for decreasing expression of the viral spike protein and ACE2. Inhibition of nuclear transport activities mediated through proteins such as importin α/β1 heterodimer are also considered as a possible mechanism of action. The technology may work for other coronaviruses as well.

Surnar et al., 12/4/2020, peer-reviewed, 4 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Early 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 Details Small 72 patient RCT of ivermectin and ivermectin + doxycycline showing faster recovery with ivermectin. Ivermectin group: 12mg daily for 5 days Ivermectin + doxycycline: 12mg ivermectin single dose, 200mg doxycycline + 100mg bid 4 days Details Source PDF

Early treatment study

Ahmed et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.191 (Peer Reviewed) A five day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness Small 72 patient RCT of ivermectin and ivermectin + doxycycline showing faster recovery with ivermectin.Ivermectin group: 12mg daily for 5 days
Ivermectin + doxycycline: 12mg ivermectin single dose, 200mg doxycycline + 100mg bid 4 days

risk of unresolved symptoms, 85.0% lower , RR 0.15, p = 0.09 , treatment 0 of 17 (0.0%), control 3 of 19 (15.8%), continuity correction due to zero event, day 7 fever ivermectin.

risk of unresolved symptoms, 62.7% lower , RR 0.37, p = 0.35 , treatment 1 of 17 (5.9%), control 3 of 19 (15.8%), day 7 fever ivermectin + doxycycline.

risk of no virological cure, 42.5% lower , RR 0.58, p = 0.01 , treatment 11 of 22 (50.0%), control 20 of 23 (87.0%), day 7 ivermectin.

risk of no virological cure, 20.0% lower , RR 0.80, p = 0.28 , treatment 16 of 23 (69.6%), control 20 of 23 (87.0%), day 7 ivermectin + doxycycline.

risk of no virological cure, 62.7% lower , RR 0.37, p = 0.02 , treatment 5 of 22 (22.7%), control 14 of 23 (60.9%), day 14 ivermectin.

risk of no virological cure, 35.7% lower , RR 0.64, p = 0.24 , treatment 9 of 23 (39.1%), control 14 of 23 (60.9%), day 14 ivermectin + doxycycline.

time to viral-, 23.6% lower , relative time 0.76, p = 0.02 , treatment 22, control 23, ivermectin.

time to viral-, 9.4% lower , relative time 0.91, p = 0.27 , treatment 23, control 23, ivermectin + doxycycline.

hospitalization time, 1.0% lower , relative time 0.99 , ivermectin.

hospitalization time, 4.1% higher , relative time 1.04 , ivermectin + doxycycline.

Ahmed et al., 12/2/2020, Double Blind Randomized Controlled Trial, Bangladesh, South Asia, peer-reviewed, mean age 42.0, 15 authors, dosage 12mg days 1-5, ivermectin + doxycycline group took only a single dose of ivermectin.

Submit Corrections or Comments Early Chamie , J. (News) news The effect of using ivermectin to control COVID-19 in Chiapas Details After starting to distribute ivermectin in drug kits in July, the Mexican state of Chiapas has seen a dramatic divergence from other states with much lower mortality [1, 2]. Details Source PDF

Early treatment study

Chamie , J. (News) The effect of using ivermectin to control COVID-19 in Chiapas After starting to distribute ivermectin in drug kits in July, the Mexican state of Chiapas has seen a dramatic divergence from other states with much lower mortality [1, 2].

Chamie et al., 12/2/2020, preprint, 1 author.

Submit Corrections or Comments Early Alonso et al., (Preprint) death, ↓91.8% , p=0.009 COVID-19: Uso de ivermectina Details Observational study in Argentina showing significantly lower mortality in the 60 days after adopting ivermectin compared to the 60 days before, relative risk RR 0.082, p=0.003. Details Source PDF

Early treatment study

Alonso et al., (Preprint) COVID-19: Uso de ivermectina Observational study in Argentina showing significantly lower mortality in the 60 days after adopting ivermectin compared to the 60 days before, relative risk RR 0.082, p=0.003.

risk of death, 91.8% lower , RR 0.08, p = 0.009 , treatment 1 of 311 (0.3%), control 5 of 128 (3.9%).

Alonso et al., 12/1/2020, retrospective, Argentina, South America, preprint, 1 author, dosage not specified.

Submit Corrections or Comments PrEPPEP 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 Details 69 residents of a French care home, median age 90, were treated with ivermectin for a scabies outbreak. 3,062 residents in 45 nearby comparable homes were used as controls. 7 of 69 treated patients had probable or certain COVID-19, with .. Details Source PDF

Prophylaxis study

Bernigaud et al., Annals of Dermatology and Venereology, doi:10.1016/j.annder.2020.09.231 (Peer Reviewed) Ivermectin benefit: from scabies to COVID-19, an example of serendipity 69 residents of a French care home, median age 90, were treated with ivermectin for a scabies outbreak. 3,062 residents in 45 nearby comparable homes were used as controls.7 of 69 treated patients had probable or certain COVID-19, with no serious cases and no deaths. In comparable care homes in the same district, matched by age and socio-economic level, there was 22.6% COVID-19 and 5% death.

risk of death, 99.4% lower , RR 0.006, p = 0.08 , treatment 0 of 69 (0.0%), control 150 of 3062 (4.9%), continuity correction due to zero event.

risk of COVID-19 case, 55.1% lower , RR 0.45, p = 0.01 , treatment 7 of 69 (10.1%), control 692 of 3062 (22.6%).

Bernigaud et al., 11/28/2020, retrospective, France, Europe, peer-reviewed, 12 authors, dosage 200μg/kg days 1, 8, 15, 400μg/kg days 1, 8, 15, two different dosages.

Submit Corrections or Comments PrEPPEP Hellwig et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106248 (Peer Reviewed) cases, ↓78.0% , p A COVID-19 Prophylaxis? Lower incidence associated with prophylactic administration of Ivermectin Details Analysis of COVID-19 cases vs. widespread prophylactic use of ivermectin for parasitic infections showing significantly lower incidence of COVID-19 cases. Details Source PDF

Prophylaxis study

Hellwig et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106248 (Peer Reviewed) A COVID-19 Prophylaxis? Lower incidence associated with prophylactic administration of Ivermectin Analysis of COVID-19 cases vs. widespread prophylactic use of ivermectin for parasitic infections showing significantly lower incidence of COVID-19 cases.

risk of COVID-19 case, 78.0% lower , RR 0.22, p , African countries, PCTI vs. no PCT, relative cases per capita.

risk of COVID-19 case, 80.0% lower , RR 0.20, p , worldwide, PCTI vs. no PCT, relative cases per capita.

Hellwig et al., 11/28/2020, retrospective, ecological study, multiple countries, multiple regions, peer-reviewed, 2 authors, dosage 200μg/kg, dose varied, typically 150-200μg/kg.

