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Mortality risk after COVID-19 vaccination: A self-controlled case series study
Stanley Xu1, Lina S Sy2, Vennis Hong2
1Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, United States; Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, United States.
Insights
COVID-19 vaccination showed no increased risk of death from any cause or cardiac events. This study analyzed mortality following primary COVID-19 vaccine series in the US, finding no significant safety concerns.
Area of Science:
- Epidemiology
- Vaccine Safety Research
- Public Health
Background:
- Previous studies on COVID-19 vaccination and mortality risk had potential residual confounding.
- A modified self-controlled case series (SCCS) design was employed to mitigate bias.
- The study focused on non-COVID-19 mortality, all-cause mortality, and specific cardiac-related death outcomes.
Purpose of the Study:
- To assess the risk of non-COVID-19 mortality after primary COVID-19 vaccination.
- To evaluate the risk of all-cause mortality following COVID-19 vaccination.
- To examine the risk of four cardiac-related death outcomes post-COVID-19 vaccination.
Main Methods:
- Utilized a modified SCCS design analyzing deaths from December 2020 to August 2021 across eight Vaccine Safety Datalink sites.
- Calculated relative incidences (RI) for various mortality outcomes after primary COVID-19 vaccine series (Pfizer-BioNTech, Moderna, Janssen).
- Adjusted for seasonality using calendar month and included unvaccinated individuals in analyses, with primary (28-day) and secondary (14-day) risk intervals.
Main Results:
- For Pfizer-BioNTech and Moderna vaccines, relative incidences for all-cause and non-COVID-19 mortality were below 1, with confidence intervals excluding 1.
- For Moderna, two cardiac-related mortality estimates had confidence intervals including 1 (RI=0.78-0.80) 14 days post-second dose in specific subgroups.
- For Janssen vaccine, relative incidences for cardiac-related deaths ranged from 0.68-0.98, with confidence intervals including 1.
Conclusions:
- The modified SCCS design, accounting for temporal trends, found no increased risk of non-COVID-19 mortality or all-cause mortality after primary COVID-19 vaccination.
- No increased risk was identified for four specific cardiac-related death outcomes among recipients of the three main US COVID-19 vaccines.
- The findings support the safety of primary COVID-19 vaccine series regarding mortality risk.
Background:
Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination.
Methods:
We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models.
Results:
For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1.
Conclusion:
Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.
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