There’s little evidence that ivermectin can treat or prevent coronavirus, experts say

By Patricia B. Mirasol

THERE IS “low quality of evidence” that ivermectin can be used to prevent or treat coronavirus disease 2019 (COVID-19), according to recommendations from the University of the Philippines Manila’s Institute of Clinical Epidemiology, the Philippine Society for Microbiology and Infectious Diseases (PSMID), and the Department of Science and Technology’s Philippine Council for Health Research and Development.

There is no compelling evidence either that melatonin, vitamins C and D, and zinc will work in preventing or treating COVID-19, according to the Philippine COVID-19 Living Recommendations discussed in a March 30 forum organized by the Philippine College of Physicians and PSMID.

Here are excerpts from the forum.

Q: What is ivermectin?

A: It is an anti-parasitic drug approved by the Food and Drug Administration (FDA) for the treatment of malaria, head lice, and scabies.

Q. Is ivermectin an effective chemoprophylaxis (the prevention of infectious disease by the use of chemical agents) for COVID-19?

A. At present, randomized controlled trials (RCTs) — considered to be the gold standard for determining causal associations in clinical research — do not show that ivermectin has any COVID-19 mortality benefit. Neither do they show any significant reduction in the duration of hospitalization. The current recommendations will be updated as more evidence is generated from the ongoing trials.

“There are observational studies that show potential benefits, but we don’t have the amount of data that is enough [for the drug] to be found effective. When it comes to using ivermectin as chemoprophylaxis for COVID-19, it’s best to wait for the results of the RCTs,” said Dr. Joseph Adrian L. Buensalido, an expert in infectious diseases.

Added Dr. Cecilia Nelia C. Maramba-Lazarte, a clinical trial and research methods expert: “High doses may be needed to achieve a serum level which is antiviral against COVID-19 … the safety of these doses have not been well studied.”

Q: Why did the FDA open the application for a compassionate special permit for ivermectin?

A: “This is the correct process so that evidence can be reviewed,” said Dr. Buensalido. “This doesn’t mean acceptance for ivermectin by the FDA. It means the FDA is willing to listen, look at the data, and rule for or against it.”

Q: What are your thoughts on sellers who say they are not selling “therapeutic grade” but “food grade” doses of ivermectin?

A: “It’s not food so how can it be food grade?,” asked Dr. Lazarte. “Maybe it’s veterinary grade, which is even worse for humans.”

Q: What is melatonin?

A: It is the natural hormone your body secretes that helps to maintain your wake-sleep cycle (also called “biological clock”).  Supplements are used to treat sleep disorders and also have potent anti-inflammatory capabilities.

“Melatonin is banned as an over-the-counter medication in countries like Japan, Australia, the United Kingdom, and parts of the European Union,” said Dr. Lazarte. “They have found that the medications [in the market] contain doses from less than 83% to up to 473% of what is labeled. Some are also laced with serotonin.”

Q: Can melatonin be given as an adjunct treatment for COVID-19?

A: According to the Philippine COVID-19 Living Recommendations, there is insufficient or low quality of evidence to recommend melatonin as an adjunct treatment (a treatment that is administered in conjunction with a patient’s ongoing therapy) for COVID-19.

“There’s only one RCT on melatonin so far,” said Dr. Buensalido, “and it shows a very low certainty of benefit for mortality, time to recovery, length of stay, or pulmonary involvement.”

Q: What is vitamin C?

A:Ascorbic acid or vitamin C occurs naturally in foods such as citrus fruit, tomatoes, potatoes, and leafy vegetables. It is important for bones and connective tissues, muscles, and blood vessels. Vitamin C also helps the body absorb iron, which is needed for red blood cell production. It is a potent antioxidant and immune booster.

Q: Can vitamin C be used as a treatment for COVID-19?

A: At the moment, there is insufficient or low quality of evidence to recommend vitamin C as an adjunct treatment for COVID-19, according to the Philippine COVID-19 Living Recommendations.

Q: What is vitamin D?

A: It is not actually a vitamin, but a prohormone that it is converted into a hormone by our body. Vitamin D acts on our bones, intestines, kidneys and parathyroid glands to keep calcium in balance throughout our body. Vitamin D receptors are also located within our cardiovascular system, lungs, pancreas, skeletal muscle, skin, and reproductive organs.

Q: Can vitamin D supplements be used as a form of prevention against COVID-19?

A: There is no clinical evidence that vitamin D supplements should be used in the prevention or treatment of COVID-19, according to a May 2020 study by the Asia Pacific Center for Evidenced Based Healthcare. The panel of the Philippine COVID-19 Living Recommendations also recommends against vitamin D as a form of prevention for COVID-19 due to very low quality of evidence.

An RCT published on Feb. 17 describing the effects of a single high dose of vitamin D3 showed that taking such did not significantly reduce hospital length of stay, Dr. Buensalido told the forum audience. “The findings do not support its use for treatment of moderate to severe COVID-19. We await the other trials,” he said.

Q: How about taking vitamin D just before and immediately after vaccination for a better immune response?

A: “If there is vitamin D deficiency, then it is indicated to give vitamin D,” Dr. Buensalido said. “There is no evidence to take it pre-vaccination. It is unlikely to have an effect.”

Q: What is zinc?

A: Zinc is a naturally occurring mineral that is important for growth and for the development and health of body tissues. It also plays a role in the symptom alleviation of viral upper respiratory tract infections (URTI).

“The main cause of the common cold is the rhinovirus. The second most common cause is the coronavirus — although not specifically the one that causes COVID-19,” said Dr. Buensalido. Studies show that a high dose of zinc is much better in shortening the duration of viral URTI.

“More than 75 grams of elemental zinc reduces the duration of viral URTI,” he added.

Q: Can zinc be used to treat COVID-19?

A: According to the aforementioned Philippine COVID-19 Living Recommendations, there is insufficient or very low quality of evidence to recommend zinc as an adjunct treatment for COVID-19.

“Both zinc and vitamin C can be used as a nutritional support, as a lot of patients we see are malnourished,” said Dr. Lazarte. “It can be used as therapy but not necessarily as a treatment for COVID-19.”

Q: Is the absence of harm enough to prescribe all these medicines in selected patients with COVID-19?

A: “These are not harmless,” said Dr. Lazarte. “Even at normal doses, there are some groups of people that will have severe reactions. Open your patients’ eyes to all the possible benefits and harms and weigh everything. It’s a judgment call, but at the moment, it is not recommended.”

WEAR MASKS, WASH HANDS
Apart from safety protocols such as wearing face masks and washing one’s hands, both doctors said that having a healthy lifestyle is the best form of prevention for the general population.

“Get those fruits and vegetables in. It’s just that we like a pill for every ill,” said Dr. Lazarte. “Keeping healthy is doing something. Exercising is doing something.”

Added Dr. Buensalido, “The risks versus benefits ratio should be considered. We need to look at safety and efficacy. Let’s not be too impatient.”