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 October 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 10, 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 10, 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 October 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.

VEP has received reimbursement from Merck and Pfizer for travel expenses to Scientific Input Engagements unrelated to the topic of this manuscript. All other authors have declared that no competing interest exist.

VEP reports grants from National Institute of Allergy and Infectious Diseases R01 AI137093 TC reports grants from National Institute of Allergy and Infectious Diseases R01 AI112438 NAM reports grants from National Institute of Allergy and Infectious Diseases R01 AI146555-01A1 JAS reports funding from the Centers for Disease Control and Prevention though the Council of State and Territorial Epidemiologists (NU38OT000297-02) and the National Institute on Drug Abuse (3R37DA01561217S1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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All data used in the main analysis are available from The Covid Tracking Project, Johns Hopkins CSSE, CDC, Healthdata.gov, US Census Bureau, Ipsos and a JAMA publication.