Most people have had one or more colds due to seasonal coronaviruses (CoV) with the number of prior infections increasing with age. SARS-CoV-2 entered the human population in late 2019, causing the COVID-19 pandemic. Before that no one had immunity yet older males are at higher risk of severe COVID-19 illness. One explanation is that prior antibodies to seasonal CoVs may enhance SARS-CoV-2 risk through a process called antibody dependent enhancement. To assess that hypothesis we first need to know if seasonal CoV antibodies interact with SARS-CoV-2, how common those antibodies are, and if older men have more of them. We will develop a pan-CoV assay to compare prevalence of all human CoVs by age and sex. Findings will inform SARS-CoV-2 sero-surveys, severity profiles and vaccine strategies.