Thread by @breastoncdoc

Thread on the #hydroxychloroquine study for Dr. Topol:

(1/8) Assume for a minute that what is going on is that the virus is hijacking autophagy pathways in cells to live and to thrive. We can discuss the support for this hypothesis at length but look at the @NEJM yesterday.

https://twitter.com/EricTopol/status/1263811764287725574

(2/8) The genes expressed in COVID-19 lung are in a large part related to autophagy (nejm.org/doi/pdf/10.105…), and increased neovascularization is a sign of autophagy.

(3/8) Everything in the study reported in the Lancet can likely modulate autophagy in the pneumocyte (ACE inhibition, statins), and famotidine can do so as well.

Were these controlled for?

(4/8) HCQ and CQ are the only FDA-approved autophagy inhibitors.

Were subjects in the Lancet study stratified by LDH level? It seems to predict for severity. nature.com/articles/s4225…

(5/8) We still don't know if #HCQ works from randomized trials. We give it extensively to pregnant women (pubmed.ncbi.nlm.nih.gov/14613284/ & ncbi.nlm.nih.gov/pmc/articles/P…) and it's been used in lupus with few complications for 70 years, so my guess is that any true harm is limited at best.

(6/8) I am also a bit surprised that while cardiac arrhythmias were mentioned in the @Lancet article, QT measurements were not.

Does that concern you?

(7/8) Another possible explanation of the Lancet harm result is observational bias despite extensive attempts to control for it.

Controlling for LDH levels and FiO2 levels (not O2 sats) could have helped us understand this bias if it happened.

(8/8) I know this issue has become extremely politicized.

We all need take a deep breath and try to look at the possible science behind what is going on, so we do not make an enormous mistake.