Submit Corrections or Comments Late Niaee et al., Asian Pacific Journal of Tropical Medicine, doi:10.4103/1995-7645.318304 (preprint 11/24/20) (Peer Reviewed) death, ↓81.8% , p=0.001 Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial Details 82% lower mortality with ivermectin. RCT with 180 hospitalized patients showing reduced mortality and hospital stay with ivermectin, with a wide margin of safety. All patients received SOC including low dose HCQ. Details Source PDF

Late treatment study

Niaee et al., Asian Pacific Journal of Tropical Medicine, doi:10.4103/1995-7645.318304 (preprint 11/24/20) (Peer Reviewed) Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial 82% lower mortality with ivermectin. RCT with 180 hospitalized patients showing reduced mortality and hospital stay with ivermectin, with a wide margin of safety. All patients received SOC including low dose HCQ.

risk of death, 81.8% lower , RR 0.18, p = 0.001 , treatment 4 of 120 (3.3%), control 11 of 60 (18.3%), All IVM vs. all control.

risk of death, 94.3% lower , RR 0.06, p = 0.01 , treatment 0 of 30 (0.0%), control 11 of 60 (18.3%), continuity correction due to zero event, IVM single dose 200mcg/kg vs. all control.

risk of death, 45.5% lower , RR 0.55, p = 0.37 , treatment 3 of 30 (10.0%), control 11 of 60 (18.3%), IVM three dose 200mcg/kg vs. all control.

risk of death, 94.3% lower , RR 0.06, p = 0.01 , treatment 0 of 30 (0.0%), control 11 of 60 (18.3%), continuity correction due to zero event, IVM single dose 400mcg/kg vs. all control.

risk of death, 81.8% lower , RR 0.18, p = 0.06 , treatment 1 of 30 (3.3%), control 11 of 60 (18.3%), IVM three dose 400/200/200mcg/kg vs. all control.

Niaee et al., 11/24/2020, Double Blind Randomized Controlled Trial, Iran, Middle East, peer-reviewed, mean age 56.0, 14 authors, dosage 400μg/kg single dose, dose varies in different groups.

Submit Corrections or Comments Animal de Melo et al., EMBO Mol. Med., doi:10.15252/emmm.202114122 (preprint 11/22/20) (Peer Reviewed) animal study Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin Details Animal study showing that standard doses of ivermectin prevented clinical deterioration, reduced olfactory deficit, and limited the inflammation of the upper and lower respiratory tracts in SARS-CoV-2-infected hamsters. Details Source PDF

Animal study

de Melo et al., EMBO Mol. Med., doi:10.15252/emmm.202114122 (preprint 11/22/20) (Peer Reviewed) Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin Animal study showing that standard doses of ivermectin prevented clinical deterioration, reduced olfactory deficit, and limited the inflammation of the upper and lower respiratory tracts in SARS-CoV-2-infected hamsters.

de Melo et al., 11/22/2020, peer-reviewed, 11 authors.

Submit Corrections or Comments Late 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 Details Retrospective 976 hospitalized patients with 34 treated with ivermectin showing ivermectin mortality relative risk RR 0.13, p = 0.04. Details Source PDF

Late treatment study

Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223 (Preprint) Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience Retrospective 976 hospitalized patients with 34 treated with ivermectin showing ivermectin mortality relative risk RR 0.13, p = 0.04.

risk of death, 99.1% lower , RR 0.009, p = 0.04 , treatment 0 of 34 (0.0%), control 103 of 942 (10.9%), continuity correction due to zero event.

Budhiraja et al., 11/18/2020, retrospective, India, South Asia, preprint, 12 authors, dosage not specified.

Submit Corrections or Comments PrEPPEP Carvallo et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1007 (Peer Reviewed) cases, ↓99.9% , p Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel Details Prophylaxis study using ivermectin and iota-carrageenan showing 0 of 788 cases from treated healthcare workers, compared to 237 of 407 control. The authors later reported that carrageenan is not necessary in this protocol [1]. Details Source PDF

Prophylaxis study

Carvallo et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1007 (Peer Reviewed) Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel Prophylaxis study using ivermectin and iota-carrageenan showing 0 of 788 cases from treated healthcare workers, compared to 237 of 407 control.The authors later reported that carrageenan is not necessary in this protocol [1].

risk of COVID-19 case, 99.9% lower , RR 0.001, p , treatment 0 of 788 (0.0%), control 237 of 407 (58.2%), continuity correction due to zero event.

Carvallo et al., 11/17/2020, prospective, Argentina, South America, peer-reviewed, 4 authors, dosage 12mg weekly, this trial uses multiple treatments in the treatment arm (combined with iota-carrageenan) - results of individual treatments may vary.

Submit Corrections or Comments Late 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 Details 100 patient prospective trial of ivermectin + doxycycline showing reduced time to symptom resolution and shorter hospital stay with treatment. Details Source PDF

Late treatment study

Spoorthi et al., IAIM, 2020, 7:10, 177-182 (Peer Reviewed) Utility of Ivermectin and Doxycycline combination for the treatment of SARSCoV-2 100 patient prospective trial of ivermectin + doxycycline showing reduced time to symptom resolution and shorter hospital stay with treatment.

recovery time, 21.1% lower , relative time 0.79, p = 0.03 , treatment 50, control 50.

hospitalization time, 15.5% lower , relative time 0.84, p = 0.01 , treatment 50, control 50.

Spoorthi et al., 11/14/2020, prospective, India, South Asia, peer-reviewed, 2 authors, dosage not specified, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.

Submit Corrections or Comments Late Elgazzar et al., Research Square, doi:10.21203/rs.3.rs-100956/v2 (Preprint) Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic Details This study was withdrawn. Details Source PDF

Late treatment study

Elgazzar et al., Research Square, doi:10.21203/rs.3.rs-100956/v2 (Preprint) Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic This study was withdrawn.

Elgazzar et al., 11/13/2020, preprint, 6 authors.

Submit Corrections or Comments Late 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 Details Tiny 26 patients retrospective study of ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses. All patients received HCQ whi.. Details Source PDF

Late treatment study

Camprubí et al., PLoS ONE, 15:11, doi:10.1371/journal.pone.0242184 (Peer Reviewed) Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients Tiny 26 patients retrospective study of ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses.All patients received HCQ which may reduce the potential benefit for adding ivermectin.

risk of mechanical ventilation, 40.0% lower , RR 0.60, p = 0.67 , treatment 3 of 13 (23.1%), control 5 of 13 (38.5%).

risk of ICU admission, 33.3% lower , RR 0.67, p = 1.00 , treatment 2 of 13 (15.4%), control 3 of 13 (23.1%), ICU at day 8.

risk of no improvement at day 8, 33.3% higher , RR 1.33, p = 1.00 , treatment 4 of 13 (30.8%), control 3 of 13 (23.1%).

