The Two-handed property definition on pg. 147 (after errata 1.0) has the easy answer:
This property is only relevant when you attack with the weapon, not when you simply hold it.
If you aren't using your two-handed weapon for the OA, you can just make an unarmed punch with one of your hands.
Given the wording of Opportunity Attacks on pg. 195:
...you use your reaction to one melee attack against the provoking
and the wording of unarmed strike:
Instead of using a weapon to make a melee weapon attack, you can use
an unarmed strike: a punch, kick, head-butt, or similar forceful
blow (None of which count as weapons).
there isn't anything preventing you from making an unarmed strike while holding your weapon, even if both hands were full.