Ivermectin: why a potential COVID treatment isn’t recommended for use - The Conversation UK

Posted: 19 Apr 2021 07:12 AM PDT

As the search continues for treatments for COVID-19, the results from a number of studies have led to changes in the advice on which drugs to give people who are suffering from the disease.

The European Medicines Agency and the United States National Institutes of Health have recently stated that one previously promising treatment – the antiparasitic drug, ivermectin – is not recommended for use in routine management of COVID-19 patients.

Despite these decisions, support for ivermectin has been circulating on social media and in WhatsApp groups, with rumours abounding that the drug is being blocked on purpose. Some have dubbed it the "new hydroxycholoroquine", after a treatment that received a significant amount of online support but was found in trials to be ineffective against COVID-19.

So what is ivermectin, and why have national agencies ruled against it?

What is ivermectin?

Ivermectin was first developed in the 1970s from a bacterium in a soil sample collected from woods alongside a Japanese golf course (no other source has ever been found).

In the intervening years, the effectiveness of ivermectin and its derivatives in treating parasitic worm infections transformed human and veterinary medicine, leading to a Nobel Prize for its discoverers, William C Campbell and Satoshi Ömura.

In humans, ivermectin is currently prescribed in tablet form to treat certain roundworm infections that cause illnesses such as river blindness. It may also be applied as a cream to control the common inflammatory skin condition papulopustular rosacea.

A packet of ivrmectin capsules. — The drug has its supporters, but not enough evidence for use against COVID. HJBC/Shutterstock

But ivermectin is most commonly used for veterinary parasitic diseases, especially gastrointestinal worm infestations. Consequently, it is readily available and relatively inexpensive.

As ivermectin is more extensively used in veterinary than human medicine, however, the US Food and Drug Administration found it necessary to issue a warning in April 2020 against use of veterinary preparations in human patients with COVID-19.

Why might it be used to treat COVID?

How did a drug mainly used to treat intestinal parasites in cows come to be of interest to doctors treating humans with COVID-19?

In early 2020, a paper was made public (before it was reviewed by other scientists) which showed ivermectin suppresses the replication of the SARS-CoV-2 virus, which causes COVID-19, under laboratory conditions. This was one of many studies over the past 50 years to show that the antiparisitic drug could also have antiviral uses.

There appear to be two key ways in which the drug could prevent coronavirus replication. First, it could prevent the virus from suppressing our cells' natural antiviral responses. Second, it's possible the drug prevents the "spike" protein on the surface of the virus from binding to the receptors that allow it to enter our cells. Along with the anti-inflammatory actions apparent from ivermectin's efficacy in rosacea, these may point towards useful effects in a viral disease that causes significant inflammation.

These initial findings were used as the basis of numerous recommendations for ivermectin's use to treat COVID-19, particularly in Latin America, which were later retracted.

Why is it controversial?

Since then, there have been numerous studies into ivermectin as a potential treatment for COVID-19.

In late 2020, a research group in India was able to summarise the results of four small studies of ivermectin as an add-on treatment in COVID-19 patients. This review showed a statistically significant improvement in survival among patients who received ivermectin in addition to other treatments.

But the authors stated clearly that the quality of the evidence was low and that the findings should be treated with caution. As is frequently the case for reviews of multiple small studies, the paper suggested that further trials were needed to determine whether ivermectin was indeed clinically effective.

A shaggy cow in a field — Ivermectin: we know it's good for cows, but is it good for COVID? Farlap/Alamy Stock Photo

A controversy subsequently blew up over an article by the Front Line COVID-19 Critical Care Alliance, a group of doctors and researchers that lobbies for the use of ivermectin.

This article, summarising multiple small studies of the effects of ivermectin on COVID-19 patients, was provisionally accepted for publication in the journal Frontiers in Pharmacology in January 2021 but then rejected and removed from the journal's website in March. The journal's editor stated that the standard of evidence in the paper was insufficient and that the authors were inappropriately promoting their own ivermectin-based treatment.

One larger randomised clinical trial was published in March 2021. This showed no effect of ivermectin on duration of symptoms of adults with mild COVID-19. The authors stated that the findings did not support the use of ivermectin in these patients, but again highlighted that larger trials were needed to determine whether the drug had other benefits.

Why isn't it recommended?

While some other studies did appear to show benefits of ivermectin, many did not. These were summarised by the National Institutes of Health, showing severe limitations arising from small sample sizes and problems with study design.

Both the National Institutes of Health and the European Medicines Agency judged, on the basis of these studies, that there is currently insufficient evidence to support the use of ivermectin in treatment of COVID-19.

