First hydroxychloroquine randomized controlled trial: results disappointing
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What happened in essence is that almost all cases were mild so the patients almost all got better after a while, with or without medication. This doesn't mean HCQ is ineffective, only that its efficacy couldn't be measured in this instance. And I wouldn't call a study where almost everyone gets better at the end "disappointing".
The median age of the dead in Italy is 80.5 and 99.2% of them were sick, averaging 3 comorbid conditions [3]. So basically the opposite of that.
[1] https://twitter.com/AndyBiotech/status/1241741127205572609?s...
[2] https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm
[3] https://www.google.com/amp/s/www.bloomberg.com/amp/news/arti...
i.e., would the age curve be different in an ideal situation where everyone was getting optimal care, and is the statistic thus misleadingly suggesting that younger people are less at risk?
As an aside, you were certainly not being judgmental about the clinicians in Italy and I applaud you for that. Those professionals are doing incredible work in unbelievably difficult and personally dangerous situations, so I hope we can all agree not to second guess their decisions from the cheap seats.
I was trying to point out that some people using the statistics about age and mortality from Italy are trying to use them as justification for doing less to combat the disease's spread, and that might be a dangerously misleading gambit.
This is a summary of all cases in Colorado. All of our state's (small handful of) fatalities have been among residents aged 60 and over. The hospitalization rate is ~5% or so for adults in the 30-50 year old range, and it rises to about 20% in the elderly age groups.
Caveats: with only 600 cases to draw inferences from, there's a little less than one digit of precision in those estimates. Testing availability is also still somewhat limited in the state with a little more than a 10% positive rate.
I think if your population trends younger this can mean pretty high absolute numbers even if low percentages. A number of news sites in various places said the under 50 crowd is using significant portions of hospital resources.
Nationally, 12 percent of the intensive care patients were between the ages of 20 and 44.
https://www.nytimes.com/2020/03/23/nyregion/nyc-coronavirus-...
> Nationally, 12 percent of the intensive care patients were between the ages of 20 and 44.
Versus 26 percent of the ICU patients being aged 45 to 54, and 62 percent of the ICU patients being 55 or older.
https://statmodeling.stat.columbia.edu/2020/03/07/coronaviru...
https://www.statista.com/chart/21173/hospitalization-icu-adm...
Where do you get that idea from? In the study it looks like everyone got better, but that may just be regression to the mean (i.e. the normal progression of covid-19 in those patients).
If you'd want to know if placebo is effective on covid-19 you'd have to do a completely different study, comparing placebo to doing nothing. Though the likelyhood that placebo therapy is "pretty effective" here is very low. Placebos usually work best in things that have a strong subjective factor, e.g. pain treatment.
This is a moot point, because the French study was not a randomized control trial, on 6 people, at different stages of the disease from this study.
> Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion5. In addition, CQ could inhibit SARS-CoV entry through changing the glycosylation of ACE2 receptor and spike protein6. Time-of-addition experiment confirmed that HCQ effectively inhibited the entry step, as well as the post-entry stages of SARS-CoV-2, which was also found upon CQ treatment (Supplementary Fig. S2).
[1] https://journals.plos.org/plosone/article?id=10.1371/journal...
[2] https://journals.plos.org/plospathogens/article?id=10.1371/j...
https://www.ncbi.nlm.nih.gov/pubmed/27927040
Course, that'll only work if the symptoms are being caused by an overactive immune system and it's able to mediate that immune response in time.
Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome [1]. HCQ is known to moderate this reaction.
[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
With any chemo drug I suspect it won't have a huge effect on patients who are mild, in fact it could have a negative effect, but I'm no expert.
https://en.wikipedia.org/wiki/Chemosensitizer
edit: It's still being researched, but it is an anti-cancer drug, just like how chemo drugs get classed.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2...
Chemo drugs aren't really a technical category, but it seems like chloroquine will become part of the anti-cancer family soon.
Given our recent discovery that chemotherapy has only gives you a 2% greater chance of survival (again, your immune system fights of cancer just like it fights off viruses), I'm not so hopeful here.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2...
