Changes in population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States between December 2021 and November 2022

IMPORTANCE: While a substantial fraction of the US population was infected with SARS-CoV-2 during December 2021 – February 2022, the subsequent evolution of population immunity against SARS-CoV-2 Omicron variants reflects the competing influences of waning protection over time and acquisition or restoration of immunity through additional infections and vaccinations. OBJECTIVE: To estimate changes in population immunity against infection and severe disease due to circulating SARS-CoV-2 Omicron variants in the United States from December 2021 to November 2022, and to quantify the protection against a potential 2022–2023 winter SARS-CoV-2 wave. DESIGN, SETTING, PARTICIPANTS: Bayesian evidence synthesis of reported COVID-19 data (diagnoses, hospitalizations), vaccinations, and waning patterns for vaccine- and infection-acquired immunity, using a mathematical model of COVID-19 natural history. MAIN OUTCOMES AND MEASURES: Population immunity against infection and severe disease from SARS-CoV-2 Omicron variants in the United States, by location (national, state, county) and week. RESULTS: By November 9, 2022, 94% (95% CrI, 79%–99%) of the US population were estimated to have been infected by SARS-CoV-2 at least once. Combined with vaccination, 97% (95%–99%) were estimated to have some prior immunological exposure to SARS-CoV-2. Between December 1, 2021 and November 9, 2022, protection against a new Omicron infection rose from 22% (21%–23%) to 63% (51%–75%) nationally, and protection against an Omicron infection leading to severe disease increased from 61% (59%–64%) to 89% (83%–92%). Increasing first booster uptake to 55% in all states (current US coverage: 34%) and second booster uptake to 22% (current US coverage: 11%) would increase protection against infection by 4.5 percentage points (2.4–7.2) and protection against severe disease by 1.1 percentage points (1.0–1.5). CONCLUSIONS AND RELEVANCE: Effective protection against SARS-CoV-2 infection and severe disease in November 2022 was substantially higher than in December 2021. Despite this high level of protection, a more transmissible or immune evading (sub)variant, changes in behavior, or ongoing waning of immunity could lead to a new SARS-CoV-2 wave.