More studies are underway. A large, multicentre trial began in February to determine the effectiveness of ivermectin as well as metformin (an anti-diabetes medication) and fluvoxamine (an antidepressant) in preventing COVID-19 disease progression.

It would therefore be premature to conclude absolutely that ivermectin has no place in COVID-19 treatment. On the basis of current evidence, however, its use cannot be recommended.

Idaho Doctor Makes Baseless Claims About Safety of COVID-19 Vaccines - FactCheck.org

Posted: 19 Apr 2021 03:21 PM PDT

SciCheck Digest

A viral video features a doctor making dubious claims about COVID-19 vaccines and treatments at a forum hosted by Idaho's lieutenant governor. Dr. Ryan Cole claims mRNA vaccines cause cancer and autoimmune diseases, but the lead author of the paper on which Cole based that claim told us there is no evidence mRNA vaccines cause those ailments.

Full Story

More than 565,000 people have died from COVID-19 in the U.S., but two, effective mRNA vaccines are now available. Some treatments for certain patients, such as those hospitalized or receiving oxygen, have also been approved or authorized by federal agencies, and they continue to be studied.

Since the pandemic began, however, politicized social media posts have featured doctors, some looking authoritative in white coats, while spreading dubious claims about both vaccines and treatments for COVID-19. The most recent example in this misinformation niche is Dr. Ryan Cole, who owns a medical lab in Idaho.

Cole is featured in a video that has amassed more than a million views. He makes a variety of claims, some of which we've addressed before.

The video was recorded while he spoke at a forum on March 4 hosted by Idaho's lieutenant governor, Janice McGeachin, a Republican, and it was posted by a Libertarian organization called the Idaho Freedom Foundation.

McGeachin was featured in an October post by that group, posing with a Bible and a gun in a video that advocated against public health measures related to the pandemic and asked viewers to sign a statement saying that "any order issued in the future will be ignored."

Cole said in an interview with FactCheck.org that he's "not affiliated with any political party, group or organization." According to the Idaho Secretary of State's office, Cole is registered as a Republican.

In the March 4 video, Cole makes claims suggesting that federal agencies have acted nefariously, as well as claims that undermine vaccines and promise miracle treatments.

We'll address his four main claims.

Although there is no evidence to support this, Cole suggested that some of the COVID-19 vaccines could cause cancer or autoimmune diseases.
Again, without evidence, Cole suggested that the federal government withheld a treatment for COVID-19 in order to "vend" a vaccine.
Studies haven't proved that ivermectin is effective in treating COVID-19, but Cole claimed that federal agencies "have suppressed this life-saving medication."
Cole said public health officials should encourage people to take vitamin D supplements rather than wear masks or stay physically distant from others.

Vaccine Safety

Two of the COVID-19 vaccines available in the U.S. use messenger RNA, or mRNA, to train recipients' immune systems to make antibodies that fight the virus that causes COVID-19. (See SciCheck's articles on those vaccines: "A Guide to Moderna's COVID-19 Vaccine" and "A Guide to Pfizer/BioNTech's COVID-19 Vaccine.")

These are the first vaccines using mRNA technology authorized in the U.S., but scientists have been developing and testing mRNA vaccines for years, including in people during clinical trials. Still, misinformation exploiting fears of this new technology has been common online.

To those bogus claims, Cole has now added: "mRNA trials in mammals have led to odd cancers. mRNA trials on mammals have led to autoimmune diseases — not right away, six, nine, 12 months later."

We asked Cole to provide support for those claims, and he referred us to a 2018 paper published in the journal Nature Reviews Drug Discovery that reviewed trials and studies of various, earlier mRNA vaccines.

But that paper doesn't support his statement.

Norbert Pardi, a research assistant professor of medicine at the University of Pennsylvania, was the lead author of the paper. He told us in an email, "No publications demonstrate that mRNA vaccines cause cancer or autoimmune diseases."

Pardi's 19-page paper does make one passing reference to autoimmune diseases, which is what Cole highlighted to us.

The paper says: "A possible concern could be that some mRNA-based vaccine platforms induce potent type I interferon responses, which have been associated not only with inflammation but also potentially with autoimmunity. Thus, identification of individuals at an increased risk of autoimmune reactions before mRNA vaccination may allow reasonable precautions to be taken."

But, Pardi explained, he and the other researchers included that passage because they wanted to note some potential concerns. However, he emphasized that "no scientific evidence has confirmed that these concerns are real."

It's also worth noting that the paper predated the COVID-19 pandemic by two years, so it doesn't include any information specifically about the COVID-19 vaccines.

