I never implied that it's been proven that the drugs do NOT work. If I haven't made it clear here, I made it clear on Debate Politics in the long thread about HCQ being given to New Yorkers. I posted several times there to say that while efficacy hasn't been proven, lack thereof hasn't been proven, either.
Yes, smaller pilot studies, in-vitro activities, are, in terms of hierarchy of evidence, at best hypothesis generation studies (something I said over and over on DP, too). And they are good and important; otherwise we wouldn't have found many medicines that do work. But that's their only role: hypothesis generation. Then the hypothesis needs to be put to the test.
The existing studies, it is not that they have the wrong hypothesis. They are asking legitimate questions: does HCQ work for advanced cases of COVID-19? So far, the data on this is discouraging although like you said definitive proof isn't in yet; there's been case-control series, retrospective studies, small non-randomized studies, and even a couple of small randomized controlled trials (from China, one that suggested it works, one that suggested it doesn't). Large randomized controlled double-blind trials are underway (including for prophylaxis) but haven't concluded yet. Given that in the case of double-blind RCTs, only at the end one opens the envelopes to see who got the active drug and who got placebo, the conclusions are not in, yet.
My guess, from reading a number of studies, some better than others, some very flawed, some relatively decent, is that HCQ will not pay off. But it's just a guess. Proof will come when it comes.
Even cultured human cells can't match the real life situation of a live organism infected with an aggressive virus (for example, cultured human cells don't produce cytokine storms; are not subject to disseminated intravascular coagulation, are not subject to the full dimension of the host's immune response with its advantages and disadvantages). Also, the virus can't be sequestered in some organs and multiply too fast before the drug can stop them. Often the concentration of in-vitro inhibition can't be achieved in-vivo with regular, non-toxic doses.
A drug can show beautiful inhibition of replication in cultured cells... and then once the virus infects a live organism, it may rapidly overwhelm that organism in a way that makes the drug useless.
Again, in-vitro and in-vivo are not just different... they are VASTLY different. Again, in-vivo activity is neat to generate hypothesis, but proves NOTHING in terms of clinical efficacy and safety.
Billions of human doses: not for COVID-19. Safety is disease-specific, a point I made over and over but you come back to the idea that people with lupus, malaria, and RA have taken billions of those doses. Sure, neat. However, those people didn't have COVID-19 which didn't even exist when they were taking those billions of doses. Different ball game.
OK, is HCQ a huge poison that makes most patients taking it drop dead? No. The billions of doses used to treat malaria, lupus, and RA have already demonstrated that. But is it safe in humans for use in cases of COVID-19? We don't know yet, but the first few pieces of info we have are not encouraging.
I don't have a dog in this fight either. I hope HCQ works, I hope zinc works, I hope remdesivir works, I hope something else does.
But it hasn't been proven that any of these do work; it hasn't been proven that they don't, and it hasn't been proven if they may or may not help different degrees of patient severity; it hasn't been proven if they are good prophylactic drugs for SARS-CoV-2.
Look, about the in-vitro versus in-vivo: we don't need to go far. Remdesivir showed in-vitro activity against viruses of the Filoviridae family (Ebola). That generated the hypothesis that it might work against Ebola, in vivo. Well, so much for that. It was an utter failure in the real-life treatment of patients infected with Ebola. It's being repurposed now for COVID-19. We'll see.
