Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a vital issue for global society. Determining the quality and duration of that immunity is therefore key. But the adaptive immune system is complex, and these factors may differ between natural immunity (obtained by infection) and vaccine-generated immunity (1). Additionally, there is the question of the combination: What kind of immunity develops in people with natural immunity who are subsequently vaccinated? Such “hybrid immunity” is particularly interesting because of the notable finding that people with previous SARS-CoV-2 infection mount unusually potent immune responses to COVID-19 vaccines (2). This is exemplified in two studies in this issue on pages 1413 and 1418 by Stamatatos et al. (3) and Reynolds et al. (4), respectively, which also highlight natural and vaccine-induced immune responses to variants.