That is why I have those for keys I rarely use, such as 'esc' and 'del'. Relatively rare - as they are obviously used frequently enough but not really when typing.

And then I hit them with my middle finger instead, or rather smash them as it requires the whole hand to move slightly.

So in my case does not affect speed or comfort (not a frequent VIM user etc)

But if I only had two thumb buttons I would be ok.