[ComputerGuru]

I don’t see how any of this is coming as a surprise to anyone, or even why people are bothering (questionable science behind the choloroquine paper aside, even).

This is a comment I posted to HN three weeks ago, when I was pretty sure (but unfortunately wrong!) that the suggested chloroquine dosage for purportedly treating covid-19 was being reported in the wrong units because it was so high, using only the information in the FDA docs on the chloroquines: https://news.ycombinator.com/item?id=22611041

Choloroquine is very well known to have an extremely low therapeutic index (ratio of fatal dosage to effective dosage) and people (well, non-infant children) have been known to die from just a 1g dose. The recommendation for Covid-19 starts at an order of magnitude higher than the recommended FDA dosage for malarial suppression.

(Pretty much) everything can kill viruses at high enough doses. The question is if it can do it without killing the patient as well, and it is eminently clear from existing, solid research that choloroquine doesn’t fit that bill.

Hydroxychloroquine is better tolerated than chloroquine base, but not that much more to sufficiently matter. It also has its own horrible dangers (including complete blindness from accelerated macular degeneration) that have been well documented at long-term “low” dosages; it is not a stretch to assume they would happen with short term high dosages.

There is a reason these only work in vitro - you don’t have to worry about killing the patient there.

[GekkePrutser]

Ouch... Nasty stuff. I had no idea. Thanks for explaining all this in plain English because that paper is Chinese to me :)

[cameldrv]

The half lives of these medications are very long, 30+ days I believe. This makes a large dose for a short number of days more reasonable than at first glance.

[ComputerGuru]

But the recommendation is for a high dose once or twice a day for a week +, which can easily add up.

[the8472]

https://xkcd.com/1217/

[nwienert]

“Only work in vitro” and the fact it’s actively used around the world in vivo contradict.

Also can you cite the solid research showing hydroxychloroquine + arithromycin failing for covid-19?

[ComputerGuru]

I mean specifically with regards to treating covid-19, not for other purposes. Sorry if that wasn’t clear. I didn’t say there’s a study that says hydroxychloroquine combined with arithromycin is an ineffective combination, but that unless there’s a scientific reason to assume something will increase the effectiveness of such a possibly lethal drug without exacerbating its negative side effects then there is no reason to start with the assumption that it is safe.

Keep in mind that the lack of rigor in the current pre-peer review literature coming out means that you have to take everything into account and with a grain of salt. For example, a drug showing effectiveness might have been with a mild case that started with a low viral load and wouldn’t have progressed any way (this is just an example, I’m not saying that is the case). Since the therapeutic index is so low, you can’t just dial up the dosage to treat severe cases that actually require pharmaceutical intervention, because it’s a non-starter.

[nwienert]

Can you cite it not working for covid-19 in vivo? From what I've found there are early stage trials showing success, plus a few larger anecdotal populations showing bigger success, but nothing that scientifically definitively concludes either way.

[ComputerGuru]

Yes, there simply hasn’t been enough time for proper studies to have been made one way or the other [0]. The only “study” showing in vivo efficacy is pretty much a bunch of bunk and has huge issues. It did not report on actual treatment outcomes but only on nasal swab results without a control arm, never mind that covid-19 has been demonstrated to move from upper respiratory down into the lungs in most cases that progress to pneumonia or respiratory distress anyway (so a nasal swab says nothing and can come back negative while the patient is dying of respiratory failure).

[0]: https://www.cebm.net/covid-19/chloroquine-and-hydroxychloroq...

[nwienert]

That means your claim that it “only works in vitro” is false, though. The right claim would be “we don’t know yet”.

Also you do a lot of work to make it sound like a foregone conclusion it doesn’t work (appeals to authority in “anyone paying attention”).

The problem is there is now a lot of anecdotal evidence of it working from good sources (teams of doctors on frontlines from around the world). So really you can’t appeal to anyone paying attention.

[ComputerGuru]

Yes, so far as we know.