Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines

Background:

INTRODUCTION

To date, very few treatments have been demonstrated to reduce the burden of morbidity and mortality from COVID-19. Although corticosteroids have been proven to reduce mortality in severe disease,¹ there has been little convincing evidence on interventions that may prevent disease, reduce hospitalizations, and reduce the numbers of people progressing to critical disease and death.

Ivermectin is a well-known medicine that is approved as an antiparasitic by the World Health Organization and the US Food and Drug Administration. It is widely used in low- and middle-income countries (LMICs) to treat worm infections.^2,3 Also used for the treatment of scabies and lice, it is one of the World Health Organization’s Essential Medicines.⁴ With total doses of ivermectin distributed apparently equaling one-third of the present world population,⁵ ivermectin at the usual doses (0.2–0.4 mg/kg) is considered extremely safe for use in humans.^6,7 In addition to its antiparasitic activity, it has been noted to have antiviral and anti-inflammatory properties, leading to an increasing list of therapeutic indications.⁸

Since the start of the SARS-CoV-2 pandemic, both observational and randomized studies have evaluated ivermectin as a treatment for, and as prophylaxis against, COVID-19 infection. A review by the Front Line COVID-19 Critical Care Alliance summarized findings from 27 studies on the effects of ivermectin for the prevention and treatment of COVID-19 infection, concluding that ivermectin “demonstrates a strong signal of therapeutic efficacy” against COVID-19.⁹ Another recent review found that ivermectin reduced deaths by 75%.¹⁰ Despite these findings, the National Institutes of Health in the United States recently stated that “there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19,”¹¹ and the World Health Organization recommends against its use outside of clinical trials.¹²

Ivermectin has exhibited antiviral activity against a wide range of RNA and some DNA viruses, for example, Zika, dengue, yellow fever, and others.¹³ Caly et al¹⁴ demonstrated specific action against SARS-CoV-2 in vitro with a suggested host-directed mechanism of action being the blocking of the nuclear import of viral proteins^14,15 that suppress normal immune responses. However, the necessary cell culture EC₅₀ may not be achievable in vivo.¹⁶ Other conjectured mechanisms include inhibition of SARS-CoV-2 3CLPro activity^17,18 (a protease essential for viral replication), a variety of anti-inflammatory effects,¹⁹ and competitive binding of ivermectin with the viral S protein as shown in multiple in silico studies.²⁰ The latter would inhibit viral binding to ACE-2 receptors suppressing infection. Hemagglutination via viral binding to sialic acid receptors on erythrocytes is a recently proposed pathologic mechanism²¹ that would be similarly disrupted. Both host-directed and virus-directed mechanisms have thus been proposed, the clinical mechanism may be multimodal, possibly dependent on disease stage, and a comprehensive review of mechanisms of action is warranted.

Developing new medications can take years; therefore, identifying existing drugs that can be repurposed against COVID-19 that already have an established safety profile through decades of use could play a critical role in suppressing or even ending the SARS-CoV-2 pandemic. Using repurposed medications may be especially important because it could take months, possibly years, for much of the world’s population to get vaccinated, particularly among LMIC populations.

Currently, ivermectin is commercially available and affordable in many countries globally.⁶ A 2018 application for ivermectin use for scabies gives a direct cost of $2.90 for 100 12-mg tablets.²² A recent estimate from Bangladesh²³ reports a cost of US$0.60—US$1.80 for a 5-day course of ivermectin. For these reasons, the exploration of ivermectin’s potential effectiveness against SARS-CoV-2 may be of particular importance for settings with limited resources.²⁴ If demonstrated to be effective as a treatment for COVID-19, the cost-effectiveness of ivermectin should be considered against existing treatments and prophylaxes.

The aim of this review was to assess the efficacy of ivermectin treatment among people with COVID-19 infection and as a prophylaxis among people at higher risk of COVID-19 infection. In addition, we aimed to prepare a brief economic commentary (BEC) of ivermectin as treatment and as prophylaxis for COVID-19.²⁵

METHODS

The conduct of this review was guided by a protocol that was initially written using Cochrane’s rapid review template and subsequently expanded to a full protocol for a comprehensive review.²⁶

RESULTS

Search results and risk-of-bias assessment

The combined and preliminary deduplicated total was n = 583. We also identified 11 records from other sources (reference lists, etc). See PRISMA flow diagram for inclusion and exclusion details of these references (Figure ​(Figure11).