Camprubí et al., 11/11/2020, retrospective, Spain, Europe, peer-reviewed, 9 authors, dosage 200μg/kg single dose.

Submit Corrections or Comments Review Turkia , M., ResearchGate (Review) (Preprint) review FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review Details Review suggesting that ivermectin should be used based on existing data suggesting significant benefits, and that waiting for additional data may result in significant harm. Details Source PDF

Review

Turkia , M., ResearchGate (Review) (Preprint) FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review Review suggesting that ivermectin should be used based on existing data suggesting significant benefits, and that waiting for additional data may result in significant harm.

Turkia et al., 11/10/2020, preprint, 1 author.

Submit Corrections or Comments Early Cadegiani et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100915 (preprint 11/4/2020) (Peer Reviewed) death, ↓78.3% , p=0.50 Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients Details Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, ev.. Details Source PDF

Early treatment study

Cadegiani et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100915 (preprint 11/4/2020) (Peer Reviewed) Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.

risk of death, 78.3% lower , RR 0.22, p = 0.50 , treatment 0 of 110 (0.0%), control 2 of 137 (1.5%), continuity correction due to zero event, control group 1.

risk of mechanical ventilation, 94.2% lower , RR 0.06, p = 0.005 , treatment 0 of 110 (0.0%), control 9 of 137 (6.6%), continuity correction due to zero event, control group 1.

risk of hospitalization, 98.0% lower , RR 0.02, p , treatment 0 of 110 (0.0%), control 27 of 137 (19.7%), continuity correction due to zero event, control group 1.

Cadegiani et al., 11/4/2020, prospective, Brazil, South America, peer-reviewed, 4 authors, dosage 200μg/kg days 1-3, this trial uses multiple treatments in the treatment arm (combined with AZ, nitazoxanide (82), HCQ (22), spironolactone (66), dutasteride (4)) - results of individual treatments may vary.

Submit Corrections or Comments Early, 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 Details Retrospective 3,099 outpatients treated with ivermectin in an ER. Of 2,706 treated on an outpatient basis, 18 were subsequently hospitalized, 2 in the ICU, and there was one death (0.04%). The average treatment delay for patients treated.. Details Source PDF

Early, 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 Retrospective 3,099 outpatients treated with ivermectin in an ER. Of 2,706 treated on an outpatient basis, 18 were subsequently hospitalized, 2 in the ICU, and there was one death (0.04%).The average treatment delay for patients treated on an outpatient basis was 3.6 days, compared to 6.9 days for hospitalized patients, and 7.8 days for ICU patients.For the 300 late treatment hospitalized patients there was 3 deaths. For the 111 very late treatment ICU patients there was 34 deaths.

Morgenstern et al., 11/3/2020, peer-reviewed, 14 authors.

Submit Corrections or Comments PrEPPEP Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) cases, ↓53.8% , p Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study Details Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, .. Details Source PDF

Prophylaxis study

Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin.HCQ OR 0.56, p = 0.29
Ivermectin OR 0.27, p Vitamin C OR 0.82, p = 0.58

risk of COVID-19 case, 53.8% lower , RR 0.46, p , treatment 41 of 117 (35.0%), control 145 of 255 (56.9%), adjusted, OR converted to RR, model 2 2+ doses conditional logistic regression.

risk of COVID-19 case, 44.5% lower , RR 0.56, p , treatment 41 of 117 (35.0%), control 145 of 255 (56.9%), OR converted to RR, matched pair analysis.

Behera et al., 11/3/2020, retrospective, India, South Asia, peer-reviewed, 13 authors, dosage 300μg/kg days 1, 4.

Submit Corrections or Comments Animal 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 Details Mouse study showing ivermectin reducing MHV viral load and disease. MHV is a type 2 family RNA coronavirus similar to SARS-CoV2. Details Source PDF

Animal study

Arévalo et al., Scientific Reports, doi:10.1038/s41598-021-86679-0 (preprint 11/2/20) (Peer Reviewed) Ivermectin reduces in vivo coronavirus infection in a mouse experimental model Mouse study showing ivermectin reducing MHV viral load and disease. MHV is a type 2 family RNA coronavirus similar to SARS-CoV2.

Arévalo et al., 11/2/2020, peer-reviewed, 12 authors.

Submit Corrections or Comments PrEPPEP Chang et al., ResearchGate (Preprint) COVID-19: Effectiveness of pre-exposure prophylaxis with ivermectin in exposed persons Details Pre-exposure prophylaxis study with 129 people split into high/low exposure groups, with each group split into different dosing regimens, showing higher effectivess with more frequent doses. High-exposure group: every 7 days dosing: 0 o.. Details Source PDF

Prophylaxis study

Chang et al., ResearchGate (Preprint) COVID-19: Effectiveness of pre-exposure prophylaxis with ivermectin in exposed persons Pre-exposure prophylaxis study with 129 people split into high/low exposure groups, with each group split into different dosing regimens, showing higher effectivess with more frequent doses.High-exposure group:every 7 days dosing: 0 of 20 cases, 100% effective
every 14 days dosing: 1 of 47 cases, 98% effective
every 30 days dosing: 2 of 20 cases, 90% effectiveLow-exposure group:every 14 days dosing: 0 of 21 cases, 100% effective
every 30 days dosing: 1 of 20 cases, 95% effective

Chang et al., 10/31/2020, preprint, 2 authors.

Submit Corrections or Comments Early 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 Details Retrospective 717 patients in Brazil showing OR 1.17 [0.72-1.90] for ivermectin. This paper focuses on HCQ, event counts for ivermectin are not provided. With significant correlation between the variables used, including overlap in the pr.. Details Source PDF

Early treatment study

Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed) Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis Retrospective 717 patients in Brazil showing OR 1.17 [0.72-1.90] for ivermectin. This paper focuses on HCQ, event counts for ivermectin are not provided. With significant correlation between the variables used, including overlap in the prescription of multiple treatments that show efficacy alone, and limited data for the model size, the model used here may be inaccurate due to multicollinearity [1].

risk of hospitalization, 13.9% higher , RR 1.14, p = 0.45 , treatment 340, control 377, adjusted, OR converted to RR, control prevalence approximated with overall prevalence.

Szente Fonseca et al., 10/31/2020, retrospective, Brazil, South America, peer-reviewed, mean age 50.6, 10 authors, dosage 12mg days 1-2.

