I note I am only seeing this in Twenty Nineteen but it might also be a problem in other themes. I did explore all the "Twenties" and a few others to try and find if it was to do with editor styles. Props to @jasmussen for the idea to explore that.
I see the following in Chrome and Safari:

I tested on branch today with a recent install/run to make sure up to date. I am marking this as high in case this is a situation needs fixing for 5.4 and looping in @mapk and @jorgefilipecosta. I know a few have seen this infrequently before but it now seems constant.
A little note, if it does turn out to be Twenty Nineteen I can make a trac ticket but just in case this is editor let's open here first.
This trac ticket might be related and if so good to get fixed for 5.4: https://core.trac.wordpress.org/ticket/48526
Great detective work.
The misalignment issue you report is almost certainly the one that I have provide a patch for in the trac ticket. We really need that shipped for TwentyNineteen, as the refactor of the editor that makes the misalignment happen will ship with 5.4.
There's a separate misalignment issue with the default appender that needs fixing in the block editor, note the margin on the left here:

And then note once I've started typing:

Note that the font discrepancy is _separete_ from that, and is a TwentyTwenty specific issue, that is in part tracked in https://github.com/WordPress/gutenberg/issues/18571.
Just a heads up that I've updated core.trac.wordpress.org/ticket/48526, and it should definitely take care of this. It needs some testing and a couple more small fixes before landing.
Closing this ticket as https://core.trac.wordpress.org/ticket/48526 seems to address the issue. Thank you to all involved.
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Just a heads up that I've updated core.trac.wordpress.org/ticket/48526, and it should definitely take care of this. It needs some testing and a couple more small fixes before landing.