Does Ivermectin Work against COVID-19?

Some doctors and media channels argue that there is very little evidence to support the use of ivermectin to treat COVID-19 ('CO' stands for corona, 'VI' for virus, and 'D' for disease). However, you can find a summary of the 57 studies on ivermectin done by 509 authors from c19ivermectin.com (constantly updated).

Let's dive into some facts and details.

What is Ivermectin?

Ivermectin is an anti-parasitic medication widely used in low and middle-income countries to treat parasitic worm infections, lice and mites in adults and children. It’s been used for decades for this purpose by over 3.7 billion people, and is considered safe and effective. It has an increasing list of indications due to its antiviral and anti-inflammatory properties, and is included on the WHO’s Model List of Essential Medicines.

Recently ivermectin has also been studied to treat a range of viruses.

How is Ivermectin thought to work on COVID-19?

  • For the SARS-CoV-2 virus to make you sick, it has to first infect your cells.
  • Then while inside the cell, the virus makes heaps of copies of itself, so it can spread around your body.
  • The virus also has ways of reducing the way your body fights the infection.
  • During the infection of the cell, some viral proteins go into the cell nucleus, and from here they can decrease the body’s ability to fight the virus, which means the infection can get worse.
  • To get into the nucleus the viral proteins need to bind a cargo transporter which lets them in.
  • Ivermectin can block the cargo transporter, so the viral proteins can’t get into the nucleus. This is how the scientists believe Ivermectin works against SARS-CoV-2 virus.
  • By taking Ivermectin, it means the body can fight the infection like normal, because its antiviral response hasn’t been reduced by the viral proteins.

Is Ivermectin an approved medicine by the US FDA?

  • Ivermectin tablets (Stromectol) are an approved by the FDA for use in intestinal worms Strongyloides stercoralis and Onchocerca volvulus.
  • Ivermectin cream 1% (Soolantra) is FDA approved for rosacea.
  • Ivermectin tablets are also used off-label for a number of other conditions.
  • Ivermectin intended for animal use should not be taken by humans.
As Ivermectin is already a FDA approved medicine we already know that it has been established as safe for human use when used at the standard dose.

Both oral and topical ivermectin have a good safety profile at standard dosing levels (drugs.com).

Ivermectin and Clinical Studies

As of June 2021, there are more than 80 on-going trials globally on Ivermectin for treatment and prevention of COVID-19 on covid-nma.com.
           