Submit Corrections or Comments Late Hashim et al., Iraqi Journal of Medical Science, 19:1 (Peer Reviewed) death, ↓91.7% , p=0.03 Controlled randomized clinical trial on using Ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq Details RCT 70 ivermectin+doxycycline patients and 70 control patients showing reduced time to recovery and reduced mortality with treatment. Earlier treatment was more successful. For ethical reasons, critical patients were all in the treatment .. Details Source PDF

Late treatment study

Hashim et al., Iraqi Journal of Medical Science, 19:1 (Peer Reviewed) Controlled randomized clinical trial on using Ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq RCT 70 ivermectin+doxycycline patients and 70 control patients showing reduced time to recovery and reduced mortality with treatment. Earlier treatment was more successful. For ethical reasons, critical patients were all in the treatment group.

risk of death, 91.7% lower , RR 0.08, p = 0.03 , treatment 0 of 59 (0.0%), control 6 of 70 (8.6%), continuity correction due to zero event, excluding non-randomized critical patients.

risk of death, 67.1% lower , RR 0.33, p = 0.16 , treatment 2 of 70 (2.9%), control 6 of 70 (8.6%), OR converted to RR, including critical patients which were always allocated to treatment.

risk of disease progression, 83.1% lower , RR 0.17, p = 0.07 , treatment 1 of 59 (1.7%), control 7 of 70 (10.0%), excluding non-randomized critical patients.

risk of disease progression, 57.4% lower , RR 0.43, p = 0.20 , treatment 3 of 70 (4.3%), control 7 of 70 (10.0%), OR converted to RR, including critical patients which were always allocated to treatment.

recovery time, 40.7% lower , relative time 0.59, p , treatment 70, control 70.

Hashim et al., 10/26/2020, Single Blind Randomized Controlled Trial, Iraq, Middle East, peer-reviewed, 7 authors, dosage 200μg/kg days 1-2, some patients received a third dose on day 8, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.

Submit Corrections or Comments PrEPPEP Guerrero et al., Colombia Médica, doi:10.25100/cm.v51i4.4613 (Peer Reviewed) COVID-19: The Ivermectin African Enigma Details Study of African Programme for Onchocerciasis Control (APOC) countries, which used ivermectin, with non-APOC countries in Africa, showing 28% lower mortality for APOC countries, relative risk RR = 0.72 [0.67-0.78]. See also [1] and the au.. Details Source PDF

Prophylaxis study

Guerrero et al., Colombia Médica, doi:10.25100/cm.v51i4.4613 (Peer Reviewed) COVID-19: The Ivermectin African Enigma Study of African Programme for Onchocerciasis Control (APOC) countries, which used ivermectin, with non-APOC countries in Africa, showing 28% lower mortality for APOC countries, relative risk RR = 0.72 [0.67-0.78]. See also [1] and the author's response [2].

Guerrero et al., 10/22/2020, peer-reviewed, 5 authors.

Submit Corrections or Comments PrEPPEP Carvallo et al., NCT04425850 (Preprint) cases, ↓96.3% , p Usefulness of Topic Ivermectin and Carrageenan to Prevent Contagion of Covid 19 (IVERCAR) Details Prophylaxis study using ivermectin and carrageenan showing 0 of 131 cases from treated healthcare workers, compared to 11 of 98 control. The effect is likely to be primarily due to ivermectin - the author has later reported that carragee.. Details Source PDF

Prophylaxis study

Carvallo et al., NCT04425850 (Preprint) Usefulness of Topic Ivermectin and Carrageenan to Prevent Contagion of Covid 19 (IVERCAR) Prophylaxis study using ivermectin and carrageenan showing 0 of 131 cases from treated healthcare workers, compared to 11 of 98 control.The effect is likely to be primarily due to ivermectin - the author has later reported that carrageenan is not necessary [1].

risk of COVID-19 case, 96.3% lower , RR 0.04, p , treatment 0 of 131 (0.0%), control 11 of 98 (11.2%), continuity correction due to zero event.

Carvallo et al., 10/19/2020, prospective, Argentina, South America, preprint, 1 author, dosage 1mg days 1-14, this trial uses multiple treatments in the treatment arm (combined with iota-carrageenan) - results of individual treatments may vary.

Submit Corrections or Comments Animal 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 Details Study showing that nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats. Authors note that additional experiments are required to assess the safety of this formulation in larger animals. Details Source PDF

Animal study

Chaccour et al., Scientific Reports, doi:10.1038/s41598-020-74084-y (Peer Reviewed) Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats Study showing that nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats. Authors note that additional experiments are required to assess the safety of this formulation in larger animals.

Chaccour et al., 10/13/2020, peer-reviewed, 8 authors.

Submit Corrections or Comments Late 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) Details Retrospective 280 hospitalized patients showing lower mortality with ivermectin (13.3% vs 24.5%), propensity matched odds ratio OR 0.47 [0.22-0.99], p=0.045. Details Source PDF

Late treatment study

Rajter et al., Chest, doi:10.1016/j.chest.2020.10.009 (Peer Reviewed) Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID-19 (ICON study) Retrospective 280 hospitalized patients showing lower mortality with ivermectin (13.3% vs 24.5%), propensity matched odds ratio OR 0.47 [0.22-0.99], p=0.045.

risk of death, 46.0% lower , RR 0.54, p = 0.04 , treatment 13 of 98 (13.3%), control 24 of 98 (24.5%), adjusted, OR converted to RR, PSM.

risk of death, 66.9% lower , RR 0.33, p = 0.03 , treatment 26 of 173 (15.0%), control 27 of 107 (25.2%), adjusted, OR converted to RR, multivariate.

risk of mechanical ventilation, 63.6% lower , RR 0.36, p = 0.10 , treatment 4 of 98 (4.1%), control 11 of 98 (11.2%), matched cohort excluding intubated at baseline.

Rajter et al., 10/13/2020, retrospective, propensity score matching, USA, North America, peer-reviewed, 6 authors, dosage 200μg/kg single dose.

Submit Corrections or Comments Early 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 Details RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are n.. Details Source PDF

Early treatment study

Mahmud et al., Journal of International Medical Research, doi:10.5061/dryad.qjq2bvqf6 (preprint 10/9/20) (Peer Reviewed) Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are not included in the analysis of other outcomes). NCT04523831.

risk of death, 85.7% lower , RR 0.14, p = 0.25 , treatment 0 of 183 (0.0%), control 3 of 183 (1.6%), continuity correction due to zero event.

risk of disease progression, 57.0% lower , RR 0.43, p , treatment 16 of 183 (8.7%), control 32 of 180 (17.8%), adjusted, Cox regression.

risk of no recovery, 94.0% lower , RR 0.06, p , treatment 72 of 183 (39.3%), control 100 of 180 (55.6%), adjusted, day 7, Cox regression.

risk of no recovery, 38.5% lower , RR 0.61, p = 0.005 , treatment 40 of 183 (21.9%), control 64 of 180 (35.6%), day 11.

risk of no recovery, 96.0% lower , RR 0.04, p , treatment 42 of 183 (23.0%), control 67 of 180 (37.2%), adjusted, day 12, Cox regression.

time to recovery, 27.0% lower , RR 0.73, p = 0.003 , treatment 183, control 180, Cox regression.

risk of no virological cure, 39.0% lower , RR 0.61, p = 0.002 , treatment 14 of 183 (7.7%), control 36 of 180 (20.0%), adjusted, Cox regression.

