It’s because of breakthroughs—and how few of them we’re finding—that we know that the vaccines are performing well in a broad range of people, knocking back both disease and infection, even as the number of coronavirus variants carrying antibody-dodging mutations continues to rise. By the end of April, when more than 100 million Americans had finished their shots, the CDC had received documentation of 10,262 post-vaccination infections of all severities, according to a report published this week. (That’s a definite undercount of the true number, but breakthroughs are still a tiny fraction of the millions of SARS-CoV-2 infections that have been reported to the agency since the vaccine rollout began.) Breakthroughs could also eventually clue researchers in to how well the vaccines thwart very rare or late-appearing consequences of infection, including long COVID. And the future of COVID-19 booster shots hinges on carefully archiving breakthroughs. Clusters of these post-vaccination infections compelled public-health officials to alter the dosing schedules for measles and chicken-pox vaccines, for example. A subset of the test samples collected from breakthrough cases can also be sequenced, as part of the search for unusual mutations in a pathogen’s genome. Genetic surveillance has, for months, been the pandemic’s bellwether for variants; more than 1.6 million SARS-CoV-2 genomes from around the world have been cataloged in an ever-growing database. Of those 10,000 breakthrough cases, 555—roughly 5 percent—came with sequencing data. Although that’s not a highly representative sample, dozens of those sequences turned up as coronavirus variants that can bypass certain immune defenders. Across the country, the news on variants and vaccines seems mixed, experts told me. One recent study, out of Washington State, found that variants—including several known to stump certain antibodies in the lab—were dominating sequenced breakthroughs. But in Minnesota, post-vaccination infections “just reflect what’s circulating in the community,” Stephanie Meyer, the COVID-19 Epidemiology and Data Unit Supervisor at the Minnesota Department of Health, told me.