FIGURE 1.

Study flow diagram from search on 25 April 2021.

The supplementary search for the BEC identified 17 studies, of which 4 were retrieved in full. No full trial- or model-based economic evaluations (cost–utility analyses, cost–effectiveness analyses, or cost–benefit analyses) were identified.

Twenty-one trials in treatment and 2 trials in prophylaxis of COVID-19 met review inclusion. One further study⁴⁷ reported separate treatment and prophylaxis components; we label this study “Elgazzar” under both questions. In effect, there were 22 trials in treatment and 3 in prophylaxis. All of these contributed data to at least one review outcome and meta-analysis. Fifteen trials contributed data for the primary outcome for ivermectin treatment (death); 3 studies reported the primary outcome for prophylaxis (COVID-19 infection). Characteristics of included studies are given in Table ​Table1.1. Seventeen studies^47–63 were excluded as they were not RCTs and we identified 39 ongoing studies^64–102 and 2 studies^103,104 are awaiting classification.

Table 1.

Summary of study characteristics.

Study ID	Country	Design	Funding	Participants	Sample size	Ivermectin dose and frequency*	Comparator	Origin of data	Main outcomes reported
COVID-19 treatment studies
Ahmed 202023	Bangladesh	Double-blind	BPL(Pharma); Bangladesh, Canada, Sweden, and UK govt	Mild to moderate COVID (inpatients)	72	12 mg × 1 day or × 5 days (3 study arms)*	Placebo	Published in PR journal; emailed/responded with data	Time to viral clearance (PCR –ve), remission of fever and cough within 7 days, duration of hospitalization, mortality, failing to maintain sats >93%, adverse events, PCR –ve at 7 and 14 days
Babalola 2020105	Nigeria	Double-blind	Self-funded	Asymptomatic, mild or moderate COVID (45 inpatients and 17 outpatients)	62	6 mg every 84 hrs × 2 wks (arm 1) or 12 mg every 84 hrs × 2 wks (arm 2)	Ritonavir/lopinavir	MedRxiv preprint: emailed/responded with data. Paper accepted for publication	Time to PCR –ve, laboratory parameters (platelets, lymphocytes, clotting time), clinical symptom parameters
Bukhari 2021135	Pakistan	Open-label	None reported	Mild to moderate COVID (inpatients)	100	12 mg × 1 dose	SOC	MedRxiv preprint	Viral clearance, any adverse side effects, mechanical ventilation
Chaccour 202024	Spain	Double-blind	Idapharma, ISGlobal, and the University of Navarra	Mild COVID (outpatients)	24	0.4 mg/kg × 1 dose	Placebo	Published in PR journal	PCR +ve at day 7, proportion symptomatic at day 4,7,14,21, progression, death, adverse events
Chachar 2020112	Pakistan	Open-label	Self-funded	Mild COVID (outpatients)	50	12 mg at 0, 12, and 24 hours (3 doses)	SOC	Published in PR journal	Symptomatic at day 7
Chowdhury 2020136	Bangladesh	Quasi-RCT	None reported	Outpatients with a +ve PCR (approx. 78% symptomatic)	116	0.2 mg/kg x1 dose*	HCQ 400 mg 1st day then 200 mg BID × 9 days + AZM 500 mg daily × 5 days	Research square preprint	Time to –ve PCR test; period to symptomatic recovery; adverse events
Elgazzar 202047	Egypt	RCT	None reported	Mild to severe COVID (inpatients)	200	0.4 mg/kg daily × 4 days	HCQ 400 mg BID × 1 day then 200 mg BID × 9 days	Research square preprint: emailed/responded with data	Improved, progressed, died. Also measured CRP, D-dimers, HB, lymphocyte, serum ferritin after one week of treatment
Fonseca 202144	Brazil	Double-blind	Institution-funded	Moderate to severe (inpatients)	167	14 mg daily × 3 days (plus placebos × 2 additional days)	HCQ—400 mg BID on day 0 then daily × 4 days; CQ -450 mg BID day 0 then daily × 4 days	Prepublication data/manuscript in progress obtained via email	Death, invasive mechanical ventilation
Gonzalez 2021137	Mexico	Double-blind	Institution-funded	Moderate to severe (inpatients)	108	12 mg × 1 dose	Placebo	MedRxiv preprint	Length of hospital stay, invasive mechanical ventilation, death, time to negative PCR
