Litestream runs continuously on a test server with generated load and streams backups to S3. It uses physical replication so it'll actually restore the data from S3 periodically and compare the checksum byte-for-byte with the current database.
I made sure Litestream would be safe with the primary database so it only communicates through the SQLite API for locking and state. It should be completely safe to run unless there is a bug in SQLite itself. You can also continue to use a separate periodic backup strategy if you're not comfortable running Litestream alone for disaster recovery.