The innate immune system is key for fighting viral infections, but can go overboard with CRS during severe disease. But dampening it early in an infection is probably not smart. The kinetics of when to take anti-innate-immune therapies in COVID are important to think about. 1/n

As I understand it (h/t @ArtKrieg), HCQ/CQ block innate receptors like TLR7/8/9. Blocking these early during a SARS-CoV2 infection could exacerbate, not help in treating, COVID. Later in disease, during cytokine storms, cooling off immune response may be smart (like anti-IL6) 2/n

Prophylaxis with HCQ/CQ regimens is potentially harmful in light of this - we need an innate response to fight viral infections. Need clinical trials to figure this out as giving them to prevent or early in disease is potentially bad for mounting an immune response. 3/n

What's more troubling is I've heard from several frontline physicians that they are taking HCQ/Azi prophylactically. Might be crazy, but could use of HCQ explain in part hi rate of bad infections among healthcare workers? High viral dose clearly driver, but HCQ making it worse?

And I forgot to add at the beginning... I'm an immunologist!

(true fact, but included for comic levity in this otherwise serious thread)

As follow up, CQ was used in a 2011 trial for viral prophylaxis of influenza infection (another respiratory RNA virus). Didn't work at all. Slight imbalance in numbers against its use (not stat sig), but significantly higher side effects. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70065-2/fulltext