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This transcript has been edited for clarity.
Welcome to Impact factor, your weekly dose of feedback on a new medical study. I’m Dr. F. Perry Wilson of the 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 executives who were more obligated to shareholders than patients? The dream of such a magic bullet has led to a number of similar claims that a particular drug (or supplement, in some cases) has dramatic effects against COVID-19. We saw it first with hydroxychloroquine, but with a similar hype surrounded by vitamin D, ivermectin, melatonin, vitamin C, and of course zinc.
What made the claims so compelling were two things. One was a dose of biological plausibility. Biologists could argue that there was some underlying reason Because a certain vitamin would help, usually citing beneficial effects on immune function or a reduction in inflammatory cytokines. But on top of that, these drugs had something of a helpless history. These modest agents who were with us for decades or more could become our most powerful ally against this scourge of a virus. Preliminary data used to be published without breathing, but, as I pointed out in terms of vitamin D, we had been burned before. Many of us wanted to see randomized trials before committing to any of these possible cures.
This week we have obtained a judgment of this kind which appears in JAMA Network Open, analyzing the ability of zinc and vitamin C, alone or in combination, to shorten COVID-19 symptoms in outpatients.
It 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 approximately the same way.
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These were outpatients, so we weren’t going to see a lot of difficult results. Rather, the researchers used a range-based scoring method. Each day, participants were asked about four symptoms, which they rated on a scale of 0 to 3, giving a symptom score range of 0-12. The main result was time to halve the symptom score; in other words, if you start with a 4, the time it takes to get to 2; or if you start at 10, the time it will take you to get to 5. This is a bit of a weird result, as it assumes some mathematical equivalence where I don’t think it exists, but I guess it’s as good as we can get.
These are the symptoms over time for the entire study cohort. A general decrease in moderate symptoms (in yellow) can be observed in favor of mild symptoms (in green).
Thomas S, et al. JAMA Netw Open. 2021; 4: e210369. doi: 10.1001 / jamanetworkopen.2021.0369
But when stratified by treatment, the time to 50% reduction in symptoms was basically the same overall: 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 more quickly with zinc, vitamin C, or combination. Basically, the population seemed to be waiting: 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 usual care group, mostly GI things.
Now, zinc apologists will no doubt notice the lack of a zinc ionophore (like chloroquine or pyrithione) because it didn’t work. And, again, I remind everyone that biological plausibility is not the end of medical research, but the beginning; it is the minimum that must be overcome to ethically carry out a final judgment, not an end in itself. I will be happy to read any upcoming random hydroxychloroquine-zinc assays that come out.
Broadly speaking, I think we just have to accept the fact that there is very unlikely to be a cure for COVID in our closets. Many chemicals have activity against test tube pathogens, just as many things work in vitro against cancer. But this essay reminds us that biologically promising agents often do not survive the rigors of real-world testing. Keep hoping, but provide data.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of the Yale Clinical and Translational Research Accelerator. His scientific communication work can be found in the Huffington Post, NPR and here at Medscape. Make a tweet @fperrywilson and hosts a repository of his communication work at www.methodsman.com.
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