Individuals infected with SARS-CoV-2 mount an antibody response that may vary depending on the severity of the disease. Grzelak et al. assessed the amounts of anti–SARS-CoV-2 antibodies in serum samples from 491 healthy individuals before the pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. The authors developed and compared the performance of four different serological assays measuring antibody amounts and their neutralizing activity. The assays enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in asymptomatic, mildly symptomatic, and severe cases of COVID-19.