Mahmud et al., 10/9/2020, Double Blind Randomized Controlled Trial, Bangladesh, South Asia, peer-reviewed, 15 authors, dosage 12mg single dose, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.

Submit Corrections or Comments In Silico Francés-Monerris et al., ChemRxiv, doi:10.26434/chemrxiv.12782258.v1 (Preprint) Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent Details In silico study showing that ivermectin is capable of interfering in different key steps of the SARS-CoV-2 replication cycle. Details Source PDF

In Silico

Francés-Monerris et al., ChemRxiv, doi:10.26434/chemrxiv.12782258.v1 (Preprint) Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent In silico study showing that ivermectin is capable of interfering in different key steps of the SARS-CoV-2 replication cycle.

Francés-Monerris et al., 10/8/2020, preprint, 8 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Late 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 Details Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10.. Details Source PDF

Late treatment study

Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint) 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 Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care.This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication.In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group.For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More than the total excess mortality happened on the first day. This is consistent with treated patients being in more serious condition, and with many of the control group patients being in hospital for something unrelated to COVID-19.Authors use a machine learning based propensity scoring system that appears over-parameterized and likely to result in significant overfitting and inaccurate results. Essentially they test for all interactions between two and three covariates. The nature and large number of covariates means many random correlations may be found. COVID-19 severity is not used.This study also does not compare treatments with a control group not receiving the treatment - authors put patients receiving treatments after 48 hours in the control group.Authors state that outcomes within 24 hours were excluded, however KM curves show significant mortality at day 1 (only for the treatment groups).Several protocol violations and missing data have also been reported in this study: [1, 2].See also: [3].Ivermectin dosage details: [4]

risk of death, 17.1% lower , RR 0.83, p = 0.01 , treatment 92 of 203 (45.3%), control 1438 of 2630 (54.7%), IVM vs. control day 43 (last day available) weighted KM from figure 3, per the pre-specified rules, the last available day mortality results have priority.

risk of death, 39.0% higher , RR 1.39, p = 0.16 , treatment 47 of 203 (23.2%), control 401 of 2630 (15.2%), adjusted, day 30, Table 2, IVM wHR.

Soto-Becerra et al., 10/8/2020, retrospective, database analysis, Peru, South America, preprint, median age 59.4, 4 authors, dosage 200μg/kg single dose.

Submit Corrections or Comments Late 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 Details Small RCT with 25 ivermectin and 25 control patients, not finding a significant difference in recovery at day 7. Details Source PDF

Late treatment study

Chachar et al., International Journal of Sciences, 9:31-35, doi:10.18483/ijSci.2378 (Peer Reviewed) Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients Small RCT with 25 ivermectin and 25 control patients, not finding a significant difference in recovery at day 7.

risk of no recovery at day 7, 10.0% lower , RR 0.90, p = 0.50 , treatment 9 of 25 (36.0%), control 10 of 25 (40.0%).

Chachar et al., 9/30/2020, Randomized Controlled Trial, India, South Asia, peer-reviewed, 6 authors, dosage 36mg, 12mg stat, 12mg after 12 hours, 12mg after 24 hours.

Submit Corrections or Comments Late Khan et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.08.007 (Letter) death, ↓87.0% , p Ivermectin treatment may improve the prognosis of patients with COVID-19 Details Retrospective 115 ivermectin patients and 133 control patients showing significantly lower death and faster viral clearance. Some potential issues and the authors' response can be found in [1, 2]. Details Source PDF

Late treatment study

Khan et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.08.007 (Letter) Ivermectin treatment may improve the prognosis of patients with COVID-19 Retrospective 115 ivermectin patients and 133 control patients showing significantly lower death and faster viral clearance.Some potential issues and the authors' response can be found in [1, 2].

risk of death, 87.0% lower , RR 0.13, p , treatment 1 of 115 (0.9%), control 9 of 133 (6.8%).

risk of ICU admission, 89.5% lower , RR 0.11, p = 0.007 , treatment 1 of 115 (0.9%), control 11 of 133 (8.3%).

time to viral-, 73.3% lower , relative time 0.27, p , treatment 115, control 133.

Khan et al., 9/24/2020, retrospective, Bangladesh, South Asia, preprint, median age 35.0, 8 authors, dosage 12mg single dose.

Submit Corrections or Comments In Vitro 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 Details In Vitro study showing Ivermectin is a safe wide-spectrum antiviral against SARS-CoV-2, human papillomavirus (HPV), Epstein–Barr virus (EBV), and HIV. Authors note that the combination of ivermectin and other drugs might result in more f.. Details Source PDF

In Vitro

Li et al., J. Cellular Physiology, doi:10.1002/jcp.30055 (Peer Reviewed) (In Vitro) Quantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment In Vitro study showing Ivermectin is a safe wide-spectrum antiviral against SARS-CoV-2, human papillomavirus (HPV), Epstein–Barr virus (EBV), and HIV.Authors note that the combination of ivermectin and other drugs might result in more favorable prognoses for patients with COVID‐19, for example ivermerctin and HCQ.

Li et al., 9/22/2020, peer-reviewed, 3 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Early Carvallo et al., Journal of Clinical Trials, 11:459 (preprint 9/15/20) (Peer Reviewed) death, ↓85.4% , p=0.08 Safety and Efficacy of the Combined Use of Ivermectin, Dexamethasone, Enoxaparin and Aspirina against COVID-19 the I.D.E.A. Protocol Details Prospective trial of ivermectin, dexamethasone, enoxaparin, and aspirin, showing no hospitalization for mild cases, and lower mortality for moderate/severe patients. Details Source PDF

Early treatment study

Carvallo et al., Journal of Clinical Trials, 11:459 (preprint 9/15/20) (Peer Reviewed) Safety and Efficacy of the Combined Use of Ivermectin, Dexamethasone, Enoxaparin and Aspirina against COVID-19 the I.D.E.A. Protocol Prospective trial of ivermectin, dexamethasone, enoxaparin, and aspirin, showing no hospitalization for mild cases, and lower mortality for moderate/severe patients.

moderate/severe patients, 85.4% lower , RR 0.15, p = 0.08 , treatment 1 of 32 (3.1%), control 3 of 14 (21.4%), the only treatment death was a patient already in the ICU before treatment.

Carvallo et al., 9/15/2020, prospective, Argentina, South America, peer-reviewed, mean age 55.7, 3 authors, dosage 36mg days 1, 8, dose varied depending on patient condition - mild 24mg, moderate 36mg, severe 48mg, this trial uses multiple treatments in the treatment arm (combined with dexamethasone, enoxaparin, and aspirin) - results of individual treatments may vary.

