Ivermectin for preventing and treating COVID-19

Is ivermectin effective for COVID-19?

Key messages

We found no evidence to support the use of ivermectin for treating or preventing COVID-19 infection, but the evidence base is limited.

Evaluation of ivermectin is continuing in 31 ongoing studies, and we will update this review with their results when they become available. 

What is ivermectin?

Ivermectin is a medicine used to treat parasites such as intestinal parasites in animals and scabies in humans. It is cheap and is widely used in regions of the world where parasitic infestations are common. It has few unwanted effects. 

Tests in the laboratory show ivermectin can slow the reproduction of the COVID-19 (SARS-CoV-2) virus but such effects would need major doses in humans. Medical regulators have not approved ivermectin for COVID-19. It should only be used as part of well-designed studies (called randomized controlled trials) evaluating potential effects. 

What did we want to find out?

We wanted to know if ivermectin reduces death, illness, and length of infection in people with COVID-19, or is useful in prevention of the disease. We included studies comparing the medicine to placebo (dummy treatment), no treatment, usual care, or treatments for COVID-19 that are known to work to some extent, such as remdesivir or dexamethasone. We excluded studies that compared ivermectin to other drugs that do not work, such as hydroxychloroquine, or that are not known to be effective against COVID-19.

We evaluated the effects of ivermectin in infected people on:

– people dying;
– whether people's COVID-19 symptoms got better or worse; 
– unwanted effects;
– hospital admission or time in hospital; 
– viral clearance.

For prevention, we sought the effect on preventing COVID-19 and SARS-CoV-2 infection.

What did we do? 

We searched for randomized controlled trials that investigated ivermectin to prevent or treat COVID-19 in humans. People being treated with ivermectin had to have laboratory-test confirmed COVID-19 and be receiving treatment in hospital or as outpatients.

We compared and summarized the results of the studies and rated our confidence in the evidence, based on common criteria as to how reliable the evidence is.

What did we find? 

We found 14 studies with 1678 participants that investigated ivermectin compared to no treatment, placebo, or usual care.

For treatment, there were nine studies of people with moderate COVID-19 in hospital and four of outpatients with mild COVID-19. The studies used different doses of ivermectin and different durations of treatment.

One study investigated ivermectin to prevent COVID-19.

We also found 31 ongoing studies, and there are 18 studies still requiring clarification from the authors or not yet published.

Main results 

Treating people in hospital with COVID-19

We don't know whether ivermectin compared with placebo or usual care, 28 days after treatment:

– leads to more or fewer deaths (2 studies, 185 people); 
– worsens or improves patients' condition assessed by need for ventilation (2 studies, 185 people) or oxygen (1 study, 45 people); 
– increases or reduces unwanted events (1 study, 152 people).

Seven days after treatment, we don't know if ivermectin:

– increases or reduces negative COVID-19 tests (2 studies, 159 people).

Ivermectin compared to placebo or usual care may make little or no difference to improving patients' condition 28 days after treatment (1 study, 73 people) or to length of hospital stay (1 study, 45 people).

Treating outpatients with COVID-19

We don't know whether ivermectin compared with placebo or usual care:

– leads to more or fewer deaths 28 days after treatment (2 studies, 422 people); 
– worsens or improves patients' condition 14 days after treatment assessed by need for ventilation (1 study, 398 people); 
– increases or reduces negative COVID-19 tests seven days after treatment (1 study, 24 people).

Ivermectin compared to placebo or usual care may make little or no difference to improving outpatients' condition 14 days after treatment (1 study, 398 people) or to the number of unwanted events 28 days after treatment (2 studies, 422 people).

No studies looked at hospital admissions in outpatients.

Preventing COVID-19

We don't know whether ivermectin leads to more or fewer deaths compared with no drug (1 study, 304 people); no participant died 28 days after the drug. This study reported results for development of COVID-19 symptoms (but not confirmed SARS-CoV-2 infection) and unwanted events, but in a way that we could not include in our analyses. This study did not look at hospital admissions.

What are the limitations of the evidence?

Our confidence in the evidence is very low because we could only include 14 studies with few participants and few events, such as deaths or need for ventilation. The methods differed between studies, and they did not report everything we were interested in, such as quality of life. 

How up to date is this evidence?

The evidence is up to date to 26 May 2021.

Authors' conclusions: 

Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use of ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials.

Read the full abstract...
Background: 

Ivermectin, an antiparasitic agent used to treat parasitic infestations, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the early stages of infection. Currently, evidence on efficacy and safety of ivermectin for prevention of SARS-CoV-2 infection and COVID-19 treatment is conflicting.

Objectives: 

To assess the efficacy and safety of ivermectin compared to no treatment, standard of care, placebo, or any other proven intervention for people with COVID-19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS-CoV-2 (postexposure prophylaxis).

