Hi Patrick,
Have you figured this out?
We just started experiencing the 500 error on Chrome Version 102.0.5005.63 (the latest one). We have Portal for ArcGIS site and we provide PDF files on this site. PDF files are a part of the Portal content. Some users get the 500 error and some don't.
After looking at the web logs I found the following:
When the PDF file is requested there is status is 200 (you can see the browser spinning trying to get the content), then immediately the log shows status 401 for the same file, and then error 500.
PDF files are shared with everyone.
Clearing the browser's cache and cookies do not resolve the issue.
There are no issues on Edge or IE.
I don't seem to have this issue with services published to the host server.