to make long story short IMO - you can't use Yubikey directly as a additional factor in GP.
You'll need to have external service to integrate with and use it as an idP (identity Provider). There you can setup Yubikey as an additional Auth factor.
I have been working on YubiKeys and GP, we were not really looking for a MFA solution for GP but it would appear that we have one, and it's quite cool. Albeit we do have another issue with a Windows Security Cert pop-up, which does not really create an issue but is an additional step we would like to remove. My guess it that when the GP agent authenticates it sees the user cert and want's to know if it should be used. I am looking for work arounds for this, any ideas?
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