Effect of treating Covid-19 with hydroxychloroquine with azithromycin

From the abstract:

> Results

> The initial search yielded 839 articles, of which 29 articles met our inclusion criteria. All studies except one were conducted on hospitalized patients and evaluated the effects of hydroxychloroquine with or without azithromycin. Among the 29 articles, 3 were randomized controlled trials (RCT), one was a non-randomized trial and 25 were observational studies, including 10 with a critical risk of bias and 15 with a serious or moderate risk of bias. After excluding studies with critical risk of bias, the meta-analysis included 11,932 participants for the hydroxychloroquine group, 8,081 for the hydroxychloroquine with azithromycin group and 12,930 for the control group. Hydroxychloroquine was not significantly associated with mortality: pooled Relative Risk RR=0.83 (95% CI: 0.65-1.06, n=17 studies) for all studies and RR=1.09 (95% CI: 0.97-1.24, n=3 studies) for RCTs. Hydroxychloroquine with azithromycin was associated with an increased mortality: RR=1.27 (95% CI: 1.04-1.54, n=7 studies). We found similar results with a Bayesian meta-analysis.

>

> Conclusion

> Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19 patients but the combination of hydroxychloroquine and azithromycin significantly increased mortality

Something I personally would find helpful is if someone with the appropriate background could talk through these results and some of the acronyms.

This passage is quite dense, and I think I and - hopefully I'm underestimating the audience on HN - others would have difficulty parsing it:

> After exclusion of studies with critical bias, the pooled RR for COVID-19 mortality was 1.27 (95%CI: 1.04-1.54, n=7) indicating an increased mortality linked to the use of hydroxychloroquine with azithromycin. With a baseline hospital mortality of 26%, we identified a significant absolute risk difference of +7%. We found an increased risk of mortality in patients treated with hydroxychloroquine and azithromycin compared to standard of care (RR: 1.29 (95%CI: 1.06-1.58, n=6)) among non-randomized studies but this relationship was not found in the single Brazilian RCT, with no heterogeneity observed across the study design (Pheterogeneity between = 0.28) (Figure 3). There was a low heterogeneity across the included studies (I2 =38%, p=0.14). Egger's test (p= 0.70) and Begg's test (p=0.65) were not significant but the asymmetry in the funnel plot indicates that a publication bias could be present (Figure S7). However, the number of included studies was small. Subgroup analyses are described in supplementary material (Table S4, Figure S8). The Bayesian meta-analysis led to similar results with a pooled RR for mortality of 1.32 (95%CI: 0.97-1.68, n=7 studies) (Table S5, Figure S9). The increase in mortality was also significant with influence analysis (Figure S10).

RR is relative risk, HR is hazard ratio, OR is odds ratio. Are there any red flags in reading this, and how relevant is it that studies were excluded for critical bias, that the single randomized controlled trial did not show this relationship.

The number of studies of HCQ with AZI was also quite small - is that a problem, and how likely is it that we could expect further studies to point in the opposite direction? 5% likely? More or less?

Lastly, many HCQ proponents advocate zinc in this mixture. That wasn't included in this meta-analysis. Is there a clinical basis for believing zinc changes the therapeutic effect of HCQ and AZI?

>Hydroxychloroquine alone was not associated with reduced mortality in hospitalized COVID-19 patients but the combination of hydroxychloroquine and azithromycin significantly increased mortality.

So many studies showing what we already knew. It really worries me how much science seems to be dictated by fashion these days...

Not a study or experiment but a "meta-study" where an attempt is made to merge data from many different experiments and form some conclusions. They started with 839 studies and, in the end, used data from only 29 of those studies to draw conclusions.

Two obvious flaws:

1. "All included studies except one (Skipper et al.) were carried out on hospitalized patients". This means all patients got HCQ very late. But the recommended course for HCQ has always been to give it early at first symptoms and to never wait until hospitalization. In the "selected" experiments of this meta-study all patients were hospitalized prior to receiving HCQ, far too late for it to do it's magic.

2. "Mean (SD) age of participants was 62.1 +/- 8.5 years." The patients chosen were near elderly or elderly, those most likely to die from covid.

So they set up a meta-study by cherry-picking experiments having populations of elderly patients who were provided HCQ treatment only after hospitalization. That is, choose the weakest patients who were treated at the last possible moment and include only those patients in your meta-study.

Finally, at the end of their paper they state "Our results suggest that there is no need for further studies evaluating these molecules," In other words, thanks to this meta-study no further studies, not even the "golden standard" randomized controlled trials are required to "know" that HCQ doesn't work! The meta-study's authors see all, know all, and know best even though they haven't done a study or trial nor examined a single patient for this meta-study. The chutzpah of these authors is astonishing!

But just as in the movie "Wizard of Oz" Dorothy is instructed to "Pay no attention to that man behind the curtain!" we must ask just who IS the "man behind the curtain"? There is a hell of a lot of money (trillions projected) that wants to put the hush to HCQ so that big pharma can sell us an expensive vaccine! Remember what has happened in the recent past:

"What Is Gilead's Role In The War On Hydroxychloroquine?"

https://www.zerohedge.com/medical/what-gileads-role-war-hydr...