Simply put, "there is no scientific evidence that shows that mRNA vaccines cause autoimmune diseases," Pardi said. "Multiple clinical trials have been performed with mRNA vaccines in the past 10 years and none of them found that mRNA vaccination caused autoimmune diseases. Further, we are not aware of any studies showing an autoimmune disease appearing many months after vaccination as Dr. Cole inaccurately suggests."

Likewise, Dr. Roger Shapiro, associate professor of immunology and infectious diseases at Harvard's T.H. Chan School of Public Health, told us in an email that he was unaware of any study that would support Cole's claim that the vaccines are carcinogenic.

"There is nothing in the science of mRNA vaccines that would suggest carcinogenicity, and they have been tested in humans for other diseases before COVID-19," Shapiro said. "mRNA rapidly breaks down in the body, and probably does not last long enough to act as a carcinogen."

"Regarding autoimmunity," he said, "this is always a concern with any medical product, but there is no evidence to date suggesting it, and it does not seem any more likely than with other vaccines. mRNA is made all the time in our bodies, and delivering it by vaccine should not be different."

Dr. Dean Winslow, an infectious disease physician at Stanford Health Care, concurred with the other experts with whom we spoke. In a phone interview, he characterized Cole's claims about cancer as "fearmongering" and said, "There's just no scientific basis for that."

"We're talking about these very small fragments of messenger RNA that don't hang around for long at all," he said, noting that the mRNA vaccines have been in use for almost six months and have been "very safe, very well-tolerated vaccines."

Winslow recognized that some people are concerned that the mRNA from the vaccine might persist in their bodies and somehow change their genetics or cause long-term effects. So he emphasized that the vaccines have small fragments of RNA, which survive only briefly and carry information about the virus that causes COVID-19.

Similarly, Pardi told us, "COVID-19 mRNA vaccines do not alter our DNA and they get rapidly degraded so they do not promote cancer formation."

Treatments, Vaccines Can Both Be Approved

Cole also suggested in the video that the federal government had suppressed a treatment for COVID-19 in order to "vend" a vaccine. (We'll address his claims about the supposed treatment in the next section.)

"If there's a treatment for a disease, the federal government cannot approve a vaccine by law, by rule," Cole falsely claimed, suggesting that federal agencies were withholding access to a treatment for COVID-19 so that they could instead profit from vaccines.

"So, the NIH, who, you know, is involved in approving medications, they co-hold the patent on the 'vaccine' with Moderna," Cole said, referring to the National Institutes of Health, an agency that does not approve medications. "If the fox is not guarding the henhouse there, I don't know who is. That also is insanity to have the government in bed with a private company vending a product that they want to give to everybody."

There are several problems with this statement.

First, there is no law barring vaccines if treatments are available for a given disease, said Jorge Contreras, a professor in the College of Law at the University of Utah who specializes in intellectual property and genetics and the law. He asked, "Why would there be such a law?"

Clearly there isn't, Contreras pointed out, since the Food and Drug Administration authorizes a flu vaccine every year while Tamiflu, an antiviral drug used to treat the flu, has been available since the FDA approved it in 1999.

"It's certainly true that many diseases that we vaccinate for, there is no known cure for," he said, noting that this is often the case with viral diseases, which are hard to treat.

"But that's not a legal requirement. That's a scientific reality," he said.

As for Cole's claim about the NIH, that agency conducts and funds research. It doesn't approve drugs, medical devices or vaccines — that's a function of the FDA.

The NIH did collaborate with Moderna on the development of its COVID-19 vaccine. As we've explained, government researchers had previously been working with scientists at Moderna on an investigational vaccine to protect against MERS, another disease caused by a coronavirus. The team was able to apply that knowledge to design a COVID-19 vaccine.

Since the NIH does research, it also files and receives patents, many of which it licenses to pharmaceutical companies. So, Contreras said, NIH's patents stemming from research on mRNA vaccines are to be expected, and use of those patents by pharmaceutical companies is also to be expected. Similarly, scientists from government-funded labs sometimes share credit on patents with scientists from privately funded labs. That's normal, too, Contreras said.

Generally, he explained, there are two reasons that the NIH licenses its patents to companies. First, the NIH is a taxpayer-funded institution, and it can recoup some of its investment in research by lending out the use of its discoveries. Second, the clinical trials required to bring a drug or vaccine to market are risky and expensive, so, theoretically, making its discoveries available to companies can encourage the private sector to take the risk and create products.

So, Cole mischaracterizes the relationship between the NIH and the vaccine manufacturers when he says that it's a "conflict of interest" to have the "federal government in bed with a vaccine company."

It's actually normal to have pharmaceutical companies use government-owned patents.

And he's wrong when he says of federal agencies, "they don't want a therapy to work because then they can vend their vaccine."

There's nothing that would prohibit the use of vaccines if there were an effective treatment for COVID-19.

