Thread by @microbeminded2

I see some MDs/scientists dismissing #hydroxychloroquine as a potential treatment for #COVID-19 and that may be short-sighted. That's b/c studies on hydroxycholoroquine thus far haven’t considered a central mechanism of action by which the drug might help patients with COVID-19

2/ As far as I can tell, the main rationale for treating #COVID-19 with #hydroxychloroquine is this: chloroquine (a drug similar to hydroxychloroquine) was shown, in the lab, to be a zinc ionophore:
journals.plos.org/plosone/articl…

3/ A zinc #ionophore is a compound that, in simple terms, creates a channel in the outer membrane of cells that allows #zinc to more easily move from the outside of the cell to the inside (it can help increase levels of intracellular zinc)

4/ If chloroquine (+ potentially hydroxychloroquine) are zinc ionophores, that cld matter for COVID-19 b/c this study found intracellular zinc (Zn2+) inhibited Coronavirus RNA polymerase in the lab (RNA polymerase is an enzyme the virus uses to replicate): journals.plos.org/plospathogens/…

5/ To summarize, taken together, those studies suggest chloroquine (and hydroxychloroquine) should be administered w/ zinc for #COVID-19. Also, MDs familiar with the hydroxycholorquine/zinc combo told me the intervention might be most effective in early-stage COVID-19 disease

6/ That is because inhibiting RNA #virus replication w/ Zn2+ (intracellular zinc) is believed to work better when #viral load is lower (the goal is to prevent spread of the virus). When viral load is very high already (many cells are infected) perhaps the Zn2+ isn’t as effective

7/ It’s also possible that #hydroxychloroquine cld work as a zinc ionophore w/o the need for zinc supplementation. That’s b/c some COVID-19 patients might already have enough zinc in their systems naturally that could enter infected cells. That possibility must be further tested.

8/ Going back to hydroxychloroquine potentially working better in early stage #COVID-19 disease, that may be why this team in #Korea tested its use (without zinc) as a treatment to prevent people exposed to #COVID-19 from getting sick in the first place: sciencedirect.com/science/articl…

9/ The study (in press!) gave hydroxychloroquine to 211 individuals potentially exposed to COVID-19 at a Korean event. They were able to follow up w/ 205 of the individuals, and after 14 days in quarantine (while taking hydoxychloroquine) none tested positive for COVID-19 via PCR

10/ Of course the finding DOES NOT mean hydroxychloroquine was the reason individuals in the Korean study didn’t tested positive for COVID-19. It cld have been luck! But the study does provide some rationale for testing hydroxycholoroquine as a preventative for COVID-19

11/ By the way, the authors of the Korean study discussed above do acknowledge that their study has weaknesses, for example stating that “there was no adequate control group and the study was conducted at a single center.”

Overall the main point of my tweets is 1) we need to design RCTs for #hydroxychloroquine that better consider its potential mechanisms of action 2) We need to better test hydroxycholoroquine (potentially administered w/ #zinc) in early-stage #COVID-19 or in a preventative fashion