An alternate subtitle for this book might have been "A Bunch of Stuff Niall Ferguson Felt Like Writing About". It's very wide ranging. But the theme is right up there on the book flap in big type: "All disasters are at some level man-made." One chilling comparison:
Politics explained why World War II killed twenty-five times as many Germans as Americans. Politics explains why COVID-19 has thus far killed eighteen times as many Americans as Germans
There's a lot of (what I'd call) "theoretical history", where he attempts to tease out laws (or at least widely-applicable lessons) from worldwide events spanning millennia. (E.g., How often are empires born, and how long do they last? Even more relevant to present-day: how often do devastating plagues occur?) There's discussion of probability distributions. (E.g., Are catastrophes better described by a normal, Poisson, or power-law distribution?) And networks are relied upon for their explanatory power. (E.g., and very relevantly, how do viruses spread from one region to another?)
But there's quite a bit of normal history too, and it's centered around the book's title, Doom. Plagues and epidemics, primarily, since they're on everyone's mind. But other natural and unnatural disasters are discussed: Chernobyl, the space shuttle Challenger, earthquakes, volcanoes, wars, famine, …
There's also speculation on foreign policy, and (in conclusion) an overview of various science fiction predicted futures; which is likely to be most accurate? (Unfortunately, it's not The Moon is a Harsh Mistress.)
Ferguson finished the book in August 2020, more or less in the middle of the COVID-19 pandemic. (More accurately, as I type, I hope it was the middle.) That was pre-Moderna, also pre-variant. His takes on various failures in various countries are slightly heterodox, not totally wacky. Also, unfortunately, not very interesting, if you've seen dozens of analyses and commentaries on the same theme over the last couple years.