Hospitalizations and deaths, some of the best real-world readouts for virulence, by themselves can be fraught metrics to use, says Müge Çevik, a virologist and infectious-disease expert at the University of St. Andrews, in the U.K. Not all places have the same standards of care, or the same access to treatments. Sick people might be admitted to a hospital because of a nastier form of the virus—or because of risk factors that made them more vulnerable to begin with. Immunity to SARS-CoV-2 has also been building over time, muddling susceptibility further. And much of the hardship caused by the coronavirus remains outside hospital walls. The difficulty of comparing populations may be part of the reason why different studies looking into variant severity have sometimes turned up discordant results. Ballooning case rates also have a way of reinforcing themselves: When many people suddenly get sick—perhaps because a more transmissible variant has emerged—medical infrastructure gets overwhelmed, and more people might die, even if the virus itself is no more harmful. “The epidemiology is so noisy, it’s so hard to say,” Vineet Menachery, a coronavirologist at the University of Texas Medical Branch, told me. (Researchers now generally agree that Alpha is deadlier than other variants; the news on Delta is less certain.) That puts the onus on researchers to meticulously catalog not only the variants infecting us, but the characteristics of the people they most strongly affect, says Rebekah Honce, a virologist at St. Jude Children’s Research Hospital. “It’s a trifecta of host, agent, and environment—you can’t ignore any branch.”