A comparison of alternative vaccination strategies for protecting those vulnerable to illness, hospitalization, or death upon infection with SARS-CoV-2: A metapopulation modeling study

BackgroundU.S. vaccination policymakers initially prioritized healthcare, other frontline essential workers, and those at greatest risk of severe COVID-19. Protection may be direct, by decreasing susceptibility to infection if exposed, or indirect, by decreasing the risk of exposure through the vaccination of others. MethodsWe modified our published SARS-CoV-2 transmission model by including immunity-moderated disease, updating some parameters, and making others time-varying. Then we derived the metapopulation reproduction numbers and related analytical quantities and compared the respective impacts of protecting vulnerable people directly and indirectly from 14 December 2020, when vaccination began, to 11 May 2024, when the Public Health Emergency ended. FindingsA greater proportion of young people, particularly adolescents, had antibodies to nucleocapsid protein than adults before schools reopened for the 2021-22 school year, their vaccination lagged far behind that of older people, especially during the Omicron epoch, and they caused more infections. Nonetheless, we found that, while vaccinating to reduce transmission averted more infections, the actual vaccination strategy averted more illnesses, hospitalizations, and deaths. InterpretationBecause of the age-dependence of severe COVID-19, which policy was designed to mitigate, vaccinating older people was more effective than vaccinating the younger ones who might otherwise have infected them. This result would not hold if, contrary to presently available evidence, the effectiveness of vaccination or duration of vaccine-induced immunity varied inversely with age. FundingWe used two nationwide, CDC-funded, serological surveys. Except for Professor Day, the authors are (or were) U.S. government employees whose research is (or was) not funded independently. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe utility of vaccination in reducing infections or infectiousness and mitigating disease is well known. The rapidity with which astonishingly effective mRNA vaccines against COVID-19 were produced is among the greatest scientific achievements of our lifetimes. Less well known is how to deploy these public health tools most effectively. When, for example, is indirect versus direct protection indicated? Added value of this studyWe used a validated SARS-CoV-2 transmission model to compare the actual COVID-19 vaccination program in the United States with a hypothetical alternative designed to reduce transmission. We assumed that the effectiveness of vaccination and duration of immunity, infection- or vaccination-derived, were age-independent. We found that, in terms of protecting those at greatest risk of severe disease, the actual vaccination program outperformed the alternative strategy. Implications of all the available evidenceWhile the immunological response to first doses of COVID-19 vaccine may be less robust among older than younger recipients, available evidence indicates that, after the second or third doses, immunity is comparable. As this may not always be true, protecting elderly and other immunocompromised people by vaccinating those who might otherwise infect them warrants consideration.