Hashim 2020138	Iran	Quasi-RCT	None reported	Mild to critical (inpatients)	140	0.2 mg/kg × 2 days* Some had a 3rd dose a week later	SOC	MedRxiv preprint	Death, mean time to recovery, disease progression (deterioration)
Krolewiecki 2020106	Argentina	Open-label	None reported	Mild to moderate (inpatients)	45	0.6 mg/kg/d × 5 days	Placebo	Research Gate and SSRN preprints	Viral load reduction in respiratory secretions day 5, IVM concentrations in plasma, severe adverse events
Lopez-Medina 202185	Columbia	Double-blind	Institution-funded	Mild (outpatients)	476	0.3 mg/kg elixir × 5 days	Placebo	Published in a PR journal	Resolution of symptoms within 21 days, deterioration, clinical condition, hospitalization, adverse events
Mahmud 2020107	Bangladesh	Double-blind	None reported	Mild to moderate COVID (inpatients)	363	12 mg × 1 dose*	Placebo + SOC	Data published on clinical trial registry and clarification obtained via email	Improvement, deterioration, late clinical recovery, persistent PCR test +ve
Mohan 2021110	India	Double-blind	Institution-funded	Mild to moderate	152	12 mg or 24 mg elixir × 1 dose	Placebo	MedRxiv preprint research	Conversion of RT-PCR to negative result, decline of viral load at day 5 from enrollment
Niaee 2020108	Iran	Double-blind	Institution-funded	Mild to severe COVID	180	0.2 mg/kg × 1 and 3 other dosing options) ∼ 14 mg tablet†	Placebo	Research Square preprint	Deaths, length of stay, biochemical parameters
Okumus 2021115	Turkey	Quasi-RCT	None reported	Severe COVID	66	0.2 mg/kg × 5 days	SOC	Prepublication data/manuscript in progress obtained via email	Clinical improvement, deterioration, death, SOFA scores
Petkov 2021139	Bulgaria	Double-blind	Pharma-funded	Mild to moderate COVID	100	0.4 mg/kg × 3 days	Placebo	Prepublication data obtained from another source	Rate of conversion to PCR negative
Podder 2020140	Bangladesh	Open-label	Self-funded	Mild to moderate (outpatients)	62	0.2 mg/kg × 1 dose	SOC	Published in PR journal	Duration of symptoms, recovery time to symptom free from enrollment, recovery time to symptom free from symptom onset, repeat PCR result on day 10
Raad 2021113	Lebanon	Double-blind	Self-funded	Asymptomatic outpatients	100	9 mg PO if 45 kg–64 kg, 12 mg PO if 65 kg–84 kg and 0.15 mg/kg if body weight ≥85 kg	Placebo	Prepublication data/manuscript in progress obtained via email	Viral load reduction, hospitalization, adverse effects
Ravikirti 2021109	India	Double-blind	Self-funded	Mild to moderate COVID (inpatients)	112	12 mg × 2 days + SOC	Placebo + SOC	Published in PR journal	A negative RT-PCR report on day 6, symptomatic on day 6, discharge by day 10, admission to ICU, need for invasive mechanical ventilation, mortality
Rezai 2020111	Iran	Double-blind	None reported	Mild to moderate (inpatient)	60	0.2 mg/kg × 1 dose	SOC	Prepublication data obtained from another source	Clinical symptoms, respiratory rate and O2 saturation
Schwartz 2021114,141	Israel	Double-blind	None reported	Mild to moderate (outpatients)	94	0.15–0.3 mg/kg × 3 days	Placebo	Prepublication data obtained from another source	Viral clearance at day 4, 6, 8 and 10), hospitalization
COVID-19 prophylaxis studies
Chahla 2021142	Argentina	Open-label	None reported	Health care workers	234	12 mg (in drops) weekly + iota-carrageenan 6 sprays daily × 4 wk	SOC	Prepublication data/manuscript in progress obtained via email	COVID-19 infection (not clear if measured by PCR or symptoms)
Elgazzar 202047	Egypt	Open-label	Self-funded	Health care and family contacts	200	0.4 mg/kg, weekly × 2 weeks	SOC	Research square preprint: emailed/responded with data	Positive PCR test
Shouman 2020143	Egypt	Open-label	Self-funded	Family contacts	304	2 doses (15–24 mg depending on weight) on day 1 and day 3	SOC	Published in PR journal	Symptoms and/or positive COVID-19 PCR test within 14 days; adverse events

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^*Also administered doxycycline.

