The most compelling suggestion I've heard (and heard people who know more than me parrot, mostly from Guns, Germs and Steel) is that EurAfricAsians had domesticated and were living closely with animals of varied backgrounds, where the Americas had very few animals suitable for domestication. The close proximity to other species allowed diseases to pass back and forth; those diseases became endemic in the population, leading to higher rates of immunity to the diseases. I've even seen it argued that overall European/Asian/African immune systems were stronger overall due to exposure to these diseases.

Additionally, the long east-west band of temperate climates across Europe, Asia, and Africa accommodated trade and travel, where the varied north/south orientation of North and South America (especially the relatively impassable central isthmus) impeded trade. This allowed crops, animals, and diseases to all spread quickly in one and poorly in the other, exposing entire populations to diseases much earlier.

Let's not forget that Europe, Asia, and Africa have all had major die-offs in history when new diseases were introduced. They just all got introduced to the Americas at once.