re: NY HCQ study is a joke. We are being lied to

So how would you approach non-critical patients?

Without evidence base, I am going with HCQ/Azith/Zinc initially for those with LDH, ferritin, d-dimer, and CRP within normal limits. Remdesivir for those with S/S trending downward or no improvement on day 4.

With 40 vials we can treat approximately 7 patients.

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HCQ/Azith/Zinc

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everyone who walks in the door with covid symptoms starting in the last 7 days and not on QT prolonging home meds

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Remdesivir

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everyone who has covid symptoms in the last 7 days and is in a mortality-risk group >10% (age, comorbidities)

anything else wastes drug IMO. I don't think they'll let us use remdesivir like that but that's how it should be used.

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LDH, ferritin, d-dimer, and CRP within normal limits

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I use these to guide cytokine storm. you've probably long passed the threshold for antiviral utility if these are all significantly elevated and need to be pulling the trigger on Actemra

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The doctors having over 90% success rates with HCQ are combining it with azythromycin and zinc salts (Zn+ ion). The antibodies to fight secondary infection so the immune system can focus on CV and zinc salts because most patients have insufficient zinc ion in their blood due to poor diets. The HCQ seems to help the zinc penetrate the epithelial cell walls more efficiently than without HCQ. Once in the cytoplasm the zinc ion can do it's work against RNA polymerase and halt CV RNA replication.

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This is really, really bad science.

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It works. Doctors that prescribe it say so.

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Anecdotally I’ve had no real success with it, and most reputable academic medical centers are phasing it out of their treatment algorithms as the body of evidence simply doesn’t support its use at any stage of the disease. I’m involved in helping with our institutional guidelines and have personally reviewed nearly every meaning HCQ study from around the world over the last 2 months and there’s just not much there. I do agree with the OP that the study in question has flaws and there are better studies on this, but those studies are not encouraging either.

Remdesivir and the IL-6 inhibitors appear encouraging however. I’ve been impressed by how quickly many of my very ill patient have rapidly turned the corner with tociluzimab or sarilumab.

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Anecdotally I’ve had no real success with it

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Anecdotally, we have.

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most reputable academic medical centers are phasing it out of their treatment algorithms as the body of evidence simply doesn’t support its use at any stage of the disease.

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Which ones? Also on no data to support in any stage:

Chen et al. Yale via medRxiv

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Remdesivir appear encouraging however.

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Please share your evidence to support. Also do you use the criteria:
"it appears encouraging", when making decisions while helping determine institutional guidelines.

It's important to note that this was an OBSERVATIONAL STUDY. That is, there was no prescription of who to treat with what therapy, it is only a reporting of baseline characteristics, treatment given and outcome. The significant difference in baseline severity is more a sign of who physicians are considering for treatment with HCQ, not a failure of the trial design.

"Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed."

I spoke to a doc at UMC in NOLA over the weekend on the front lines . The reason why Louisiana had such a precipitous drop over the last 3 weeks or so was because the docs said frick it and started using Hydroxychloroquine on the patients. He said guys like Fauci were none too happy about it. He said the data is out there but CDC, etc want it buried.

One caveat, if the patient was in extremis it had minimal effect meaning if the patient was in the ICU, intubated and had multiple comorbidities the efficacy was limited. Said the virus is like malaria/ yellow fever in a lot of ways.

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This is really, really bad science.

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Let me explain why you are wrong:

First hydroxychloroquine is a safer alternative to chloroquine. Structrually they are very similar except hydroxychloroquine has an alcohol group where chloroquine has a methal group. This makes hydroxychloroquine more water soluble thus allowing a higher rate of metabolism and less bio accumulation.



Both hydroxychloroquine and chloroquine are zinc-ionophores. Chloroquine Is a Zinc Ionophore. Hydroxychloroquine acts as an ionophore the same way as chloroquine.

Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture.

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Increasing the intracellular Zn(2+) concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn(2+) and PT at low concentrations (2 µM Zn(2+) and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC).

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I understand this research was done in vitro however it does proved the concept of zinc-ionophores.

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Also on no data to support in any stage:

Chen et al. Yale via medRxiv

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The relatively young age of their cohort, small cohort size (especially for evaluating a condition with low overall mortality) and lack of cohort background data make this study of extremely limited clinical utility. Useless is probably too harsh a word, but it’s definitely a once over and move on read.

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Please share your evidence to support

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It’s the only drug that thus far has reasonably well designed, well powered RCT data that shows any clinically useful utility. The preliminary data from large IL-6 trials include including the ones at our institution show a pretty significant benefit in severely ill patients.

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Also do you use the criteria:
"it appears encouraging", when making decisions while helping determine institutional guidelines.

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This disease continues to be a moving target and we are all learning on the fly. There are no COVID19 experts yet.