Ivermectin, Hydroxychloroquine and Zinc for COVID-19: What are the Differences?

Ivermectin, hydroxychloroquine and zinc have received various media and social media attention for the past few months. 'No high quality evidence', "can only be used in a clinical trial setting', 'double blinded randomised controlled clinical trial needed', "insufficient data to recommend either for or against the use" are some of the medical and scientific technicalities that you might read in various social media channels. Confused? 

The number of options for the treatment of COVID-19 has increased drastically in recent months, thus making it complicated when it comes to choosing the right combination. In general, there are 3 broad categories of medical interventions:

1. Prevention or Prophylaxis e.g. vaccine
2. Early out-patient treatment
3. Hospital treatment

       

Image credit: Cleveland Clinic

All these treatments come with various technical jargons, thus could be overwhelming and confusing for you as a consumer.

Generally, multiple treatments and strategies are used in combination to achieve the best possible outcome.

In this article, we would like to cover 3 popular treatments i.e. Ivermectin, Hydroxychloroquine and Zinc.

Ivermectin and COVID-19

As of April 2021, there are more than 80 on-going trials globally on Ivermectin for treatment and prevention of COVID-19 on covid-nma.com.

Ivermectin is an anti-parasitic medication widely used in low- and middle-income countries to treat parasitic worm infections 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.

Ivermectin and COVID-19 Updates:

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 Ōmura, 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. 

“When the effectiveness of ivermectin for the COVID-19 pandemic is confirmed with the cooperation of researchers around the world and its clinical use is achieved on a global scale, it could prove to be of great benefit to humanity. It may even 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.”—From Global trends in clinical studies of ivermectin in COVID-19, published in the Japanese Journal of Antibiotics, March, 2021.

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.”

The authors wrote: 

The early stage of viral replication provides a therapeutic window of tremendous opportunity to potentially reduce the risk of more severe sequelae in high risk patients. Precious time is squandered with a ‘wait and see’ approach … resulting in unnecessary hospitalization, morbidity, and death. … In newly diagnosed, high-risk, symptomatic patients with COVID-19, SMDT has a reasonable chance of therapeutic gain with an acceptable benefit-to-risk profile. 

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

Related Ivermectin and COVID-19 Publications:

• Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19 by Kory et al., provisionally accepted on American Journal of Therapeutics.
• Dr. Satoshi Ōmura, 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.

Ivermectin for COVID-19: Real-time meta analysis of 50 studies

• 100% of the 50 studies to date report positive effects (25 statistically significant in isolation). Random effects meta-analysis for early treatment and pooled effects shows an 81% reduction, RR 0.19 [0.09-0.38], and prophylactic use shows 89% improvement, RR 0.11 [0.06-0.22]. Mortality results show 76% lower mortality, RR 0.24 [0.14-0.42] for all treatment delays, and 84% lower, RR 0.16 [0.04-0.63] for early treatment.
• 100% of the 26 Randomized Controlled Trials (RCTs) report positive effects, with an estimated 70% improvement, RR 0.30 [0.20-0.46].
• The probability that an ineffective treatment generated results as positive as the 50 studies to date is estimated to be 1 in 1 quadrillion (p = 0.000000000000001).

Source: ivmmeta.com (constantly updated)

Related: List of Doctors that will prescribe Ivermectin

Hydroxychloroquine and COVID-19

We have combined hydroxychloroquine and chloroquine under 1 category. Hydroxychloroquine, a less toxic derivative of Chloroquine is a widely used medication by people with lupus or arthritis. It was first approved in the 1950s. Chloroquine is used to treat and prevent malaria and amebiasis.

According to a real time meta-analysis of 233 hydroxychloroquine studies:

• HCQ is effective for COVID-19. The probability that an ineffective treatment generated results as positive as the 231 studies to date is estimated to be 1 in 3 quadrillion (p = 0.0000000000000003).           
• Early treatment is most successful, with 100% of 28 studies reporting a positive effect (12 statistically significant in isolation) and an estimated reduction of 64% in the effect measured (death, hospitalization, etc.) using a random effects meta-analysis, RR 0.36 [0.25-0.51].
• 92% of Randomized Controlled Trials (RCTs) for early, PrEP, or PEP treatment report positive effects, the probability of this happening for an ineffective treatment is 0.0032.
• There is evidence of bias towards publishing negative results. 88% of prospective studies report positive effects, and only 73% of retrospective studies do.
• Studies from North America are 3.9 times more likely to report negative results than studies from the rest of the world combined, p = 0.0000000013.

Source: hcqmeta.com (constantly updated)

Hydroxychloroquine and COVID-19 Updates:

Jan 24, 2021: Dr Vladimir Zelenko published a white paper on "Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing".

With the latest large Iranian study, we now have 13 studies on early hydroxychloroquine treatment with mortality data. 

