We don’t know if hydroxychloroquine is safe for COVID

Hydroxychloroquine (and related drug chloroquine) has been in the news a lot lately for its supposed ability to cure or prevent COVID-19. These drugs are commonly used to treat autoimmune diseases lupus and rheumatoid arthritis, especially under the brand name Plaquenil (hydroxychloroquine).

This leaves those of us with autoimmune conditions wondering: could I be taking hydroxychloroquine to both treat my autoimmune disease and prevent coronavirus? In a time when taking immunosuppressants is unnerving, is hydroxychloroquine a safe treatment? If I’m not on hydroxychloroquine, should I start taking it?

The short answer is no. The long answer is that a lot of studies are showing contradictory results, and the small study I covered in a previous article found worse outcomes for people with COVID-19 who were taking hydroxychloroquine for autoimmune conditions. In the absence of larger, better studies, caution is best.

Unfortunately, the premature hype around hydroxychloroquine is causing shortages that make it hard for lupus patients to get the drug that keeps them alive. PLEASE don’t take this drug away from people who need it to control life-threatening autoimmune disease. There’s not enough evidence hydroxychloroquine will protect anyone from coronavirus, and the hysteria and unnecessary prescriptions are interrrupting autoimmune treatment at a very dangerous time.

What are hydroxychloroquine and chloroquine?

Chloroquine and hydroxychloroquine are drugs whose primary use is in treating malaria. However, because they have immunosuppressant effects, they’re also used to treat autoimmune conditions like lupus and rheumatoid arthritis (RA). People with RA take hydroxychloroquine to prevent pain, disability, and permanent joint damage, while people with lupus take it to prevent pain, organ failure, and death.

So what’s the difference between chloroquine and hydroxychloroquine? As you might be able to guess from the names, the drugs are similar, right down to their structure. In fact, the only difference is the addition of a hydroxyl group (an oxygen and hydrogen) on the tip of hydroxychloroquine. Hence, the name hydroxychloroquine!

Chloroquine (C₁₈H₂₆ClN₃) on the left, and hydroxychloroquine (C₁₈H₂₆ClN₃O) on the right. They’re identical except for the hydroxyl group (OH) on the end of hydroxychloroquine.

I’d only ever heard of hydroxychloroquine, which goes by the brand name Plaquenil. It’s preferred over chloroquine because it’s safer and less toxic in the event of accidental overdose.

Hydroxychloroquine and COVID

People latched on to hydroxychloroquine as a COVID treatment because early studies of hydroxychloroquine and COVID-19 in vitro showed positive results. The problem is that in vitro results don’t necessarily translate to the human body.

An experiment performed in vitro (literally: in glass) is carried out in a culture dish, not in an organism’s body. The drug can be applied directly to the cells in question, in whatever concentration is desired, and it only interacts with the cells you allow in the dish. When a drug is administered to a person, however, it may take an overdose to reach the same concentrations. Or the drug might be broken down or used by the body in ways that make it ineffective. Or the body might respond to the changes caused by the drug by negating its effects.

While chloroquine inhibits COVID’s growth in vitro, when it was given to mice with coronavirus, it didn’t inhibit the virus’s replication. In fact, past research on chloroquine for other viral infections has shown harmful effects, despite positive in vitro results.

So what about studies on real patients with COVID-19? A French study with a small sample size (42 patients) showed reductions in viral load for patients given hydroxychloroquine, some with the antibiotic azithromycin. This was hailed as proof of the usefulness of the drug. However, the researchers excluded 6 of the sicker study participants from the results for no clear reason, leading to retroactive criticism from the very society that published the study. Another hospital in France tried to replicate the results and failed. Perhaps most concerning, a study of hydroxychloroquine use with azithromycin found that using both drugs doubled the risk of death due to heart failure.

A small (62 patient) randomized control study in Wuhan showed shorter time to recovery for patients taking hydroxychloroquine. A similar small (30 patient) study in Shanghai found no difference between patients treated with hydroxychloroquine and other treatments. Concerningly, a study in Brazil had to be ended early because of heart problems and higher mortality among severe COVID patients treated with high doses of chloroquine.

An observational study in New York City with a large sample size (1440) showed no positive or negative affects for COVID patients given hydroxychloroquine. Neither did a retrospective analysis of 181 COVID patients in France. The gold standard of medical research is the randomized control trial, and the largest randomized control trial to date, done in China with 150 patients with mild or moderate COVID, showed that hydroxychloroquine didn’t reduce the time it took for someone to clear the virus from their system.

In summary, no study on hydroxychloroquine for COVID-19 is perfect right now. It’s too early. But some of the best and largest studies show that hydroxychloroquine doesn’t improve COVID outcomes and can cause significant side effects.

Update 5/22/20: A just-published observational study of 96,032 patients worldwide has found that patients taking hydroxychloroquine or chloroquine (with or without azithromycin or other antibiotics) had increased death rates while hospitalized compared to those given standard treatments. Also, patients taking hydroxychloroquine or chloroquine (with or without antibiotics) were more likely to have heart arrhythmias.

Update 6/10/20: The Lancet has retracted the paper discussed above. Some people aren’t sure that the data used even exists. It’s quite a scandal. The other studies discussed here still stand, though.

What does that mean for us?

If you’re considering hydroxychloroquine for COVID prevention, it likely isn’t worth the dangerous side effects (and potentially worse COVID outcome). Especially if you’re taking it without the supervision of a doctor, you face the risk of complications and overdose. The biggest complication reported in studies is heart problems, but people taking Plaquenil for lupus and RA must also be monitored for signs of vision loss and liver failure. And never, ever take non-pharmaceutical forms of chloroquine.

There’s also no particular reason to switch to hydroxychloroquine as treatment for autoimmune disease. In fact, it’s probably safer to be taking other treatments like biologics right now, according to data from an IBD database and a small New York case series that were largely in agreement. Biologics are targeted medications that modulate specific parts of the immune system, instead of causing more widespread suppression.

This doesn’t mean you should stop a medication you’re on for autoimmune disease. Always talk to your doctor, because stopping medication can cause a disease flare. During a flare, you may be more vulnerable to infections like COVID.

Shortages of a life-saving drug

Unfortunately, the media hype is already out of the bag. People are taking the US president’s claims to heart, and prescriptions for hydroxychloroquine have been elevated for months. As early as March, autoimmune patients were facing signs that they wouldn’t be able to get hydroxychloroquine to treat their own conditions. Some were even thanked for “their sacrifice”—one that, it’s becoming apparent, didn’t need to happen.

If you’re facing this issue or are worried about it in the future, the Arthritis Foundation has advice that may help. It’s recommended to try to get a 90-day supply, and you can also try contacting your state pharmacy board or out-of-network pharmacies.

However, lupus disproportionately effects people in lower socioeconomic classes, so any increase in cost could make it impossible for them to get the drug. This is why it’s so important to not drive up demand for hydroxychloroquine when there’s no evidence it works against COVID.

I’ll be on the lookout for more studies in the future, but right now, nothing supports taking hydroxychloroquine to prevent or treat COVID-19. For more information about COVID and autoimmune disease, you can check out my articles on biologics and coronavirus and data on immunosuppressant use with COVID-19.

Stay safe, everyone.

-Bri

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