Source: covid-nma.com
  • Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 by Kory et al., published on American Journal of Therapeutics.
  • Dr. Satoshi ┼îmura, co-author of the newly published paper, “Global trends in clinical studies of ivermectin in COVID-19” was one of the four researchers from Kitasato University in Tokyo, Japan who received the Nobel Prize in Physiology or Medicine in 2015 for their discovery of ivermectin. Global trends in clinical studies of ivermectin in COVID-19, published in the Japanese Journal of Antibiotics, March, 2021.
  • A multi-centre randomised controlled study in Egypt (Elgazzar, Research Square) reported that the death rate was significantly lower in Ivermectin treated patients group (severe patients) vs non-Ivermectin group (2% vs 20%). 1,300 patients were included in this randomized controlled trial. 
  • This randomized controlled trial out of Iran (Hashim, pre-print) used Ivermectin and Doxycycline in mild, moderate, and severe hospitalized COVID-19 patients. No patients in the mild and moderate COVID-19 category died and 18% of the severe patients perished taking this medication combo. In the control group, no mild-moderate patients died, but 27% of the severe COVID patients died. The patients who also got Ivermectin had a shorter recovery.
  • A randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical trial at five hospitals (Iran) and 180 patients with mild to severe disease (Niaee, ResearchSquare, Nov 2020). Ivermectin as an adjunct reduced the rate of mortality, the duration of low oxygen saturation, and the duration of hospitalization.
  • The ICON study in US, published in Chest, Oct 2020 reported that Ivermectin treatment was associated with lower death rate vs Control (13.3% vs 24.5%) during treatment of COVID-19, especially in patients with severe pulmonary involvement.
  • A double-blinded randomised controlled study in Bangladesh (Mahmud et al) reported that the death rate was 0% (0/183) in the Ivermectin arm vs 1.67% (3/180) in the control arm in mild to moderate COVID-19 patients.
  • The IDEA (Ivermectin, Dexamethasone, Enoxaparin and Aspirin) study from Argentina reported 1 death out of 167 patients studied. The patient that died was a severe COVID-19 patient that required ventilator support.
  • The pre-AndroCoV trial from Brazil reported that early detection of COVID-19 followed by a pharmaceutical approach with different drug combinations (Azithromycin, Hydroxychloroquine, Nitazonide, Ivermectin) yielded irrefutable differences compared to non-treated controls in terms of clinical outcomes, ethically disallowing placebo-control randomized clinical trials in the early stage of COVID-19 due to the marked improvements.
  • A retrospective study out of Bangladesh (Khan, Archivos de Bronconeumologia 2020). This retrospective study enrolled a total of 325 from April to June 2020. 248 adult COVID-19 patients were looked at in two groups, 115 received ivermectin plus standard care (SC), while 133 received only standard care (SC). This study showed that Ivermectin was efficient at rapidly clearing SARS-CoV-2 from nasal swabs (median 4 days). This was much shorter than in the COVID-19 patients receiving only SC (15 days) or receiving a combination of three antiviral drugs (7–12 days). In addition, fewer Ivermectin patients developed respiratory distress leading to ICU admission. In fact, with Ivermectin, there was a quick hospital discharge (median 9 days) in 114 out of 115 patients; the one remaining patient had been admitted with advanced disease.
For more details of more than 50 studies done by more than 500 authors, check out c19ivermectin.com (constantly updated).

Precautionary Note: Ivermectin has a number of potentially serious drug-drug interactions. Please check for potential drug interaction at Ivermectin Drug Interactions (Drugs.com). The most important drug interactions occur with cyclosporin, tacrolimus, anti-retroviral drugs, and certain anti-fungal drugs. 

Due to the possible drug interaction between quercetin and ivermectin (may increase ivermectin levels), these drugs should not be taken simultaneously (i.e. should be staggered morning and night). 

Ivermectin is also lipophilic and therefore, bioavailability is maximised on a full stomach; or best to be taken with meal.

FLCCC Protocols

For prevention, the Front Line COVID-19 Critical Care Working Group (FLCCC) recommends (updated April 26, 2021):
  • Vitamin D3: 1000–3000 IU/day. Note RDA (Recommended Daily Allowance) is 800–1000 IU/day. The safe upper-dose daily limit is likely < 4000 IU/day. Vitamin D deficiency has been associated with an increased risk of acquiring COVID-19 and from dying from the disease. Vitamin D supplementation may therefore prove to be an effective and cheap intervention to lessen the impact of this disease, particularly in vulnerable populations, i.e. the elderly and obese. (Amazon)
  • Vitamin C: 500 - 1,000 mg BID (twice daily) (Amazon)
  • Quercetin: 250 mg daily. It is likely that vitamin C and quercetin have synergistic prophylactic benefit. Quercetin should be used with caution in patients with hypothyroidism and TSH levels should be monitored. (Amazon)
  • Melatonin: 6 mg before bedtime (causes drowsiness). (Amazon)
  • Zinc: 30 - 40 mg/day (elemental zinc). Zinc lozenges are preferred. (Amazon)
  • Ivermectin for 
    • prevention in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc): 0.2 mg/kg per dose (take with or after meals) — one dose today, repeat after 48 hours, then one dose weekly. (also see ClinTrials.gov NCT04425850). 
    • Post COVID-19 exposure prevention: 0.2 mg/kg per dose (take with or after meals)  — one dose today, repeat after 48 hours.
For early outpatient protocol (COVID-19 positive), the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated Apr 26, 2021):
  • Vitamin D3 — 4000 IU/day. (Amazon)
  • Vitamin C: 500 - 1,000 mg BID (twice daily) (Amazon)
  • Quercetin: 250 mg twice a day. (Amazon)
  • Melatonin: 10 mg before bedtime (causes drowsiness). (Amazon)
  • Zinc: 100 mg/day. Zinc lozenges are preferred. (Amazon)
  • Ivermectin: 0.2–0.4 mg/kg per dose (take with or after meals) — one dose daily, take for 5 days or until recovered. (Find a Doctor)
  • Fluvoxamine: 50 mg twice daily for 10–14 days. Add to ivermectin if: 1) minimal response after 2 days of ivermectin; 2) in regions with more aggressive variants; 3) treatment started on or after day 5 of symptoms or in pulmonary phase; or 4) numerous co-morbidities/risk factors. Avoid if patient is already on an SSRI (selective serotonin reuptake inhibitor).
  • Nasopharyngeal Sanitation: Steamed essential oil inhalation 3 times a day (i.e. vapo-rub) and/or chlorhexidine/benzydamine mouthwash gargles and Betadine nasal spray 2–3 times a day.
  • Aspirin: 325 m/day unless contraindicated.
  • Pulse Oximeter: FLCCC also recommend monitoring your oxygen saturation with a pulse oximeter and to go to the hospital if you get below 94%.
The medical evidence to support each drug and nutrient can be found under “Medical Evidence” on the FLCCC’s website.