Search strategy: 

We searched the Cochrane COVID-19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), medRxiv, and Research Square, identifying completed and ongoing studies without language restrictions to 26 May 2021.

Selection criteria: 

We included randomized controlled trials (RCTs) comparing ivermectin to no treatment, standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity, treated in inpatient or outpatient settings, and for prevention of SARS-CoV-2 infection.

Co-interventions had to be the same in both study arms. 

We excluded studies comparing ivermectin to other pharmacological interventions with unproven efficacy.

Data collection and analysis: 

We assessed RCTs for bias, using the Cochrane risk of bias 2 tool. The primary analysis excluded studies with high risk of bias. We used GRADE to rate the certainty of evidence for the following outcomes 1. to treat inpatients with moderate-to-severe COVID-19: mortality, clinical worsening or improvement, adverse events, quality of life, duration of hospitalization, and viral clearance; 2. to treat outpatients with mild COVID-19: mortality, clinical worsening or improvement, admission to hospital, adverse events, quality of life, and viral clearance; (3) to prevent SARS-CoV-2 infection: SARS-CoV-2 infection, development of COVID-19 symptoms, adverse events, mortality, admission to hospital, and quality of life.

Main results: 

We found 14 studies with 1678 participants investigating ivermectin compared to no treatment, placebo, or standard of care. No study compared ivermectin to an intervention with proven efficacy. There were nine studies treating participants with moderate COVID-19 in inpatient settings and four treating mild COVID-19 cases in outpatient settings. One study investigated ivermectin for prevention of SARS-CoV-2 infection. Eight studies had an open-label design, six were double-blind and placebo-controlled. Of the 41 study results contributed by included studies, about one third were at overall high risk of bias. 

Ivermectin doses and treatment duration varied among included studies. 

We identified 31 ongoing and 18 studies awaiting classification until publication of results or clarification of inconsistencies.

Ivermectin compared to placebo or standard of care for inpatient COVID-19 treatment

We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.14 to 2.51; 2 studies, 185 participants; very low-certainty evidence) and clinical worsening up to day 28 assessed as need for invasive mechanical ventilation (IMV) (RR 0.55, 95% CI 0.11 to 2.59; 2 studies, 185 participants; very low-certainty evidence) or need for supplemental oxygen (0 participants required supplemental oxygen; 1 study, 45 participants; very low-certainty evidence), adverse events within 28 days (RR 1.21, 95% CI 0.50 to 2.97; 1 study, 152 participants; very low-certainty evidence), and viral clearance at day seven (RR 1.82, 95% CI 0.51 to 6.48; 2 studies, 159 participants; very low-certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on clinical improvement up to 28 days (RR 1.03, 95% CI 0.78 to 1.35; 1 study; 73 participants; low-certainty evidence) and duration of hospitalization (mean difference (MD) −0.10 days, 95% CI −2.43 to 2.23; 1 study; 45 participants; low-certainty evidence). No study reported quality of life up to 28 days.

Ivermectin compared to placebo or standard of care for outpatient COVID-19 treatment

We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality up to 28 days (RR 0.33, 95% CI 0.01 to 8.05; 2 studies, 422 participants; very low-certainty evidence) and clinical worsening up to 14 days assessed as need for IMV (RR 2.97, 95% CI 0.12 to 72.47; 1 study, 398 participants; very low-certainty evidence) or non-IMV or high flow oxygen requirement (0 participants required non-IMV or high flow; 1 study, 398 participants; very low-certainty evidence). We are uncertain whether ivermectin compared to placebo reduces or increases viral clearance at seven days (RR 3.00, 95% CI 0.13 to 67.06; 1 study, 24 participants; low-certainty evidence). Ivermectin may have little or no effect compared to placebo or standard of care on the number of participants with symptoms resolved up to 14 days (RR 1.04, 95% CI 0.89 to 1.21; 1 study, 398 participants; low-certainty evidence) and adverse events within 28 days (RR 0.95, 95% CI 0.86 to 1.05; 2 studies, 422 participants; low-certainty evidence). None of the studies reporting duration of symptoms were eligible for primary analysis. No study reported hospital admission or quality of life up to 14 days.

Ivermectin compared to no treatment for prevention of SARS-CoV-2 infection

We found one study. Mortality up to 28 days was the only outcome eligible for primary analysis. We are uncertain whether ivermectin reduces or increases mortality compared to no treatment (0 participants died; 1 study, 304 participants; very low-certainty evidence). The study reported results for development of COVID-19 symptoms and adverse events up to 14 days that were included in a secondary analysis due to high risk of bias. No study reported SARS-CoV-2 infection, hospital admission, and quality of life up to 14 days.

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