^†multiarm trial.

SOC, standard of care; PR, peer review.

A risk-of-bias summary graph is given in Figure ​Figure2.2. Eleven studies^{23,24,44,47,105,106–111} used satisfactory random sequence generation and allocation concealment. Two trials described satisfactory sequence generation, but it was unclear whether allocation was concealed.^112,113

FIGURE 2.

Risk-of-bias summary: review authors’ judgments about each risk of bias item for each included study.

Ten trials reported adequate blinding of the participants/personnel and/or the outcome assessors.^{23,24,44,105,107,109,110,111,113,114} The others were either unclear or high risk for blinding. We considered blinding to be a less important criterion for evaluation of evidence related to the review’s primary outcomes, namely death and laboratory-confirmed COVID-19 infection, which are objective outcomes.

We did not consider publication on preprint web sites to constitute a risk of bias because all studies were scrutinized and peer reviewed by us during the review process and, where additional information was needed, we contacted the authors for clarification.

Certainty of the evidence for all-cause mortality

Overall, death from any cause, taking into account all composite analyses, was judged to provide moderate-certainty evidence (SoF Table ​Table22 and Figures ​Figures44–11). A funnel plot corresponding to the primary outcome of death from any cause did not seem to suggest any evidence of publication bias (Figure ​(Figure7).7). Furthermore, the ease with which trial reports can be uploaded as preprints should reduce this risk.

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FIGURE 4.

Death due to any cause, excluding an outlier study responsible for the heterogeneity.

FIGURE 7.

Funnel plot of ivermectin versus control for COVID-19 treatment for all-cause death (subgrouped by severity).

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FIGURE 5.

Death due to any cause, excluding high risk-of-bias studies.

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FIGURE 6.

Death due to any cause, excluding studies with active controls.

Secondary outcomes

Secondary outcomes provided low to very low certainty evidence (SoF Table ​Table2).2). Low-certainty findings suggested that there may be no benefit with ivermectin for “need for mechanical ventilation,” whereas effect estimates for “improvement” and “deterioration” favored ivermectin but were graded as low certainty due to study design limitations and inconsistency (Figures ​(Figures1212–14). All other secondary outcome findings were assessed as very low certainty.

FIGURE 12.

Need for mechanical ventilation.

FIGURE 14.

Deterioration.

FIGURE 13.

Improvement.

Meta-analysis of 11 trials, assessing 1533 participants, found that there was no significant difference between ivermectin and control in the risk of severe adverse events (aRR 1.65, 95% CI 0.44–6.09; I² = 0%; low certainty evidence, downgraded for imprecision and study design limitations). Seven severe adverse events were reported in the ivermectin group and 2 in controls. The SAEs were as follows: 2 patients in the Mahmud trial¹⁰⁷ had esophagitis (this is a known side effect of doxycycline, which was coadministered with ivermectin in this trial); one patient in the study by Krolewiecki et al¹⁰⁶ had hyponatremia (this trial used high-dose ivermectin for 5 days); and 2 patients in a study from Turkey¹¹⁵ had serious “delirium-like behavior, agitation, aggressive attitude, and altered state of consciousness,” which the authors attributed to metabolic insufficiencies in MDR-1/ABCB1 or CYP3A4 genes, screening for which was a study feature. In the Lopez-Medina et al⁸⁵ trial, there were 2 SAEs in each arm (SoF Table ​Table22).

Ivermectin prophylaxis versus no ivermectin prophylaxis

Three studies involving 738 participants evaluated ivermectin for COVID-19 prophylaxis among health care workers and COVID-19 contacts. Meta-analysis of these 3 trials, assessing 738 participants, found that ivermectin prophylaxis among health care workers and COVID-19 contacts probably reduces the risk of COVID-19 infection by an average of 86% (79%–91%) (3 trials, 738 participants; aRR 0.14, 95% CI 0.09–0.21; 5.0% vs. 29.6% contracted COVID-19, respectively; low-certainty evidence; downgraded due to study design limitations and few included trials) (Figure ​(Figure15).15). In 2 trials involving 538 participants, no severe adverse events were recorded (SoF Table ​Table44).

FIGURE 15.

COVID-19 infection (prophylaxis studies).

Table 4.

