Isolated populations are all going to be creating isolated variants of any disease doing well enough to stick around.

And the impact of events where any individuals die to a new variant, is amplified for a small population. The risks of highly correlated vulnerabilities are on top of that.

Variants of the flu continue to quietly emerge and kill people today. Despite all our regular exposures to their constant churn and weather shielded environments.

But you are certainly right that the cross-overs are incomparably worse. And diversity becomes species extinction protection at that level.

> The risks of highly correlated vulnerabilities are on top of that.

For small groups, it doesn't matter too much if it's correlated or not. A 'small' hit doesn't exist, so 20% or 80% is a wipe-out either way. You don't have big population dynamics, you can't take even a 20% hit to your population as a small group. Even if you'd have the genetic diversity of modern humans, your population would still be damned (my 2-3 females gone example, it's an extinction vortex [0])

> Variants of the flu continue to quietly emerge and kill people today. Despite all our regular exposures to their constant churn and weather shielded environments.

Flu is specifically adapted to exactly what you point out. Check out virulence in doors vs out doors for influenza. Also, it's precisely regular exposures that allows influenza to persist, as it has a rapid mutation rate, and it benefits from as much exposure to humans as well. There is no evidence for Flu before the Neolithic, precisely because the flu is adapted to constant exposure to an inter-connected population, requiring a critical community size in the hundreds of thousands.

[0] https://royalsocietypublishing.org/rspb/article/290/2011/202...