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National- and State-level SARS-CoV-2 Immunity Trends From January 2020 to December 2023: a Mathematical Modeling

Fayette Klaassen¹, Nicole A Swartwood¹, Melanie H Chitwood²

¹Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

The Journal of Infectious Diseases

|October 23, 2025

Abstract

Background:

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 50 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 30 December 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: 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%).

Conclusion:

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.

Keywords:

SARS-CoV-2 effective protection immunological exposure vaccination

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