I was not planning to revisit this topic just yet, but President Trump has forced the issue with his mention yesterday that he’s taking hydroxychloroquine. Let’s try to keep this short: does any regular reader here actually wonder what I might think about that? I know that the comments section here gets swarmed with people banging the HCQ drum – and the azithromycin drum, the zinc drum, and the rest of the percussion section – but I don’t think even most of those folks think that it’s much of a prophylactic. There’s a lot of talk from the fans of this treatment about how you have to give it early in the course of the disease, but how many of you folks think it’s a preventative? There’s no evidence of that, you know. Even if you think that there’s a ton of evidence for HCQ combinations as coronavirus treatments (and we disagree there), there’s no evidence whatsoever as a prophylactic. Come on.
So it’s been two weeks since that post, which is the last time I looked over the field. What’s happened since then? Well, there’s this preprint from a group in Madrid, an observational study over 164 coronavirus patients there. The team found that the mildest-affected cohort (at admission) seemed to show a benefit from early hydroxychloroquine treatment. But a comment to this paper has noted that the non-HCQ patients in the (retrospective) group actually showed higher levels of cardiopathy, dementia, and lymphopenia, so there’s a real question about comparability.
We also have this retrospective study from Northwell in New York, on 201 patients that were treated with various combinations of chloroquine, hydroxychloroquine, and azithromycin. The paper looks at QT prolongation, the cardiac side effect that’s been discussed so much. QT prolongation increased significantly in the drug combination group (as others have reported as well). Seven patients had to discontinue therapy due to cardiac effects, but there were no life-threatening Torsade de pointes incidents, fortunately.
There are others. But rather than do these retail, here’s a review of everything in the literature on COVID-19 and hydroxychloroquine treatment up to May 13. It summarizes eleven studies (3 controlled trials and 8 observational/retrospective efforts), totaling 2354 patients receiving HCQ (alone or in combination) and 1952 controls. Overall, there was no difference in viral clearance. No difference in symptomatic improvement. No difference in overall mortality. The only clear difference between the two groups was in adverse effects, which were (on again) higher in the HCQ treated population.
How about since May 13? Well, here’s an open-label randomized study from China in February and March (75 patients getting HCQ plus standard of care, 75 getting standard of care). They were looking for viral clearance by 28 days, and found no difference between the two groups, with more adverse effects in the HCQ treatment group (diarrhea and blurred vision, mostly). It does not appear that they took ECG data to look for signs of QT prolongation. And here’s an observational study from France, 181 patients who were on oxygen but not in the ICU. There were no significant differences in survival rate, transfer to ICU care, or continued use of supplemental oxygen between the patients who received HCQ and the ones who had standard of care treatment. But ten per cent of the patients in the HCQ group had to discontinue the drug due to cardiac side effects as shown by ECG monitoring. It’s safe to say that neither of these studies would modify the conclusions of the review of the literature up to the 13th.
Update: here’s a preprint from NYU on the combination of HCQ/azithromycin and HCQ/azithromycin/zinc. To the best of my knowledge, this is the first study to look at this under any sort of controlled conditions. It’s a retrospective of 411 patients with the addition of zinc sulfate (220mg, b.i.d.) and 521 on the dual combination without it. Let me quote from the paper directly:
In univariate analysis, the addition of zinc sulfate to hydroxychloroquine and azithromycin was not associated with a decrease in length of hospital stay, duration of mechanical ventilation, maximum oxygen flow rate, average oxygen flow rate, average fraction of inspired oxygen, or maximum fraction of inspired oxygen during hospitalization (Table 2). In bivariate logistic regression analysis, the addition of zinc sulfate was associated with decreased mortality or transition to hospice (OR 0.511, 95% CI 0.359-0.726), need for ICU (OR 0.545, 95% CI 0.362-0.821) and need for invasive ventilation (OR 0.562, 95% CI 0.354-0.891) (Table 3). However, after excluding all non-critically ill patients admitted to the intensive care unit, zinc sulfate no longer was found to be associated with a decrease in mortality (Table 3). Thus, this association was driven by patients who did not receive ICU care. . .
After looking for any other effects, the authors conclude that “After adjusting for the timing of zinc sulfate treatment, the associations between zinc and the need for ICU and invasive ventilation were no longer significant but we did still observe a trend.” They regard this as the first evidence that zinc might be beneficial in this treatment, but your own mileage may vary.
So once again, the evidence for benefit is weak and the evidence for adverse events is much stronger. Over and over we see similar results. Cue the folks in the comments, though, saying that none of that matters, ’cause these folks didn’t use zinc and they didn’t start early and they didn’t do the other stuff. Well, there are more clinical trials underway and more reports set to come out shortly, and if the data so far are any indication, you’ll all get the chance to try to explain their results away, too. As for you zinc folks, all I can say is see if you can get word to the White House, because
I’ll bet that Trump isn’t doing it right, either. Update: apparently he’s said that he’s taking zinc, too and an “initial dose” of azithromycin. Oh joy.
As for the President himself announcing that he’s taking a drug that has not been proven to help patients with the disease, and that he’s taking it prophylactically (he is, right?) even though there’s even less evidence for that. . .and that the White House physician’s statement from last night doesn’t even resolve whether or not hydroxychloroquine has even been prescribed or whether or not Trump is actually even taking it for real (you never know), well. . .I could go on about all this, but what’s the point? My opinion of Donald Trump, his worldview, his judgment, his public statements, and his behavior are a matter of record. God knows this latest news doesn’t change my mind. And it won’t change the mind of any of the people who like all those things, either, of course. The time for arguing about Trump is long past. November’s coming. What will the US, and the world, look like by then? What will it look like after the election? That’s the argument. That’s when all these things will be settled.