Covering intake register for a whole house fan in winter

Go ahead and block them off.

My house was built in the same era and has similar vents in the bedrooms. I believe the rationale is the construction of this era had become so tight that infiltration alone was insufficient to provide fresh air into the house, so these vents were installed as intentional infiltration.

In my case, I'm not convinced the construction was all that tight. Even if yours is that tight, you get enough infiltration from the old section that I don't think you will have an issue with stale air if the vents were sealed off with insulation. Even if you do notice the air being stale afterwards, it's easy enough to remove the insulation to regain some infiltration.

If you do find the need for some fresh air, the only energy efficient solution is an air to air heat exchanger that heats incoming air with the residual heat of outgoing air. These units are installed in homes that are truly tightly built. As in refrigerator like tightness. Without these exchangers air in such houses becomes noticeably stale.

Only caution would be if it's actually in the floor, in which case you might want to consider precautions from liquid water going into it. Down low it won't vent moisture as well, but since that's not a concern for you it should not matter much - right behind the toilet bowl would appear to be your ideal intake position. Negative pressure is fine in ducts unless you are using a jet engine rather than an inline vent fan.