COVID19 update, September 26, 2020: updates from readers edition

[I am blessed to have a number of readers who scour the primary and secondary biomedical literature for interesting articles and tip me off to them. Many thanks, much appreciated.]
(1) (Hat tip: Jeff Duntemann) A Spanish study appears to show a statistical link between zinc deficiency and mortality among COVID19 hospital patients.

Also via Jeff Duntemann: two blog posts (here and here) about a zinc ionophore that appears to be more effective as such than hydroxychloroquine and — get this — is a component of a hot beverage already consumed daily by hundreds of millions of people in East Asia: green tea.

Taking Clioquinol (CQ) as the standard, as is its the most potent ionophore we have tested in our liposomal assay, and assigning a 100% value to the clioquinol ionophoric activity , then pyrithione (PYR), which is not a polyphenol, displays also almost a 100% activity relative to clioquinol, whereas epigallocatechin gallate (EGCG) has 60% activity and quercetin (QCT) has only 30% the efficiency of clioquinol, on a equimolar basis.Nonetheless, this is a proof of concept assay, and exact ionophoric capacity of each compound will vary with the absolute and relative concentrations of the ionophore and of zinc; it will also depend on temperature, pH of the solution and lipid composition of the liposome (absolute and relative amounts of lecithin, other phospholipids, cholesterol, etc). It will also vary dependent on the fluorochrome used to detect zinc in the interior of the liposome (FluoZinc, Zinquin, etc) and on the concentration of the fluorochrome within the liposome, since different fluorochromes display different strengths to separate zinc from the polyphenol zinc complex.

In any case, in the exact standardized conditions used in our assay, we can conclude the relative ionophoric effect of the different compounds tested.It is, I think, important to remark that the liposomal assay allows to elaborate a scale or a standard of ionophoric strength or ionophoric capacity or potential; and that, once established through this assay that a compound behaves as an ionophore in a liposome, we can say that it will also be ionophoric in any type of cell, as this effect is independent of content of protein, glycoprotein, glycolipids, of the cell membrane, although of course it will vary according to the fluidity of the cell membrane, that depends on its exact lipid composition.

The interviewer asked Dr. Larrea how well zinc is absorbed by cells in the absence of an ionophore.  His answer:

Zinc, 10 micromolar (Zn10), alone, by itself, renders just circa 2% fluorescence of that obtained with CQ. Control means, fluorescence of liposomes without the addition of any substance. That means that zinc alone, by itself is not able to enter the liposomes, as expected. This 1-2% is the background fluorescence of the whole system.

Structural formula of epigallocatechin gallate
epigallocatechin gallate (EGCG)

Bioavailability of EGCG from oral ingestion (read: drinking green tea) appears to be somewhat problematic though. Then again, this is definitely in the category of “can’t hurt even if it won’t help”.

(2) In my inbox I found an older message by “Yves not-Cohen” mentioning a review article in a cardiology journal, “QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review” by Lior Jankelson et al., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211688/

Note that these doctors are not saying: “ZOMG! This drug is poison and teh debbil!” but, rather more prudently:

 [… from] data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in 2 COVID-19 patients from a group of 28 treated with high-dose chloroquine. Limitations of these results are unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT-interval prolongation and potentially increase the risk of arrhythmia. Daily electrocardiographic monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.

Torsades de pointes“, BTW, reads like a ballet term, but is the term a French cardiologist first used in 1966 for a specific types of cardiac arrhytmia, and has since become the standard term (“twisting of peaks”, literally). “Torsades occurs as both an inherited (linked to at least 17 genes)[3] and as an acquired form caused most often by drugs and/or electrolyte disorders that cause excessive lengthening of the QT interval.[4]

(3) (Hat tip: Wayne B.) Florida doctors claim to have found a “cocktail” drug regimen that has a 96.4% survival rate among hospitalized patients.

ICAM isn’t a new drug, it’s an acronym for a combination of existing medications used simultaneously on patients. It uses Immunosupport drugs (Vitamin C and Zinc), Corticosteroids against inflammation, Anticoagulants against blood clots, and Macrolides to help fight infection.

As discussed here previously, multiple studies (including the English RECOVERY trial) have already come out in support of corticosteroids like dexamethasone, and there is enough evidence for blood clotting that a number of places are already applying anticoagulants. Vitamin C and zinc seems sensible as immune system boosters — though I would have added vitamin D or its first metabolite to the cocktail. Finally, macrolide antibiotics like azithromycin probably are more effective in preventing secondary bacterial pneumonia than in combating the viral infection.

To my Jewish readers, gmar chatima tova and have an easy fast if you observe one for Yom Kippur.

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