With unambiguous results. pic.twitter.com/FvYW7Y1egX

— Covid19Crusher (@Covid19Crusher) April 7, 2021

Zinc and COVID-19

Foods that are high in zinc include oysters, crab, lobster, mussels, red meat, and poultry. Cereals are often fortified with zinc. Most multivitamin and nutritional supplements contain zinc.

As of April 2021, there are more than 50 studies that have been launched to investigate the benefits of Zinc against COVID-19. You can review the status of these trials on clinicaltrials.gov.

A retrospective observational study (Carlucci P, Sep 2020) compared zinc supplementation to no zinc supplementation in hospitalized patients with COVID-19 who received hydroxychloroquine and azithromycin from March 2 to April 5, 2020. A total of 932 patients were included in this analysis; 411 patients received zinc, and 521 did not. After adjusting for the time at which zinc sulphate was added to the protocol, an increased frequency of being discharged home and reduction in mortality or transfer to hospice among patients who did not require ICU level of care remained significant. This study provides the first in vivo evidence that zinc sulphate may play a role in therapeutic management for COVID-19.

A study in Spain (Gonzalez, The Lancet preprint, Oct 2020) among people hospitalised with COVID-19 found that having very low blood levels of zinc was associated with more severe disease and higher mortality rates.

Taking zinc long term is typically safe for healthy adults, as long as the daily dose is under the set upper limit of 40 mg of elemental zinc (PubMed).

Be aware that typical daily doses of zinc provided by zinc lozenges generally exceed tolerable upper limits for zinc, and for this reason, they should not be used for longer than about a week. 

Excessive doses may interfere with copper absorption, which could negatively affect your immune system as it can cause copper deficiencies, blood disorders, impair the absorption of antibiotics and potentially permanent nerve damage or loss of smell.

The ideal dose for prevention while the COVID-19 risk is high is 40-100 mg/d, a portion of which comes from zinc lozenges to spread the zinc through the tissues of the nose, mouth and throat. It should be accompanied by at least 1 mg copper from food and supplements for every 15 mg zinc.

Do take note that you should keep the dosage back to within 40 mg/d once the exposure risk is back to normal.

Zinc Sulphate is also part of Dr. Vladimir Zelenko anti-coronavirus experimental protocol. Please take note that the protocol is experimental and has not been 100% proven. Do discuss with your doctor before taking the medication as per the protocol. You can check out his publication in the International Journal of Antimicrobial Agents. 

Based on the statement released on 2 October by the U.S. president’s physician, zinc is also part of the treatment given to the US President. According to the president's physician, "Trump has been taking zinc, vitamin D, famotidine, melatonin and a daily aspirin.”

Editor's note: Hydroxychloroquine is a zinc ionophore. If increased intracellular Zn ion concentration is required to disrupt viral replication, perhaps using multiple zinc ionophores would increase that concentration thus decreasing viral replication further. Other OTC (over the counter) zinc ionophores include quercetin (QCT) and epigallocatechin-gallate (EGCG – green tea extract).

Related: Best Zinc Supplement 2021

Ivermectin vs Hydroxychloroquine vs Zinc

Clinical evidence to date has reported promising results (see above) for Ivermectin in prevention, early treatment as well as late treatment for COVID-19. While both Ivermectin and Hydroxychloroquine might be useful for early treatment, Ivermectin has a broader potential benefit i.e. prevention, early treatment as well as late treatment / hospital treatment.

Hydroxychloroquine and Quercetin are both zinc ionophores i.e. they transport zinc into the cells. A study (Frontera, Oct 2020) published in the NIH Preprint database, showed that zinc with hydroxychloroquine was associated with increased rates of discharge home and a 24% reduced risk of in-hospital death rate among COVID-19 patients, while neither zinc alone nor hydroxychloroquine alone reduced death rate.

Although ivermectin and hydroxychloroquine are relatively safe drugs, they are still synthetic chemicals that can have side effects. Quercetin and Vitamin D, C and 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.

Key Takeaways

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.

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.

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Supplements you can purchase from Amazon for COVID-19 'prevention' based on the FLCCC prevention protocol >

• Quercetin: 1 capsule daily (Amazon)

• Zinc, Vitamin D3 and Vitamin C: 1 lozenge daily (Amazon)

• Melatonin: 1 tablet before bedtime (causes drowsiness) (Amazon)

Related item: Fingertip Pulse Oximeter (Amazon)

Be aware that most supplements have two categories of dosages: i.e. 

1. treatment (therapeutic) dosages are normally higher than the RDA dosages and 
2. 'maintenance' or 'preventive' dosages that are normally based on the recommended daily value.

You should ideally supplement your micro-nutrients from healthy and wholesome foods, fruits and vegetables.

Disclaimer: Always see your doctor before taking these supplements. Be aware that most of the 'treatment' dosages are above the recommended dietary allowance (RDA) and therefore such dosages should not be maintained on a long term basis.