There's a big footnote about the CO2 timing. The drop begins earlier than 1610, which seems right. The model on the social side is somewhat crude. For example, I'd say you don't have to literally kill off 50 million to get the effect -- but a number of things compound the effect, one is simple demographic loss, ie a population that would have been say 40 million in 1600 can't reach that level because 60% of the population died in say 1550 so there just are missing people who otherwise would have been born.
The other is social disruption, which we know for the Americas can mean simply dispersing and doing less agriculture as well as avoiding production for tribute and/or escaping the levels of society that used to level the tribute.
The effect in MesoAmerica of the Europeans was something like the effect of the Mongols on Mesopotamia: massive depopulation, social collapse, destruction of irrigation systems and so on, but on a much greater scale in a region with a much larger potential biomass.