Submit Corrections or Comments Review 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? Details Review of ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2. Cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, V.. Details Source PDF

Review

Jans et al., Cells 2020, 9:9, 2100, doi:10.3390/cells9092100 (Review) (Letter) Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal? Review of ivermectin as a host-directed broad-spectrum antiviral agent for a range of viruses, including SARS-CoV-2.Cell culture experiments show robust antiviral action towards HIV-1, dengue virus (DENV), Zika virus, West Nile virus, Venezuelan equine encephalitis virus, Chikungunya virus, Pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19).

Jans et al., 9/15/2020, preprint, 2 authors.

Submit Corrections or Comments In SIlico Swargiary , A., Research Square, doi:10.21203/rs.3.rs-73308/v1 (Preprint) Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies Details In Silico study showing high binding affinity of ivermectin with SARS-CoV-2 RNA-dependent RNA polymerase, suggesting ivermectin as an inhibitor of RdRp. Details Source PDF

In SIlico

Swargiary , A., Research Square, doi:10.21203/rs.3.rs-73308/v1 (Preprint) Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a therapeutic drug against SARS-CoV2: Evidence from in silico studies In Silico study showing high binding affinity of ivermectin with SARS-CoV-2 RNA-dependent RNA polymerase, suggesting ivermectin as an inhibitor of RdRp.

Swargiary et al., 9/9/2020, preprint, 1 author.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Review 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 Details Review suggesting that ivermectin may be useful for late stage COVID-19. Authors note that ivermectin, in doses at or modestly above the standard clinical dose, may have important clinical potential for managing disorders associated with .. Details Source PDF

Review

DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2020-001350 (Review) (Peer Reviewed) Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19 Review suggesting that ivermectin may be useful for late stage COVID-19. Authors note that ivermectin, in doses at or modestly above the standard clinical dose, may have important clinical potential for managing disorders associated with life-threatening respiratory distress and cytokine storm, such as advanced COVID-19.

DiNicolantonio et al., 9/6/2020, peer-reviewed, 3 authors.

Submit Corrections or Comments Late 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 Details Small RCT with 32 ivermectin patients and 30 control patients. The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days vs. 6.33 ± 4.23 days in the control arm, p > 0.05. Negative PCR results were not signific.. Details Source PDF

Late treatment study

Podder et al., IMC J. Med. Science, 14:2, July 2020 (Peer Reviewed) Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study Small RCT with 32 ivermectin patients and 30 control patients.The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days vs. 6.33 ± 4.23 days in the control arm, p > 0.05.Negative PCR results were not significantly different between control and intervention arms, p>0.05. We are not sure what the results were because the abstract and Table 5 have switched the results.

recovery time from enrollment, 16.1% lower , relative time 0.84, p = 0.34 , treatment 32, control 30.

Podder et al., 9/3/2020, Randomized Controlled Trial, Bangladesh, South Asia, peer-reviewed, 4 authors, dosage 200μg/kg single dose.

Submit Corrections or Comments Late 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 Details Small RCT of hospitalized patients in India with 19 ivermectin patients and 13 control patients, with all receiving SOC including HCQ, showing no significant differences. The patient population is biased because the study recruited patien.. Details Source PDF

Late treatment study

Kishoria et al., Paripex - Indian Journal of Research, doi:10.36106/paripex/4801859 (Peer Reviewed) Ivermectin as adjuvant to hydroxychloroquine in patients resistant to standard treatment for SARS-CoV-2: results of an open-label randomized clinical study Small RCT of hospitalized patients in India with 19 ivermectin patients and 13 control patients, with all receiving SOC including HCQ, showing no significant differences. The patient population is biased because the study recruited patients that did not respond to standard treatment. Authors do not specify the treatment delay but it is likely relatively late because the patients had already undergone standard treatment. Criteria for discharge are not provided. The time of discharge status is not specified and may not have been an equal time since treatment initiation for all patients.Authors indicate 19 treatment and 16 control patients, but the results only show 13 control patients. Authors do not indicate why the other 3 are missing.Randomization in this small sample resulted in very large differences in the groups, with over twice as many in the ivermectin group with age >40, and the only 2 patients with age >60 both in the ivermectin group. Authors did not adjust for these differences.

risk of no hospital discharge, 7.5% higher , RR 1.08, p = 1.00 , treatment 11 of 19 (57.9%), control 7 of 13 (53.8%).

risk of no virological cure, 7.5% higher , RR 1.08, p = 1.00 , treatment 11 of 19 (57.9%), control 7 of 13 (53.8%), day 3.

risk of no virological cure, 220.0% higher , RR 3.20, p = 0.45 , treatment 1 of 5 (20.0%), control 0 of 6 (0.0%), continuity correction due to zero event, day 5.

Kishoria et al., 8/31/2020, Randomized Controlled Trial, India, South Asia, peer-reviewed, 7 authors, dosage 12mg single dose.

Submit Corrections or Comments PrEPPEP Shouman et al., Journal of Clinical and Diagnostic Research, doi:10.7860/JCDR/2020/46795.0000 (Peer Reviewed) symp. case, ↓91.3% , p Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt: A Randomised Clinical Trial Details PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group, adjusted odds ratio OR 0.087, p .. Details Source PDF

Prophylaxis study

Shouman et al., Journal of Clinical and Diagnostic Research, doi:10.7860/JCDR/2020/46795.0000 (Peer Reviewed) Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt: A Randomised Clinical Trial PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group, adjusted odds ratio OR 0.087, p NCT04422561. See also [1].

risk of symptomatic case, 91.3% lower , RR 0.09, p , treatment 15 of 203 (7.4%), control 59 of 101 (58.4%), adjusted, multivariate.

risk of COVID-19 severe case, 92.9% lower , RR 0.07, p = 0.002 , treatment 1 of 203 (0.5%), control 7 of 101 (6.9%), unadjusted.

Shouman et al., 8/28/2020, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 8 authors, dosage 18mg days 1, 3, dose varies depending on weight - 40-60kg: 15mg, 60-80kg: 18mg, >80kg: 24mg.

Submit Corrections or Comments Early Espitia-Hernandez et al., Biomedical Research, 31:5 (Peer Reviewed) viral+, ↓97.2% , p Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study Details Small study with 28 patients treated with ivermectin + AZ + cholecalciferol and 7 control patients. All treated patients were PCR- at day 10 while all control patients remained PCR+. The mean duration of symptoms was 3 days in the treatm.. Details Source PDF

Early treatment study

Espitia-Hernandez et al., Biomedical Research, 31:5 (Peer Reviewed) Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study Small study with 28 patients treated with ivermectin + AZ + cholecalciferol and 7 control patients.All treated patients were PCR- at day 10 while all control patients remained PCR+. The mean duration of symptoms was 3 days in the treatment group and 10 days in the control group.

risk of viral+ at day 10, 97.2% lower , RR 0.03, p , treatment 0 of 28 (0.0%), control 7 of 7 (100.0%), continuity correction due to zero event.

