Thread by @lpachter

From the outset of the #covid19 pandemic, it's been clear that risk of death increases sharply with age. But why? The intuitive hypothesis is that ACE2 expr. increases w/ age, but early in April, @sinabooeshaghi and I showed the opposite is true in mice. biorxiv.org/content/10.110…

Now, in a paper from the labs of @tuuliel and Christenson, @silvakasela et al. have performed a careful analysis in human, and they find the same.

https://twitter.com/tuuliel/status/1312824818237136898

BTW we saw the same patterns for ACE2 expression with sex in mice, namely males had *lower* levels of ACE2, and @silvakasela et al. find the same in humans despite the risk of death being much *higher* for males.

A person's age is the strongest predictor of their risk of death from #covid19, yet despite a lot of work the past 6 months, the reason why remains a mystery. There are lots of hypotheses floating about but I have not seen a convincing explanation.
nature.com/articles/d4158…

Specifically, there does not appear to be a single threshold age where risk suddenly increases. There is a continuum of (super-linear) higher risk with age. In my mind explaining this is a key research question, and I'd be curious to hear if anyone knows of credible work on this.

Linking to this thread which already branched off an earlier tweet:

https://twitter.com/LindorffLarsen/status/1312852135596437505?s=20