Prior infections and effectiveness of SARS-CoV-2 vaccine in test-negative studies: a systematic review and meta-analysis

Prior infection with SARS-CoV-2 can provide protection against infection and severe COVID-19. We aimed to determine the impact of preexisting immunity on vaccine effectiveness (VE) estimates. We systematically reviewed and meta-analyzed 66 test-negative design studies that examined VE against infection or severe disease (hospitalization, intensive care unit admission, or death) for primary vaccination series. Pooled VE among studies that included people with prior COVID-19 infection was lower against infection (77%; 95% CI, 72-81) and severe disease (86%; 95% CI, 83-89) compared with studies that excluded people with prior COVID-19 infection (pooled VE against infection: 87% [95% CI, 85-89]; pooled VE against severe disease: 93% [95% CI, 91-95]). There was a negative correlation between VE estimates against infection and severe disease, and the cumulative incidence of cases before the start of the study or incidence rates during the study period. We found clear empirical evidence that higher levels of preexisting immunity were associated with lower VE estimates. Prior infections should be treated as both a confounder and effect modificatory when the policies target the whole population or are stratified by infection history, respectively.