Thread by @sciencescanner

I agree. Complement misregulation is key to understanding #covid19 symptomatic variations

https://twitter.com/cgfran01/status/1250117112535887874

This chimes with our work at #MethuselahHealth - where we have uncovered complement regulation as a key player in ageing. Around 50yo we see significant “innate autoimmunity” as proteome errors accumulate and trigger self-recognition

This in turn results in a suppression of complement to prevent “self-immolation”, so reducing protection against infections. But these changes in complement balance also mean that when rampant infection does occur the amount of collateral damage is much greater in the elderly

Fits exactly with the age profile of vulnerability to severe, life-threatening symptoms from #COVID19. It’s not just about co-morbities - being old by itself causes greater harm from complement over-activation in response to viraemia

Harder question is what, if anything, we can do therapeutically... blocking complement will harm ability to control virus prior to adaptive immune response. But blocking complement, for example with danicopan, may be beneficial once IgM positive

Or alternatively use the allostetic Compkement Factor D inhibitors #MethuselahHealth is developing - block excess complement activation without inhibiting the normal response

Unfortunately these preclinical candidates won’t be helping anyone in this pandemic! Maybe next time...