(summary: chemotherapy actively kills people, some people would have survived without it)
And the trials registry entry says "No results published": https://clinicaltrials.gov/ct2/show/NCT04261517
Update: I asked the person on twitter and here it is: http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43... Apparently it's in chinese.
Median age for the control group and test group was 24yrs and 18yrs respectively. This isn't the ideal sample group for testing this drug for COVID-19 indication.
But more importantly... Dosing was only 400mg once per day versus recommended 500mg twice per day as performed in the French trial.
Taken together, this trial tells us very little on how this drug would perform at proper dosing on severe subjects in vulnerable age range and/or with prior co-morbidities.
link to the trial on clinicaltrials.gov is here: https://clinicaltrials.gov/ct2/show/NCT04261517
patients in both tx and control arm fared better than in the french study from earlier this week, suggesting patients were healthier / lower risk at baseline
patients got slightly lower dose in this study (400 mg / day) vs the french study (600 mg / day)
http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43...
I think it helps if you can read Chinese, though Google Translate seems to do a pretty ok job on it.
By now everybody should know that the successful dosis is 2x500mg per day for 10 days. Not 1x 400mg per day, which is the old dosis for Malaria prevention. This dosis needs at least 2-3 weeks to be effective (saturate the cell membranes with zinc), and by then the infection is already over. And the Chinese treatment plan contained much more.
A study with zero value.
Amongst doctors both hydroxychloroquine sulfate and chloroquine phosphate run under broadband antiviral.
Is that twitter reply accurate?
https://twitter.com/GaetanBurgio/status/1241201751916568576
https://twitter.com/MicrobiomDigest/status/12414295448478638...
It's basically a "there could potentially be a causal link here; needs way more research" type of study.
Chloroquine has been recommended by Chinese, South Korean and Italian health authorities for the treatment of COVID-19.[47][48] These agencies noted contraindications for people with heart disease or diabetes.[49] Both chloroquine and hydroxychloroquine were shown to inhibit SARS-CoV-2 in vitro, but a further study concluded that hydroxychloroquine was more potent than chloroquine, with a more tolerable safety profile.[50] Preliminary results from a trial suggested that chloroquine is effective and safe in COVID-19 pneumonia, "improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course."[51] Self-medication with chloroquine has caused one known fatality.
If fighting covid means we need new drugs then we look at a long development time that will likely stretch the availability of a therapeutic behind the availability of a vaccine.
Obviously everyone knows that these things are needed NOW, all bureaucratic road blocks are removed save the really important and necessary ones. You cannot just hand out a drug to millions of people or inject them with vaccines without thoroughly testing their safety first.
Imagine if the "cure" to covid was long term harmful in a broad population, e.g. it affects 5% of the people negatively. The health, societal and economic impact could wipe the floor with covid.
Not really, a panacea is a drug that cures everything. If chloroquine was found to be an effective antiviral, it would only be a drug that cured two things. That's common enough to not warrant excessive skepticism taken alone.
Did I just make that up?
I wonder about the antiviral activity, though. What I've read is about possibly faster drop in virus levels. And I suppose that HCQ could be interfering with some stage of intracellular virus production. But time will tell.
The happy dream is maybe hydroxychloroquine has prophylactic tendencies since it is something people can take long term to be at a substantially lower risk vs catching COVID. The abstract doesn't really show much either way on that front.
Spitballing as an amateur, I suspect once someone has actual symptoms or is verging on a serious case it is too late to help - what is a drug supposed to do, regrow a busted lung? It comes to a point where the virus isn't what is killing you, it is the damage the virus did while breeding and/or the immune system overreacting fighting back and going haywire. Antivirals should help but aren't expected to be magic for either of those things.
https://swarajyamag.com/insta/covid-19-india-recommends-hydr...
It's an immune system inhibitor, so this seems like a bad plan.
Not unless the cytokine storm is what ends up killing the patient in the end.
https://www.vox.com/2020/3/12/21176783/coronavirus-covid-19-...
Then it may be a good idea. The immune system is a very complex _system_ so some parts may be active and some parts suppressed at the same time and that may be what’s need for the fastest recovery.