ls -la /etc/ssl/certs ?
did you also run update-ca-certificates -f ?
# ls /etc/ssl/certs/ISRG_Root_X1.pem
did both, result is same
# openssl verify /etc/letsencrypt/live/mydomain.com/cert.pem
C = US, O = Internet Security Research Group, CN = ISRG Root X1
error 2 at 2 depth lookup: unable to get issuer certificate
error /etc/letsencrypt/live/mydomain.com/cert.pem: verification failed