Espitia-Hernandez et al., 8/15/2020, retrospective, Mexico, North America, peer-reviewed, mean age 45.1, 5 authors, dosage 6mg days 1-2, 8-9, this trial uses multiple treatments in the treatment arm (combined with azithromycin and cholecalciferol) - results of individual treatments may vary.

Submit Corrections or Comments Late 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 Details Retrospective 148 hospitalized patients showing triple therapy with ivermectin + atorvastatin + N-acetylcysteine resulted in a 1.35% case fatality rate which was well below the national average. Details Source PDF

Late treatment study

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 Retrospective 148 hospitalized patients showing triple therapy with ivermectin + atorvastatin + N-acetylcysteine resulted in a 1.35% case fatality rate which was well below the national average.

Bhattacharya et al., 8/14/2020, peer-reviewed, mean age 57.6, 6 authors.

Submit Corrections or Comments Review 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 Details Panel review of ivermectin reporting that "ivermectin in the dose of 12mg BD alone or in combination with other therapy for 5–7 days may be considered as safe therapeutic option for mild moderate or severe cases of Covid-19 infection.. Details Source PDF

Review

Vora et al., Indian Journal of Tuberculosis, doi:10.1016/j.ijtb.2020.07.031 (Review) (Peer Reviewed) White paper on Ivermectin as a potential therapy for COVID-19 Panel review of ivermectin reporting that "ivermectin in the dose of 12mg BD alone or in combination with other therapy for 5–7 days may be considered as safe therapeutic option for mild moderate or severe cases of Covid-19 infection. It is cost effective especially when the other drugs are very costly & not easily available".

Vora et al., 7/31/2020, peer-reviewed, 4 authors.

Submit Corrections or Comments Late Chang et al., ResearchGate (Preprint) Post-acute or prolonged COVID-19: ivermectin treatment for patients with persistent symptoms or post-acute symptoms Details Report on 33 patients with persistent or post-acute symptoms treated with ivermectin, showing a high rate of clinical improvement. Details Source PDF

Late treatment study

Chang et al., ResearchGate (Preprint) Post-acute or prolonged COVID-19: ivermectin treatment for patients with persistent symptoms or post-acute symptoms Report on 33 patients with persistent or post-acute symptoms treated with ivermectin, showing a high rate of clinical improvement.

Chang et al., 7/31/2020, preprint, 4 authors.

Submit Corrections or Comments Theory 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 Details Proposed PEP protocol based on ivermectin. Details Source PDF

Theory

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

Chang et al., 7/31/2020, preprint, 2 authors.

Submit Corrections or Comments Late Alam et al., Journal of Bangladesh College of Physicians and Surgeons, doi:10.3329/jbcps.v38i0.47512 (Preprint) A Case Series of 100 COVID-19 Positive Patients Treated with Combination of Ivermectin and Doxycycline Details Case study of 100 patients treated with ivermectin and doxycycline, with no ICU admission, deaths, or serious side effects reported. Details Source PDF

Late treatment study

Alam et al., Journal of Bangladesh College of Physicians and Surgeons, doi:10.3329/jbcps.v38i0.47512 (Preprint) A Case Series of 100 COVID-19 Positive Patients Treated with Combination of Ivermectin and Doxycycline Case study of 100 patients treated with ivermectin and doxycycline, with no ICU admission, deaths, or serious side effects reported.

Alam et al., 7/31/2020, preprint, 4 authors.

Submit Corrections or Comments Late 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 Details Comparison of 200 patients treated with ivermectin + doxycycline and 200 treated with HCQ + AZ. The HCQ + AZ group had more severe cases at baseline. Viral clearance was faster with ivermectin + doxycycline. Ivermectin dose is given all o.. Details Source PDF

Late treatment study

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 Comparison of 200 patients treated with ivermectin + doxycycline and 200 treated with HCQ + AZ. The HCQ + AZ group had more severe cases at baseline. Viral clearance was faster with ivermectin + doxycycline. Ivermectin dose is given all on one day, whereas HCQ is given over 10 days and therapeutic levels may not be reached for several days.

Rahman et al., 7/31/2020, peer-reviewed, 6 authors.

Submit Corrections or Comments Early 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 Details Small 116 patient RCT with low-risk patients comparing ivermectin+doxycycline and HCQ+AZ, showing lower hospitalization, higher viral clearance, and faster symptom resolution and viral clearance with ivermectin+doxycycline. Mid-recovery r.. Details Source PDF

Early treatment study

Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 (Peer Reviewed) A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients Small 116 patient RCT with low-risk patients comparing ivermectin+doxycycline and HCQ+AZ, showing lower hospitalization, higher viral clearance, and faster symptom resolution and viral clearance with ivermectin+doxycycline. Mid-recovery resolution of symptoms is statistically significantly better with treatment, while other measures do not reach statistical significance. Instructions were to take ivermectin on an empty stomach, reducing lung tissue concentration.

risk of hospitalization, 80.6% lower , RR 0.19, p = 0.23 , treatment 0 of 60 (0.0%), control 2 of 56 (3.6%), continuity correction due to zero event.

risk of no recovery, 46.4% lower , RR 0.54, p , treatment 27 of 60 (45.0%), control 47 of 56 (83.9%), mid-recovery day 5.

recovery time, 15.2% lower , relative time 0.85, p = 0.07 , treatment 60, control 56.

risk of no virological cure, 80.6% lower , RR 0.19, p = 0.23 , treatment 0 of 60 (0.0%), control 2 of 56 (3.6%), continuity correction due to zero event.

time to viral-, 4.3% lower , relative time 0.96, p = 0.23 , treatment 60, control 56.

Chowdhury et al., 7/14/2020, Randomized Controlled Trial, Bangladesh, South Asia, peer-reviewed, 6 authors, dosage 200μg/kg single dose, this trial compares with another treatment - results may be better when compared to placebo, this trial uses multiple treatments in the treatment arm (combined with doxycycline) - results of individual treatments may vary.

Submit Corrections or Comments Late 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) Details Small trial of hospitalized patients with 16 of 87 patients being treated with ivermectin showing a significantly lower mean hospital stay with ivermectin: 7.62 vs. 13.22 days, p=0.00005. 0 of 16 ivermectin patients died vs. 2 of 71 cont.. Details Source PDF

Late treatment study

Gorial et al., medRxiv, doi:10.1101/2020.07.07.20145979 (Preprint) Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial) Small trial of hospitalized patients with 16 of 87 patients being treated with ivermectin showing a significantly lower mean hospital stay with ivermectin: 7.62 vs. 13.22 days, p=0.00005.0 of 16 ivermectin patients died vs. 2 of 71 control patients.

risk of death, 71.0% lower , RR 0.29, p = 1.00 , treatment 0 of 16 (0.0%), control 2 of 71 (2.8%), continuity correction due to zero event.

hospitalization time, 42.0% lower , relative time 0.58, p , treatment 16, control 71.

