I'll explain it as best I understand it. What I know comes from watching Dr. Roger "MedCram" Seuhult, MD of many hats, on youtube, "some guy on youtube" if you will. He helps run a "Khan Academy" of sorts for medical professionals. Students can get professionally accredited brownie points via MedCram. He also oversees an ICU from time to time working, I believe, at a teaching hospital. He commented in one video that learning to use ventilators has basically been his life's work.
Going by Seuhult, there are two known mechanisms by which hydroxycholoroquine might work.
1) It raises the ph of the lysosome created when a virus tries to merge with a cell and infect it (dump its RNA load into the cell). With a higher pH, the merging process does not succeed and infection is blocked. (The merging process occurs after the virus attaches to a cell by latching onto an ACE-2 receptor on the target cell's surface. Attaching to an ace-2 receptor is not enough to infect a cell. It's just the beginning of the process.)
2) Chloroquine could act as an ionophore permitting zinc ions to cross a cell's membrane. Once the zinc is inside it can prevent viral replication if it is in the right place at the right time.
Chloroquine has been used in treating malaria for decades, and hydroxychloroquine is better tolerated than chloroquine. Seuhult was not opposed to managing its side effects.
The idea of using azithromycin was new to Seuhult when he heard of Raolt Didier's first paper. He quite diplomatically said, "That's interesting that azithromycin might have an effect against viruses. It is an interesting point, and one that has to be looked into to see why that is the case." That may be the most polite phrasing of "Reallllly????" I've ever heard, or it might just be him being respectful and hopeful despite his surprise.
Seuhult did say he found azithromycin problematic because of the long Qt side effect. He did not like combining two drugs with the same dangerous side effect.
I would say that Seuhult seems quite pragmatic when it comes to medicine. If it works, then good. His interest in thermal hydrotherapy is an example. He is quite interested in
whatever might overcome the immune-suppressing effects of SARS-CoV-2.
ETA: Saw
a medical school's COVID-19 protocols. Among optional treatment components for ICU patients:
"Azithromycin 500 mg day 1 then 250 mg for 4 days (has immunomodulating properties including downregulating IL-6; in addition Rx of concomitant bacterial pneumonia)"
Down regulating IL-6 would help avoid a cytokine storm? All the people on twitter think they know better, of course.
www.evernote.com
www.theguardian.com
