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An anti-parasitic versus COVID-19

Could ivermectin be effective against the coronavirus?


A man shows a container of ivermectin capsules as he comes out of a pharmacy in Santa Cruz, Bolivia in May 2020. Rodrigo Urzagasti/picture alliance via Getty Images

An anti-parasitic versus COVID-19
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Amid the COVID-19 pandemic, researchers have faced intense pressure to find effective treatments quickly. One response has been to check whether drugs already used for other diseases might be helpful—an approach called drug repurposing. It saves time, since safety tests for existing drugs are already completed and tolerable dosages identified: Researchers only need to learn whether any of those medications could also help against the coronavirus.

Such drug repurposing for COVID-19 has been mixed so far, with one major success and one likely failure. Next at bat: ivermectin, an anti-parasitic discovered long ago. Could it help against COVID-19, as a peer-reviewed study published last month has suggested?

As we reported in June, the repurposed steroid dexamethasone was proven to help some COVID-19 patients. Dexamethasone enables patients’ immune systems to fight the coronavirus while avoiding a potentially fatal overreaction. It’s recommended only for hospitalized patients, though, because it’s not helpful in early stages of COVID-19 and can be harmful if given too early.

Another prominent drug repurposing effort did not succeed: We had high hopes for hydroxychloroquine, or Plaquenil, after initial studies suggested it was effective against COVID-19. But the U.K’s large-scale Recovery trial showed conclusively that the drug didn’t help. (When President Trump contracted COVID-19 last October, hydroxychloroquine was not among the drugs he received.)

More recently, interest has surged in the anti-parasitic ivermectin. This cheap and ubiquitous ingredient in dog dewormers had attracted researchers’ attention, but the largest research trial last year supporting ivermectin use was retracted amid the Surgisphere scandal and suspicions of falsified data. Stateside interest in ivermectin faded—but the odd episode wasn’t the fault of the drug, which has a reputation as a safe and effective treatment for parasitic infections in the developing world.

But does it work against the coronavirus? It does work in vitro (“in glass”)—i.e., in lab experiments. But in that context it also kills the dengue virus, and yet a phase 3 trial in Thailand failed to demonstrate the drug’s benefit against dengue fever in people. That’s likely due to concentration: There’s little downside to trying higher concentrations of an active ingredient in a lab, but in living people higher concentrations mean potentially unsafe doses. With dengue fever, ivermectin doses people could tolerate weren’t enough to help against the virus.

Research in people, then, is where we learn whether ivermectin is a valuable tool or not. Up to this point, most of the research on ivermectin and COVID-19 has been of low quality. Much of it was never published beyond free online research sites, and what little was peer-reviewed often appeared in questionable, pay-to-publish journals. A few efforts have presented themselves as meta-analyses, which weigh multiple existing studies on a given topic, but they’re only as good as their ingredients.

This predicament started to change with a study published in the January issue of the respected journal Chest. Doctors treated 173 COVID-19 patients with ivermectin and found that they were less likely to die than patients who didn’t get the treatment.

The authors of the Chest paper resisted making too much of their preliminary findings and acknowledged their study’s limitations frankly: It was a retrospective, nonrandomized look at a relatively small group of patients. The authors agreed that ivermectin shows enough promise to deserve large-scale clinical trials, and they emphasized that “further studies in appropriately designed randomized trials are recommended before any conclusions can be made.”

Ivermectin is generally considered safe, so one might fairly ask what harm there is in trying it. That depends: If a given person is already sick, then the “may help, probably won’t hurt” logic might apply. But if the hope is that ivermectin will quickly take us back to life circa 2019, that’s a very big if.

Only future high-quality research can provide those answers. Like the authors of the Chest study, I look forward to seeing that research.


Charles Horton, M.D. Charles is WORLD's medical correspondent. He is a World Journalism Institute graduate and a physician. Charles resides near Pittsburgh with his wife and four children.

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HANNAH.

Here’s more unfiltered news on covid-19 from the Association of American Physicians and Surgeons.

KSH8386

Can you please add an article on prophylaxis? Isn't it more important in a pandemic to stop the spread to the whole population than to treat the few victims? ("an ounce of prevention...") Studies I have seen are clear that both HCQ and Ivermectinm dramatically reduce the transmission of coronavirus.

Tim Miller

Steve, I also appreciate the depth and clarity of your response. Thanks for sharing that with us.

CJ

Steve, thank you for your thoughtful and thorough response. 

Steve Shive

Thank you for this article. I appreciate your balance and clear explanation of the value of various types of research studies trials since there is so much hype about various potential cures or, at least, helpful treatments. Retrospective studies, and observational research, give hope and guidance for designing more accurate and reliable controlled trials. No more. But they are useful in that they can be used to help design more reliable clinical trials that could potentially give us more trustworthy data driven therapies.

The two comments I see so far to this article are from retrospective observational studies. The NIH Ivermectin link (as noted is from August 2020) makes clear the significant limitations to the data and results at that point in time. The same data (essentially) and research just reported in "Chest" (peer-reviewed) using ivermectin as well as the older online NIH report (not peer reviewed) of the same population give different numbers in the "control" group, 107 vs 103. Not a big deal. But the peer-reviewed and analyzed data presented in "Chest" give a much better presentation and explanation of the data. More importantly they not only give possible positives they also show  a clear explanation of the very real potential for confounding study bias of the results. This should be read by all before commenting. Go to the link in this World article which gives the abstract. Then click on the hyperlink to the full article. Scroll to the bottom for "Interpretation" which I find is often the best place to start. Also note the "number needed to treat" (NNT) is 9. Thus 9 patients need to be treated for one to give a positive response with an absolute risk reduction of 11.2%

Typical of retrospective non-randomized studies there are a number of confounding variables that make the results less reliable for giving clinical treatment guidance.

Additionally, The nursing home study that is mentioned, besides being non-randomized and not placebo controlled, also included treatment with zinc and azithromycin. So why say it was hydroxychloroquine that made the difference? If there truly was a difference. There is no control group so we cannot extrapolate those findings to the general public. 

TGE6325

Looks like you are a few months late with this story. AP finally got around to covering it so WNG did too?

https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/ivermectin/

Salty1

There have been a number of reports that show the hydroxychloroquine treatment worked. Here is one report at a nursing home in Texas.

JHIL2053Salty1

Did you intend to provide a link