Gorial et al., 7/8/2020, retrospective, Iraq, Middle East, preprint, 9 authors, dosage 200μg/kg single dose.

Submit Corrections or Comments In Silico Lehrer et al., In Vivo, 34:5, 3023-3026, doi:10.21873/invivo.12134 Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2 Details In silico analysis showing ivermectin docking which may interfere with the attachment of the spike to the human cell membrane. Details Source PDF

In Silico

Lehrer et al., In Vivo, 34:5, 3023-3026, doi:10.21873/invivo.12134 Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2 In silico analysis showing ivermectin docking which may interfere with the attachment of the spike to the human cell membrane.

Lehrer et al., 6/19/2020, preprint, 2 authors.

In Silico studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments Early Ramos et al., Preprint (Preprint) Intervención de la Ivermectina Pre-Hospitalaria para la Modificación de la Evolución del Covid19. Estudio realizado en Perú Details Prospective study of 63 outpatients in Peru treated with ivermectin, reporting significant improvement within 24 hours. Details Source PDF

Early treatment study

Ramos et al., Preprint (Preprint) Intervención de la Ivermectina Pre-Hospitalaria para la Modificación de la Evolución del Covid19. Estudio realizado en Perú Prospective study of 63 outpatients in Peru treated with ivermectin, reporting significant improvement within 24 hours.

Ramos et al., 6/16/2020, preprint, 9 authors.

Submit Corrections or Comments Review 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 Details Review of the antimicrobial, antiviral, and anti-cancer properties of ivermectin. Antiviral effects have been reported for Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki For.. Details Source PDF

Review

Heidary et al., The Journal of Antibiotics, 73, 593–602, doi:10.1038/s41429-020-0336-z (Review) (Peer Reviewed) Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen Review of the antimicrobial, antiviral, and anti-cancer properties of ivermectin.Antiviral effects have been reported for Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.

Heidary et al., 6/12/2020, peer-reviewed, 2 authors.

Submit Corrections or Comments Dosing Arshad et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.1909 (Peer Reviewed) (Dosing) dosing study Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics Details Pharmacokinetic analysis predicting that ivermectin will achieve lung concentration over 10 times higher than the reported EC50. Details Source PDF

Dosing

Arshad et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.1909 (Peer Reviewed) (Dosing) Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics Pharmacokinetic analysis predicting that ivermectin will achieve lung concentration over 10 times higher than the reported EC50.

Arshad et al., 5/20/2020, peer-reviewed, 22 authors.

Submit Corrections or Comments Early 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 Details Peru observational case study of 7 patients treated with ivermectin, showing improvement and resolution of fever within 48 hours, and 100% recovery. Details Source PDF

Early treatment study

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 Peru observational case study of 7 patients treated with ivermectin, showing improvement and resolution of fever within 48 hours, and 100% recovery.

Chang et al., 5/2/2020, preprint, 1 author.

Submit Corrections or Comments Review 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 Details Responses to Caly et al., and the author's reply. The original authors note that "ivermectin's key direct target in mammalian cells is a not a viral component, but a host protein important in intracellular transport; the fact that it.. Details Source PDF

Review

Bray et al., Antiviral Res., doi:10.1016/j.antiviral.2020.104805 (Review) (Preprint) Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses Responses to Caly et al., and the author's reply. The original authors note that "ivermectin's key direct target in mammalian cells is a not a viral component, but a host protein important in intracellular transport; the fact that it is a host-directed agent (HDA) is almost certainly the basis of its broad-spectrum activity against a number of different RNA viruses in vitro. The way a HDA can reduce viral load is by inhibiting a key cellular process that the virus hijacks to enhance infection by suppressing the host antiviral response. Reducing viral load by even a modest amount by using a HDA at low dose early in infection can be the key to enabling the body's immune system to begin to mount the full antiviral response before the infection takes control."

Bray et al., 4/21/2020, preprint, 5 authors.

Submit Corrections or Comments In Vitro 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 Details In Vitro study showing that ivermectin is an inhibitor of SARS-CoV-2, with a single addition to Vero-hSLAM cells 2h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48h. Some people claim this study show.. Details Source PDF

In Vitro

Caly et al., Antiviral Research, doi:10.1016/j.antiviral.2020.104787 (Peer Reviewed) (In Vitro) The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro In Vitro study showing that ivermectin is an inhibitor of SARS-CoV-2, with a single addition to Vero-hSLAM cells 2h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48h.Some people claim this study shows that therapeutic concentrations cannot be reached in humans, however this is incorrect. The authors explain why using this in vitro study to determine the effective dose in vivo is a fallacy in this presentation [1]. Authors indicate that the concentration required is very unlikely to be an issue. The study used monkey kidney cells (the only choice at the time of the experiments), which they note lack adaptive immune responses and do not produce interferon. Authors also note that ivermectin accumulates in lung and other tissues, and that the average lung concentration shown in modeling studies exceeds the effective level in their study. Authors have also repeated experiments with human lung cells showing 6-8 times improved IC50.Author's have also responded noting that "ivermectin's key direct target in mammalian cells is a not a viral component, but a host protein important in intracellular transport; the fact that it is a host-directed agent (HDA) is almost certainly the basis of its broad-spectrum activity against a number of different RNA viruses in vitro. The way a HDA can reduce viral load is by inhibiting a key cellular process that the virus hijacks to enhance infection by suppressing the host antiviral response. Reducing viral load by even a modest amount by using a HDA at low dose early in infection can be the key to enabling the body's immune system to begin to mount the full antiviral response before the infection takes control." Authors note that ivermectin works with the immune system and a 1:1 ratio of drug to virus is unlikely to be required [2].In further research, authors note that they find efficacy for prophylactic use, and that smaller repeated doses is more efffective than a single larger dose [3].Rajter et al. summarize the author, noting that “the antiviral activities of ivermectin have been derived from laboratory experiments that largely involve high, generally non physiologic, multiplicities of infection, and cell mono layer cultures, often of cell lines such as Vero cells that are not clinically relevant. The EC50 values should not be interpreted beyond the fact that they reveal robust, dose dependent antiviral activity in the cell model system used, and it would be naive to strive for μM concentrations of ivermectin in the clinic based on them.” [4].

Caly et al., 4/3/2020, peer-reviewed, 5 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

Submit Corrections or Comments 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 Details Safety study concluding that ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose. Adverse effects were similar between ivermectin and placebo and di.. Details Source PDF

N/A

Guzzo et al., J. Clinical Pharmacology, doi:10.1177/009127002237994 (Peer Reviewed) Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects Safety study concluding that ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA-approved dose. Adverse effects were similar between ivermectin and placebo and did not increase with dose. Authors also show that the plasma concentration is much higher when taken with food (geometric mean AUC 2.6 times higher).

Guzzo et al., 1/1/2013, peer-reviewed, 9 authors.

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