There were indeed consistent failures to specific IPv6 endpoints, clearly identifiable through curl, while all the IPv4 endpoints were ok.

This happened with pypi (IPv6 BGP routing problem caused by a bad route from one of our peers combined with their fastly CDN not reply to us on IPv6 from the other side of the ocean for some weird reason), but also with yum and apt mirrors (seemingly random problems with the IPv6 service or firewall of the remote endpoint), and various other web resources accessed from pipelines.

The solution always was to temporarily block the bad IPv6 endpoint(s) or temporarily completely disabling IPv6 on the server itself or on the squid proxy server for workloads without direct connectivity.

Obviously it also can be the other way around, but in practice it appears to happen less often with IPv4, and if it does things get addressed quickly instead of taking hours or days or weeks.