Note on Zinc supplements: How much zinc you should take per day depends on the type and forms of zinc, as each supplement contains a different amount of 'elemental zinc'. The percentage of elemental zinc varies by form. 

For example, approximately 23% of zinc sulfate consists of elemental zinc; thus, 220 mg of zinc sulfate contains 50 mg of elemental zinc (NIH). Zinc picolinate (20% of elemental zinc), zinc ascorbate (15%), zinc chloride (48%), zinc carbonate (52%), zinc citrate (31%), zinc bisglycinate (25%) (Ref) and zinc gluconate (14%) and zinc oxide (80%) (Ref).

The AAPS (Association of American Physicians and Surgeons) recommends zinc sulfate, gluconate or citrate. These forms are available in pharmacies, health food stores, and sold online. Zinc sulfate 220 mg provides 50 mg elemental zinc, the recommended anti-viral dose. Zinc in the form of zinc picolinate form is not recommended following reports of liver damage and tumors from studies about 20 years ago. Following these reports, the German Commission E that regulates supplements used in medical practice in Germany banned this form of zinc.

Precaution: Quercetin has one moderate drug interaction with warfarin. Do not take quercetin without medical advice if you are using warfarin.

Ivermectin and COVID-19 Updates

Results of Ivermectin's success in treating COVID-19 outbreaks in India, Mexico, Peru, Paraquay, Argentina, Brazil and Slovakia.

May 16, 2021: Do the NIH and WHO COVID treatment recommendations need to be fixed? By Steve Kirsch. Published on TrialSiteNews.
Great article on where we stand on the COVID-19 treatment front debate - COVID19Crusher

May 03, 2021 - Joint Statement on Widespread Use of Ivermectin in India for Prevention and Early Treatment by U.K. Evidence-Based Medicine Consultancy Ltd (E-BMC Ltd) and U.S. FLCCC (Front Line Critical Care Alliance).

Apr 14, 2021: Open Letter by U.S. Doctors: JAMA Ivermectin Study (Lopez-Medina et al) Is Fatally Flawed, TrialSiteNews reported.

Apr 9, 2021: FLCCC (Front Line Critical Care Alliance) statement on Washington Post article.

Apr 1, 2021: WHO reaches ivermectin recommendation without a vote, TrialSiteNews reported.

Mar 31, 2021: FLCCC (Front Line Critical Care Alliance) statement on WHO's Ivermectin guide.

Mar 30, 2021: Argentina Ministry of Health Clinical Trial: Ivermectin Shows Benefit Treating Outpatients with Mild COVID-19; TrialSiteNews reported.

Mar 10, 2021: Dr. Satoshi ┼îmura, co-author of the newly published paper, “Global trends in clinical studies of ivermectin in COVID-19” was one of the four researchers from Kitasato University in Tokyo,           Japan who received the Nobel Prize in Physiology or Medicine in 2015 for their discovery of ivermectin. 

