The reason I'm interested in hydroxychloroquine and chloroquine is many people are claiming that these are effective against the coronavirus because they help bring zinc into cells, and the zinc kills the virus, and others have argued that since quercetin and EGCG do the same thing, these also would be effective for prevention or treatment of the coronavirus. If quercetin or EGCG should be effective in this way, I would want to add them to the protocol I use in The Food and Supplement Guide for the Coronavirus.
The first step, then, was to figure out if hydroxychloroquine or chloroquine are actually effective.
Chloroquine is a drug long used to treat malaria. Hydroxychloroquine is a closely related compound that has also been used to treat malaria, but more recently has been used to treat autoimmune conditions such as lupus and rheumatoid arthritis.
More recently these drugs have been shown in vitro (in a test tube, not a living organism) to have a broad spectrum of antiviral activities. Although they have never been shown to have clear antiviral activity in humans against any virus, they have become widely used in China to treat COVID-19.
The potential of these drugs to treat COVID-19 received a lot of hype from Donald Trump recently. As a result, out of fear of the virus and hype over chloroquine, a Phoenix man and his wife drank a fish tank cleaner containing chloroquine phosphate. The man died and the wife wound up in critical care.
Is the hype deserved?
As reviewed in “Of Chloroquine and COVID-19,”
- “To date, no acute virus infection has been successfully treated by chloroquine in humans.” It failed to treat flu or dengue in humans.
- For chronic viruses, the results in HIV have been inconclusive, and the results with hepatitis C have been so slight that it's never become part of a standard protocol.
- Although chloroquine has been shown to be antiviral in vitro against SARS-CoV-2, the cause of COVID-19, it also proved antiviral in vitro against chikungunya virus, yet acted as a proviral toward chikungunya in living mice. This might be because it can suppress the immune system and might relate to the effectiveness of hydroxychloroquine as a treatment for autoimmune disorders. Could it also make COVID-19 worse?
- Despite the widespread use of chloroquine and hydroxychloroquine to treat COVID-19, there are as yet no randomized controlled trials clearly showing it is effective.
A “Systematic Review on the Efficacy and Safety of Chloroquine for the Treatment of COVID-19” suggested similar caution. The authors performed a comprehensive search for everything related to the topic and found very little that had already been published: an in vitro study, two letters, a consensus panel of Chinese experts, a Dutch national guideline, and an Italian national guideline. 23 Chinese trials had been registered, but as of March 10 when this was published, none of the data had been released.
That the expert opinion was running far ahead of the data is demonstrated in this quote from the paper:
A narrative letter by Chinese authors reported that a news briefing from the State Council of China had indicated that “Chloroquine phosphate… had demonstrated marked efficacy and acceptable safety in treating COVID-19 associated pneumonia in multicentre clinical trials conducted in China.” The authors also stated that these findings came from “more than 100 patients” included in the trials. We sought for evidence of such data in the trial registries we reviewed and found none.
As I reviewed the other day, a non-randomized French trial of hydroxychloroquine suggested the drug virologically cured 15 out of 26 people, while it nauseated one, put three in ICU, and killed one. Because it wasn't randomized, it isn't clear whether the cure or the worsening represent true effects of the drug, but if we are to regard the cure as a real effect, we also have to regard the worsening as a real effect, suggesting that if it works it might have a high risk profile.
A Chinese randomized controlled trial found no difference at all between the use of hydroxychloroquine and standard treatment. The standard treatment was bed rest, oxygen inhalation, symptomatic support, neubulized interferon, lopinavir and ritonavir (two antivirals), and, when necessary, antibacterials. The two antivirals in the standard treatment have also been shown to have no effect against another “standard treatment” in another randomized trial (hat tip to Avi for this study). In that trial, the standard care was supplemental oxygen, ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO). So, none of the antivirals did anything beyond the oxygen therapy and other support in the list.
The World Health Organization is launching a multinational set of trials testing the efficacy of interferon, chloroquine, lopinavir, and ritonavir. This should provide us with some information, but right now a lot of things are being thrown at COVID-19 with no clear evidence they are effective.
That WHO is launching this trial should also help allay rational fears that Chinese data can't be trusted. After all, China just expelled all the American journalists, so it's clear the Chinese government doesn't value transparency around the COVID-19 situation.
So, are hydroxychloroquine or chloroquine effective?
I'd bet it at 50/50 odds, at best. Hyping them as saviors is nuts.
I also find it ironic that many people will beat the “trust the experts” drum endlessly, bashing anyone suggesting nutrients or herbs could be relevant, yet vitamin D, elderberry, and garlic have all been shown to have antiviral effects in humans, yet hydroxychloroquine and chloroquine have not. Why do these drugs get special status just because the experts are using them with no evidence of their efficacy?
In any case, what, if anything does this say about quercetin? I'll let you know over the next couple of days.
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