National- and state-level SARS-CoV-2 immunity trends from January 2020 to December 2023: a mathematical modeling analysis.

Introduction: Effective immune protection against SARS-CoV-2 infection and severe COVID-19 disease continues to change due to viral evolution and waning immunity. We estimated population-level immunity to SARS-CoV-2 for each of the fifty United States (U.S.) and the District of Columbia from January 2020 through December 2023.

Methods: We updated a model of SARS-CoV-2 infections to align with the latest evidence on SARS-CoV-2 natural history and waning of immunity, and to integrate various data sources available throughout the pandemic. We used this model to produce population estimates of effective protection against SARS-CoV-2 infection and severe COVID-19 disease.

Results: On December 30, 2023, 98.6% of the U.S. population had experienced immunological exposure to SARS-CoV-2 through infection and/or vaccination, with 88.3% (95% credible interval (CrI): 78.4%, 95.5%) having had at least one SARS-CoV-2 infection. Despite this high exposure, the average population-level protection against infection was 31.6% (25.1%, 41.2%). Population-level protection against severe disease was 66.1% (59.2%, 74.3%).

Discussion: A new wave of SARS-CoV-2 infections and COVID-19-associated hospitalizations began near the end of 2023, with the introduction of the JN.1 variant. This upturn suggests that the U.S. population remains at risk of SARS-CoV-2 infection and severe COVID-19 disease despite the high level of cumulative exposure in the United States. This decline in effective protection is likely due to both waning and continued viral evolution.