Mar 5, 2021: [Europe] Ivermectin is now approved for COVID-19 use in 2 European countries: Czech Republic and Slovakia.

Feb 25, 2021: Drug used to treat lice and scabies drug could cut Covid deaths by up to 75%, research suggests, DailyMail reported (more than 16,000 shares).

Feb 25, 2021: Scabies and head lice drug could be 'global solution to the pandemic' says study; Mirror UK reported.

Jan 19, 2021: A pilot study published in the Lancet on January 19, 2021 showed some promising results but the authors concluded that the study warrants further exploration under larger trials with clinical outcomes in patients with risk factors or more severe disease.

Jan 18, 2021: Updated version of Frequently Asked Questions on Ivermectin in COVID-19 by the FLCCC.

Jan 16, 2021: Apparently, a judge just ordered the Millard Fillmore Suburban Hospital to allow an 80-year old woman to be treated with Ivermectin. According to the family and attorney, the treatment saved the life of Judith Smentkiewicz. Apparently, a doctor ordered the drug off-label in the intensive care unit (ICU), and as she improved, more than likely due to the drug, she was moved to another unit, and the doctor there stepped in and disallowed the use of the drug. Family members immediately involved lawyers and legal action to resume treatment. The New York Supreme Court Judge Henry J. Nowak aligned with the family; TrialSiteNews reported.

Jan 14, 2021: The National Institutes (NIH) has issued a new statement on the use of the anti-parasitic drug ivermectin for the treatment of COVID-19. Previously, it recommended against this treatment, but now states that its Panel “has determined that there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19.”

Jan 13, 2021: The BIRD meeting was convened by Dr. Tess Lawrie in order to present the findings from her rapid systematic review and meta-analysis of studies on the use of ivermectin to prevent and treat COVID-19. Dr. Lawrie presented evidence in the form of a DECIDE evidence-to-decision framework, a format used by the World Health Organization for the development of guidelines and recommendations in medical practice. Twenty experts from around the world and the UK attended the meeting, including 13 clinicians, and seven representatives from the public.

Dec 30, 2020: An essential updated review of COVID-19 early-treatment best practices was published. (abstract | PDF | HTML)

This international collaboration — comprised of physicians, like lead author Peter McCullough, MD, courageously treating patients despite the prevalence of “therapeutic nihilism” among government agencies like the NIH and FDA — outlines the urgency of, “prompt early initiation of sequenced multidrug therapy (SMDT) … to stem the tide of hospitalizations and death.”

Included in the paper is a “sequential multidrug treatment algorithm” and summaries of the rationale and evidence for each component.

Other Potential Treatments

Clinical evidence to date has reported promising results (see above) for Ivermectin in prevention, early treatment as well as late treatment for COVID-19. 

If you simply cannot get ivermectin, quercetin is a viable stand-in. Quercetin works best when taken with vitamin C, Bromelain and Zinc. Vitamin C helps activate it and bromelain helps with the absorption. 

Although ivermectin is a relatively safe medication, it's still a synthetic chemical that might have side effects. Quercetin and Vitamin D, C, Zinc are nutrients that your body require for optimal health. Nutrients are safer alternatives especially if your risk is low e.g. age below 50 and no other chronic illness. Discuss with your doctor on the benefit vs risk for each treatment. If you are on multiple medications, be aware of supplement-drug interactions that might enhance the possibilities of adverse effects.

A summary table analysing more than 600 studies for COVID-19 treatments is provided below (credit: c19early.com):

   

Summary

The important key takeaway is that you should never attempt to self medicate without the guidance of a licensed medical provider. If you are not a medical doctor, you are likely to find the above information overwhelming. The aim of this article is to empower you with a better understanding of the options available and to discuss the options with your medical doctor.

Most drugs including supplements are not 100% safe. It's about weighing the potential benefits vs the potential risks. As the topic is complicated, it's best you discuss with your medical doctor on what is best for you as everyone is unique.

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