Ivermectin for COVID-19: real-time analysis of all 97 studies

Covid Analysis (Preprint) (meta analysis)

Ivermectin for COVID-19: real-time meta analysis of 60 studies

• 95% of 39 early treatment and prophylaxis studies report positive effects (93% of all 60 studies). 28 studies show statistically significant improvements in isolation.

• Random effects meta-analysis with pooled effects using the most serious outcome reported shows 76% and 85% improvement for early treatment and prophylaxis (RR 0.24 [0.14-0.41] and 0.15 [0.09-0.25]). Results are similar after exclusion based sensitivity analysis: 78% and 87% (RR 0.22 [0.16-0.31] and 0.13 [0.07-0.25]), and after restriction to 35 peer-reviewed studies: 77% and 88% (RR 0.23 [0.14-0.38] and 0.12 [0.05-0.30]).

• 81% and 96% lower mortality is observed for early treatment and prophylaxis (RR 0.19 [0.07-0.54] and 0.04 [0.00-0.58]). Statistically significant improvements are seen for mortality, ventilation, hospitalization, cases, and viral clearance.

• 95% of the 19 Randomized Controlled Trials (RCTs) for early treatment and prophylaxis report positive effects, with an estimated improvement of 69% and 83% respectively (RR 0.31 [0.23-0.43] and 0.17 [0.05-0.61]), and 90% of all 31 RCTs.

• The probability that an ineffective treatment generated results as positive as the 60 studies to date is estimated to be 1 in 2 trillion (p = 0.00000000000045).

• Heterogeneity arises from many factors including treatment delay, patient population, the effect measured, variants, and treatment regimens. The consistency of positive results across a wide variety of cases is remarkable. Heterogeneity is low in specific cases, for example early treatment mortality.

• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 27% 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. Not doing so increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage.

• Many studies do not specify administration, or specify fasting. Administration with food may significantly increase plasma and tissue concentration.

• All data to reproduce this paper and the sources are in the appendix. See [Bryant, Hariyanto, Hill, Kory, Lawrie, Nardelli] for other meta analyses, all with similar results confirming effectiveness.

	Improvement	Studies	Authors	Patients
Early treatment	76% [59‑86%]	25	266	3,382
Late treatment	46% [29‑59%]	21	175	6,760
Prophylaxis	85% [75‑91%]	14	108	8,789
Mortality	70% [53‑81%]	22	205	7,690
RCTs only	64% [49‑74%]	31	340	5,316
All studies	71% [62‑77%]	60	549	18,931

Evidence base used for other COVID-19 approvals
Medication	Studies	Patients	Improvement
Budesonide (UK)	1	1,779	17%
Remdesivir (USA)	1	1,063	31%
Casiri/imdevimab (USA)	1	799	66%
Ivermectin evidence	60	18,931	71% [62‑77%]

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.

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.

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.

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 < 0.001, 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, Middle East, peer-reviewed, 7 authors.

Hariyanto et al., Reviews In Medical Virology, doi:10.1002/rmv.2265 (Peer Reviewed)

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.

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, Middle East, peer-reviewed, 16 authors, dosage 12mg days 1-3.

Roman et al., medRxiv, doi:10.1101/2021.05.21.21257595 (Preprint) (meta analysis)

Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials

Severely flawed meta analysis, incorrect at first glance.

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 report 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.

For additional errors, see [1].

Only one of these errors has been partially fixed 4 days later - the Niaee RR was corrected, but the associated conclusion was not. Other errors have not been corrected.

[1] pubpeer.com/publications/955418F3D4D39742CFFA8C1B023AA3

Roman et al., 5/25/2021, preprint, 6 authors.

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.

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.

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.

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.

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.

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.

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 < 0.001, model 7, same time period, patients receiving kit.

risk of hospitalization, 68.4% lower, RR 0.32, p < 0.001, 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.

Kory et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001377 (Review) (Peer Reviewed) (meta analysis)

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.

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, Middle East, 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.

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.

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.

Morgenstern et al., medRxiv, doi:10.1101/2021.04.10.21255248 (Preprint)

Retrospective cohort study of Ivermectin as a SARS-CoV-2 pre-exposure prophylactic method in Healthcare Workers

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. 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, preprint, 16 authors, dosage 200μg/kg weekly.

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.

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.

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.

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 < 0.001, 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.

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.

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.

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.

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, Africa, preprint, 3 authors, dosage 200μg/kg, dose varied, typically 150-200μg/kg.

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.

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.

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.

[1] twitter.com/Covid19Crusher/status/1367854845340844039

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.

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].

[1] en.wikipedia.org/wiki/Satoshi_%C5%8Cmura

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

Emmerich et al., Int. J. Environ. Res. Public Health, doi:10.3390/ijerph18073371 (Peer Reviewed)

Comparisons between the Neighboring States of Amazonas and Pará in Brazil in the Second Wave of COVID-19 Outbreak and a Possible Role of Early Ambulatory Treatment

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, peer-reviewed, 1 author.

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.

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.