Waning protection after vaccination and prior infection against COVID-19-related mortality over 18 months

OBJECTIVES: Evidence on waning patterns in protection from vaccine-induced, infection-induced, and hybrid immunity against death is scarce. The aim of this study is to assess the temporal trends in protection against mortality.

METHODS: Population-based case-control study nested in the total population of Scania Region, Sweden using individual-level registry data of COVID-19-related deaths (<30 days after positive SARS-CoV-2 test) between 27 December 2020 and 3 June 2022. Controls were matched for age, sex, and index date. Conditional logistic regression was used to estimate the preventable fraction (PF) from vaccination (PF vac corresponding to vaccine effectiveness; ≥2 vaccine doses vs. 0 doses), prior infection (PF inf), and hybrid immunity (PF hybrid). PF was calculated as one minus odds ratio. Models were adjusted for comorbidities, long-term care facility residence, prior infection (for PF vac), country of birth, socio-economic conditions, and time since last vaccination (for PF inf).

RESULTS: In total, 14 936 individuals (1440 COVID-19-related deaths and 13 496 controls) were included in the case-control analyses (45% females, median age: 84 years). PF vac was above 90% during the first month after vaccination, regardless of the number of vaccine doses. After 6 months, PF vac of two doses waned to 34% (95% CI: -30% to 66%). PF inf for people surviving a SARS-CoV-2 infection waned from 88% (-16% to 99%) 3 months after infection to 62% (34-79%) after 9 months. No differences in waning patterns in PF vac were seen between virus variants, gender, and age.

DISCUSSION: Given the waning of protection against death, continuous surveillance of population immunity status, particularly among the most vulnerable population groups, could help to further fine-tune vaccination recommendations.