The astronauts aren't using the GSA city pairs program and the Fly America act does not apply to space travel. Totally separate issues.

As for Fly America Act, yes, in theory one would have to pay the higher US airline price, but that rarely is the case because of the contract fares.

BTW, the rule is only that it be a US carrier flight, not metal, so codeshares are okay, and it applies only on flights to/from US.

Having done government travel, it's rarely a real burden, especially because traveling business class on the government's expense is extremely rare, and that's when foreign flag carriers have a leg up.