BACKGROUND: Amid changing variant and immunity landscapes since early in the coronavirus disease 2019 (COVID-19) pandemic, common COVID-19 symptoms need better understanding in relation to prior immunity or infecting variant. METHODS: American Red Cross blood donors were surveyed during February-April 2022 about prior COVID-19 vaccinations and symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Donations were tested for anti-nucleocapsid antibodies to inform infection history. Restricting analysis to donors with survey-reported infections during the Omicron BA.1-predominant period (19 December 2021 through 19 March 2022), we used multivariable logistic regression to compare symptoms by existing immunity from prior infection or vaccination. Restricting analysis to those with no existing immunity, we compared symptoms by variant-predominant period of their first reported infection (BA.1 vs before). RESULTS: Among 9505 donors with a BA.1-predominant period infection, donors with prior infection (n = 1115), vaccination (n = 5888), or both (n = 1738) were less likely than those without prior immunity (n = 764) to report loss of taste or smell, lower respiratory tract, constitutional, or gastrointestinal symptoms and more likely to report upper respiratory tract symptoms. Stronger associations followed recent prior infection, vaccination, or more vaccine doses. Among 8539 donors without prior immunity, those with survey-reported infections during the BA.1-predominant period (n = 764) were less likely to report loss of taste or smell, or lower respiratory tract symptoms than those with infections before this period (n = 7775). CONCLUSIONS: Our data suggest that both prior immunity and Omicron predominance redistributed COVID-19 symptoms toward upper respiratory tract presentations and likely both contributed to a decrease in COVID-19 severity over time. These findings may better inform COVID-19 identification in high-immunity settings and demonstrate additional benefits of vaccination.