Effectiveness of a fourth dose of mRNA COVID-19 vaccine against all-cause mortality in long-term care facility residents and in the oldest old: A nationwide, retrospective cohort study in Sweden

Background The effect of a fourth dose of COVID-19 vaccine on the risk of death in the oldest and frailest individu -als is unknown.Methods Two matched cohorts were formed using Swedish nationwide registers. In the first, residents of long-term care facilities (LTCFs) given a fourth dose of an mRNA vaccine from 1 January 2022 onwards were matched 1:1 on birth year and county of residence to residents given at least a third dose (N = 24,524). In the second, all individuals aged >= 80 years given a fourth dose were matched 1:1 to individuals given at least a third dose (N = 394,104). Cox regression models were used to estimate hazard ratios for all-cause mortality in fourth-dose recipients as compared with in third-dose recipients, with relative vaccine effectiveness (VE) estimated as 1 minus the hazard ratio.Findings From 7 days after baseline and onwards, there were 1119 deaths in the LTCF cohort during a median fol-low-up of 77 days and a maximum follow-up of 126 days. During days 7 to 60, the VE of the fourth dose was 39% (95% CI, 29-48), which declined to 27% (95% CI,-2-48) during days 61 to 126. In the cohort of all individuals aged >= 80 years, there were 5753 deaths during a median follow-up of 73 days and a maximum follow-up of 143 days. Dur-ing days 7 to 60, the VE of the fourth dose was 71% (95% CI, 69-72), which declined to 54% (95% CI, 48-60) during days 61 to 143. The VE of the fourth dose seemed stronger when it was compared to third-dose recipients where at least four months had passed since vaccination (P < 0 cent 001 for interaction).Interpretation As compared with a third dose, a fourth dose of an mRNA COVID-19 vaccine, administered during the Omicron era, was associated with reduced risk of death from all causes in residents of LTCFs and in the oldest old dur-ing the first two months, after which the protection became slightly lower. These findings suggest that a fourth dose may prevent premature mortality in the oldest and frailest even after the emergence of the Omicron variant, although the timing of vaccination seems to be important with respect to the slight waning observed after two months.Funding There was no funding source for this study.Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Automated summary

This study examined the impact of a fourth dose of COVID-19 vaccine on the risk of death, finding that the fourth dose significantly reduced the risk of death in residents of long-term care facilities and individuals aged 80 and older in the first two months, but the protection slightly decreased over time.