A prospective cohort study from the Dominican Republic finds antibody levels associated with protection against SARS-CoV-2 infection shift upward during periods of high community transmission. The work indicates immune correlates of protection depend on exposure frequency, meaning the same antibody measurement can translate to different risk depending on how much virus is circulating. The study directly affects how clinicians and manufacturers interpret immunologic markers for protection across varying epidemic conditions—an issue that remains central as public health strategies and vaccine schedules evolve.