Factors Limiting the Success of an All-Variant COVID-19 Vaccine: A Simulation Study

This paper simulates a hypothetical pan-coronavirus vaccine that confers immediate sterilizing immunity against all SARS-CoV-2 variants. Simulations used a SEIIS spreadsheet model that ran two parallel subpopulations: one that accepted vaccination, and another that refused it. The two subpopulations could transmit infections to one another. Using data from the United States (US), the simulated vaccine was tested against limiting factors such as vaccine hesitancy, slow vaccination distribution, and the development of high-transmission variants. The vaccine was often successful at reducing cases, but high-transmission variants and discontinuation of non-pharaceutical interventsions (NPIs) such as masking greatly elevated cases. A puzzling outcome was that if NPIs are discontinued and high-transmission variants become common, the model predicted consistently higher rates of disease than are actually observed in the US in 2024. However, if cumulative exposure to virus antigens increases the duration of immunity or decreases the infectivity of the virus, the model predictions were brought back into a more realistic range. The major finding was that even when a COVID vaccine always produces sterilizing immunity against every SARS-CoV-2 variant, its ability to control the epidemic can be compromised by multiple common conditions.