The 'varnish mailbox lag' icinga alerts as implemented in the parent task have been going CRITICAL for a while and in some cases result in 503s spikes until a manual varnish-backend-restart is issued on the affected machine.
I'm opening a more-specific task than T145661: varnish backends start returning 503s after ~6 days uptime to investigate whether there's more we can do to mitigate the recurring mailbox problem, not the general upload 500s problem and file backend of which AFAIU mailbox lag could be just a symptom and not the root cause.