Summary of findings table of ivermectin versus no ivermectin for COVID-19 prophylaxis in healthy population (people without COVID-19 infection).

Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	No ivermectin	Ivermectin
COVID-19 infection	296 per 1000	245 fewer infections per 1000 (234–269)	RR = 0.14 (0.09–0.21)	738 (3)	Low†
Admission to hospital	Not reported
Death from any cause	Not reported
Serious adverse events	No events occurred in 538 participants (2 studies), therefore the effect could not be estimated.

GRADE working group grades of evidence; High quality: Further research is very unlikely to change our confidence in the estimate of effect; Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; Very low quality: We are very uncertain about the estimate.

^*The basis for the assumed risk (eg, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

^†Downgraded −2 for study design limitations.

NNT, number needed to treat.

DISCUSSION

The findings indicate with moderate certainty that ivermectin treatment in COVID-19 provides a significant survival benefit. Our certainty of evidence judgment was consolidated by the results of trial sequential analyses, which show that the required IS has probably already been met. Low-certainty evidence on improvement and deterioration also support a likely clinical benefit of ivermectin. Low-certainty evidence suggests a significant effect in prophylaxis. Overall, the evidence also suggests that early use of ivermectin may reduce morbidity and mortality from COVID-19. This is based on (1) reductions in COVID-19 infections when ivermectin was used as prophylaxis, (2) the more favorable effect estimates for mild to moderate disease compared with severe disease for death due to any cause, and (3) on the evidence demonstrating reductions in deterioration.

The evidence on severe adverse events in this review was graded as low certainty, partly because there were too few events to reach statistical significance. Evidence from a recent systematic review of ivermectin use among people with parasitic infections suggests that ivermectin administered at the usual doses (0.2 or 0.4 mg/kg) is safe and could be safe at higher doses.^7,116 A recent World Health Organization document on ivermectin use for scabies found that adverse events with ivermectin were primarily minor and transient.²²

We restricted the included studies to the highest level of evidence, that is, RCTs, as a policy. This was despite there being numerous observational but nonrandomized trials of ivermectin, which one could argue could also be considered in an emergency. We included preprint and unpublished data from completed but not yet published trials due to the urgency related to evidence synthesis in the context of a global pandemic.¹¹⁷ Although there is the potential for selective reporting of outcomes and publication bias, we have factored in these considerations in interpreting results and forming conclusions. We adhered to PRISMA guidelines and the WHO statement on developing global norms for sharing data and results during public health emergencies.¹¹⁷

There are a number of limitations with this review. Several of the studies contributing data did not provide full descriptions of methods, so assessing risk of bias was challenging. Where descriptions of study methods were sparse or unclear, we attempted to contact authors to clarify methods, but lack of information led us to downgrade findings in several instances. Overall interpretation of findings was hampered due to variability in the participants recruited, treatment regimen, and the care offered to those in control groups. We have tried to take this variation into account through subgroup and sensitivity analyses. Nevertheless, dosing and treatment regimens and the use of ivermectin with other components of “standard care” require further research. We did not include laboratory outcome measures, such as viral clearance. The latter and other biochemical outcomes have been reported in several studies and reviews and tend to favor ivermectin.^{10,47,105,108} Several trials reported continuous data, such as length of hospital stay, as medians and interquartile ranges; therefore, we were unable to include these data in meta-analysis. Because we did not undertake in our protocol to perform narrative evidence synthesis, and because these data tended to favor ivermectin, the certainty of the effects of ivermectin on these continuous outcomes may be underestimated.

At least 5 other reviews of ivermectin use for COVID-19 have been published, including one coauthored with Nobel Laureate Professor Satoshi Ōmura, discoverer of ivermectin,^{9,10,118,119,120} but only 3 have been peer-reviewed^9,118,120 and only 2 attempt full systematic review.^10,119 We applied AMSTAR 2,¹²¹ a critical appraisal tool for systematic reviews of health care interventions, to the 2 nonpeered systematic reviews^10,119 and both were judged to be of low quality (Table ​(Table5).5). However, there was also a suggestion that ivermectin reduced the risk of death in treatment of COVID-19 in these reviews.

The recently updated WHO therapeutics guidelines¹² included 7 trials and 1419 people in the analysis of mortality. Reporting a risk reduction of 81% (odds ratio 0.19, 95% CI 0.09–0.36), the effect estimate favoring ivermectin was downgraded by 2 levels for imprecision, although the justification for this is unclear as the reported CI is precise (64%–91%).

