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This transcript has been edited for clarity.
Welcome to Impact factor, weekly dose of comments on a new medical study. I’m Dr. F. Perry Wilson of Yale School of Medicine.
Wouldn’t it be nice if there was a treatment for COVID-19 that was safe, effective, cheap, and out of the control of faceless pharmaceutical directors who were more driven by shareholders than by patients? The dream of such a magic bullet led to a number of similar claims that a certain drug – or supplement, in some cases – has dramatic effects against COVID-19. I saw it first with hydroxychloroquine, but a similar hype surrounded vitamin D, ivermectin, melatonin, vitamin C and, of course, zinc.
What made the claims so convincing were two things. One was a dose of biological plausibility. Biologists could argue that there is a underlying reason Why a certain vitamin would help, usually citing beneficial effects on immune function or a reduction in inflammatory cytokines. But more than that, these drugs had a subdog story. These modest agents who have been with us for decades or more could become our strongest ally against this scourge of a virus. Preliminary data were often breathless, but, as I pointed out in terms of vitamin D, I was burned before. Many of us wanted to see randomized studies before engaging in any of these potential remedies.
This week, I received such a lawsuit, which appeared in JAMA Network Open, on the ability of zinc and vitamin C – alone or in combination – to shorten the symptoms of COVID-19 in outpatients.
This was a 2 x 2 factorial design, as you can see here. Patients were randomized to routine care or to one of the three treatment arms in an approximately equal manner.
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These were outpatients, so we weren’t going to see a lot of hard results. Rather, the researchers used a method of scoring symptoms based on rank. Each day, participants were asked about four symptoms, which they rated on a scale of 0 to 3, giving a symptom score of 0-12. The main result was the time until the symptom score was halved; in other words, if you start at 4, the time required to reach 2; or if you start at 10, the time it takes to get to 5. This is a rather strange result, because it assumes a mathematical equivalence in which I do not think it exists, but I suppose it is as good as we can get.
Here are the symptoms over time for the entire study cohort. You may notice a general decrease in moderate symptoms (yellow) in favor of mild symptoms (green).
Thomas S et al. JAMA Netw Open. 2021; 4: e210369. doi: 10.1001 / jamanetworkopen.2021.0369
But when you stratify after treatment, the time to reduce symptoms by 50% was practically the same in general: about 5.5 to 6.5 days, depending.
Thomas S et al. JAMA Netw Open. 2021; 4: e210369. doi: 10.1001 / jamanetworkopen.2021.0369
No individual symptoms resolved faster with zinc, vitamin C or the combination. Basically, the population looked as we expected: a few days of fever, with persistent cough and fatigue.
The hospitalization rate did not differ significantly, although it was slightly higher in the supplement groups. And, fortunately, there were only three deaths – one in the vitamin C group and two in the combined group.
As for the side effects, there was nothing crazy about it. But obviously, the authors saw more in the treatment groups than in the regular care group, mainly things with GI.
Now, zinc apologists will no doubt notice the lack of a zinc ionophore (such as chloroquine or pyrithione), which is why this did not work. And again, I remind everyone that biological plausibility is not the end of medical research, but the beginning; it is the minimum bar to pass to ethically carry out a definitive process, not an end in itself. I will be happy to read any imminent randomized hydroxychloroquine-zinc study that occurs.
More generally, I think we just have to accept that a remedy for COVID is quite unlikely to stay in our closets. Many chemicals have activity against pathogens in test tubes, just as a lot of things work in vitro against cancer. But this process reminds us that, most of the time, promising biological agents do not survive the rigors of real-world testing. Keep hope, but bring data.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His scientific communication work can be found in the Huffington Post, on NPR and here on Medscape. He sends a tweet @fperrywilson and hosts a repository of his communication works at www.methodsman.com.
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