Not Enough Data on Ivermectin

Neither the World Health Organization nor the National Institutes of Health has recommended the use of ivermectin — a common anti-parasitic medication — in the treatment of COVID-19.

Merck, the pharmaceutical company that manufactures ivermectin, has similarly noted that there is "[n]o scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies; No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and; A concerning lack of safety data in the majority of studies."

But Cole claimed in the video that ivermectin is a "treatment" for COVID-19.

He suggested that federal agencies have stifled its use so that they could profit from vaccines, as we explained above.

"We're in farm country, horse country — you know, you give it to your dogs, your cats, your horses," Cole said in the video, addressing an audience in Idaho.

Ivermectin is used to treat parasites in animals, but crossover use in humans can be dangerous. While Cole may have only been emphasizing the ubiquity of the drug, not suggesting that people should take veterinary medicine, the FDA has said that patients have been hospitalized after taking ivermectin intended for horses as interest in the drug as treatment for COVID-19 has grown.

Ivermectin does have antiviral properties, but the FDA hasn't approved it to treat any viral infections. It is being studied with regard to COVID-19, though, according to both the WHO and NIH.

"Treating COVID-19 with Ivermectin is still being evaluated in clinical trials, but at present there is not enough evidence to support its use," said Shapiro, the Harvard professor. "My understanding is that the inhibitory dose needed for it to work is extremely high and trying to take enough to suppress the virus could lead to other problems."

The trials so far have "showed no benefit or worsening disease, some showed shorter time to disease resolution or viral clearance, and some did show a possible mortality benefit; but there were problems with most of these trials that include small sample size and different outcome measures and other possible biases," he said.

Winslow, from Stanford, cautioned that "there have been many claims for miracle cures" over the course of the pandemic and said that ivermectin would need more rigorous study before we know how useful it would be in treating COVID-19.

"Ivermectin truly is a wonder drug for parasitic diseases," he said, "but my suspicion is that it will be a lot like hydroxychloroquine."

Hydroxychloroquine is an antimalarial drug that was touted by former President Donald Trump as a treatment for COVID-19, although studies found that it wasn't an effective treatment and may cause serious side effects in some patients, as we've explained before.

The problem with drugs like ivermectin and hydroxychloroquine, which are promoted as having broad-spectrum antiviral properties, is that the quantity of inhibitor required to effectively kill off the virus also sickens the host cells, Winslow said.

Even potent versions, like remdesivir, which Winslow referred to as the "gold standard" of specific antiviral therapy in COVID-19 treatments, only accelerates the time to recovery, but doesn't significantly reduce death rates or mortality from COVID-19. Remdesivir is the only drug approved by the FDA to treat COVID-19; the approval is for patients requiring hospitalization.

Cole's claim that "there is blood on the hands of bureaucrats in Washington who have suppressed this life-saving medication," is unfounded. Ivermectin hasn't been proved to be effective.

Overstating Effect of Vitamin D

Another of the major points that Cole emphasized in the video is the role vitamin D could have in fighting COVID-19.

"If you do not supplement with vitamin D in the wintertime, you are immune suppressed. Most insurance companies in Idaho and northern states do not pay for a vitamin D test, unfortunately," said Cole, whose lab offers several vitamin D tests.

After eschewing public health guidelines that recommend staying six feet apart and wearing masks to slow the spread of the virus, Cole said, "What should public health message number one, two, and three be? Vitamin D, vitamin D, vitamin D."

It's true that vitamin D, which is mostly associated with bone health, plays a part in the immune system. But that doesn't mean it's a panacea for COVID-19, as we've explained before.

While a lot of basic research points to vitamin D having a role in the immune system, it is less clear if these mechanisms are applicable in clinical practice and to what degree they would benefit COVID-19 patients, as we've written. Studies assessing whether vitamin D can treat or prevent infectious diseases have generally been inconsistent.

A recent article from NPR looked at the research on vitamin D with respect to COVID-19 over the last year and found, essentially, the same thing. It also noted that some studies have shown that low vitamin D levels are associated with a higher risk of contracting COVID-19 or with becoming seriously ill.

"While these studies raised hopes among some researchers, others are skeptical, noting that most of these are observational studies, not the gold-standard randomized, controlled trials," the story said.

"Much of the available evidence only shows association — not causation — and even those results are mixed," Walter Willett, a professor of nutrition and epidemiology at the Harvard T.H. Chan School of Public Health, told NPR.

In September, Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, said in an Instagram Live interview that for those who are deficient in vitamin D, "I would not mind recommending, and I do it myself, taking vitamin D supplements." But, as we wrote before, excessive doses should not be used.

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