In addition to the evidence from systematic reviews, the findings of several controlled observational studies are consistent with existing evidence and suggest improved outcomes with ivermectin treatment.^55,57,59 Similarly, with respect to ivermectin prophylaxis of frontline workers and those at risk, controlled observational studies from Bangladesh and Argentina (the latter which involved 1195 health care workers) have shown apparent reductions in COVID-19 transmission with ivermectin prophylaxis, including in some reports total protection (zero infections) where infection rates in the control group exceeded 50%.^122,123 A very large trial of ivermectin prophylaxis in health care workers in India¹²⁴ covered 3532 participants and reported risk ratios not significantly different from this meta-analysis (prophylaxis outcome).

Clarifying ivermectin safety in pregnancy is a key question in patient acceptability for pregnant women contracting COVID-19. A recent meta-analysis⁵ found little evidence of increased risk of abnormal pregnancies but similarly weak evidence of absence of risk. For (pre-exposure) prophylaxis in pregnancy, where vaccines may be contraindicated, the alternative of hydroxychloroquine has been advocated.^125,126 In addition to safety and relative efficacy, different risk–benefit judgments may be presented for prophylaxis (pre- and post-exposure), and for treatment, with pregnancy a high-risk status for COVID-19.

RCTs in this review did not specifically examine use of ivermectin in the elderly, although this is a known high-risk group for severe COVID-19. In the setting of care homes, it is also notorious for rapid contagion. A standard indication for ivermectin in the elderly is scabies. We identified 2 recent reports suggesting that ivermectin may be efficacious as prevention and treatment of COVID-19 in this age group.^50,127 A letter on positive experience in 7 elder care facilities in Virginia covering 309 patients was sent to NIH¹²⁷ and has recently been submitted for publication.

There is also evidence emerging from countries where ivermectin has been implemented. For example, Peru had a very high death toll from COVID-19 early on in the pandemic.¹²⁸ Based on observational evidence, the Peruvian government approved ivermectin for use against COVID-19 in May 2020.¹²⁸ After implementation, death rates in 8 states were reduced between 64% and 91% over a two-month period.¹²⁸ Another analysis of Peruvian data from 24 states with early ivermectin deployment has reported a drop in excess deaths of 59% at 30+ days and of 75% at 45+ days.¹²⁹ However, factors such as change in behavior, social distancing, and face-mask use could have played a role in this reduction.

Other considerations related to the use of ivermectin treatment in the COVID-19 pandemic include people’s values and preferences, equity implications, acceptability, and feasibility.¹³⁰ None of the identified reviews specifically discussed these criteria in relation to ivermectin. However, in health care decision making, evidence on effectiveness is seldom taken in isolation without considering these factors. Ultimately, if ivermectin is to be more widespread in its implementation, then some considerations are needed related to these decision-making criteria specified in the GRADE-DECIDE framework.¹³⁰

There are numerous emerging ongoing clinical trials assessing ivermectin for COVID-19. The trade-off with policy and potential implementation based on evidence synthesis reviews and/or RCTs will vary considerably from country to country. Certain South American countries, Indian states, and, more recently, Slovakia and other countries in Europe have implemented its use for COVID-19.^{129,131,132,133,134} A recent survey of global trends¹¹⁸ documents usage worldwide. Despite ivermectin being a low-cost medication in many countries globally, the apparent shortage of economic evaluations indicates that economic evidence on ivermectin for treatment and prophylaxis of SARS-CoV-2 is currently lacking. This may impact more on LMICs that are potentially waiting for guidance from organizations like the WHO.

Given the evidence of efficacy, safety, low cost, and current death rates, ivermectin is likely to have an impact on health and economic outcomes of the pandemic across many countries. Ivermectin is not a new and experimental drug with an unknown safety profile. It is a WHO “Essential Medicine” already used in several different indications, in colossal cumulative volumes. Corticosteroids have become an accepted standard of care in COVID-19, based on a single RCT of dexamethasone.¹ If a single RCT is sufficient for the adoption of dexamethasone, then a fortiori the evidence of 2 dozen RCTs supports the adoption of ivermectin.

Ivermectin is likely to be an equitable, acceptable, and feasible global intervention against COVID-19. Health professionals should strongly consider its use, in both treatment and prophylaxis.

ACKNOWLEDGMENTS

Footnotes

REFERENCES