ABSTRACT
Objective To examine the relative impact of the initial series of the messenger RNA (mRNA) BNT162b2 (Pfizer) and mRNA-1273 (Moderna) on all-cause and non-COVID-19 mortality among Florida residents.
Design Matched cohort with cumulative and adjusted assessments of risk over 12 month follow up.
Setting Florida’s state-level public health databases with records about COVID-19 vaccination, sociodemographic characteristics of vaccine recipients, location of vaccination, and vital statistics.
Participants Matched cohort of 1,470,100 noninstitutionalized adult Florida residents receiving at least two doses, less than six weeks apart, of either the BNT162b2 or mRNA-1273 mRNA vaccine between December 18, 2020, and August 31, 2021.
Intervention Initial vaccination with two doses of either BNT162b2 or mRNA-1273
Main outcome measures All-cause, cardiovascular, COVID-19, and non-COVID-19 mortality within 12 months after the second COVID-19 vaccine dose
Results There were 9,162,484 noninstitutionalized adult Florida residents who met inclusion criteria, including 5,328,226 BNT162b2 vaccine recipients and 3,834,258 mRNA-1273 vaccine recipients. A total of 1,470,100 vaccinees were matched 1-to-1 based on seven criteria, including census tract. Compared with mRNA-1273 recipients, BNT162b2 recipients had significantly higher risk for all-cause mortality (847.2 vs. 617.9 deaths per 100,000; odds ratio, OR [95% CI]: 1.384 [1.331, 1.439]), cardiovascular mortality (248.7 vs. 162.4 deaths per 100,000 persons; OR [95% CI]: 1.540 [1.431, 1.657]), COVID-19 mortality (55.5 vs. 29.5 deaths per 100,000 persons; OR [95% CI]: 1.882 [1.596, 2.220]) and non-COVID-19 mortality (791.6 vs. 588.4 deaths per 100,000 persons; OR [95% CI]: 1.356 [1.303, 1.412]). Negative control outcomes did not show any indication of meaningful unobserved residual confounding.
Conclusion Florida adults who received BNT162b2 had significantly higher risk of 12-month all-cause, cardiovascular, COVID-19, and non-COVID-19 mortality compared to matched mRNA-1273 recipients. These findings are suggestive of differential non-specific effects of the BNT162b2 and mRNA-1273 COVID-19 vaccines, and potential concerning adverse effects on all-cause and cardiovascular mortality. They underscore the need to evaluate vaccines using clinical endpoints that extend beyond their targeted diseases.
What is already known on this topic
Vaccines may have health effects beyond the diseases they target, including potential effects on all-cause mortality.
The relative impact of the initial series of the messenger RNA (mRNA) BNT162b2 (Pfizer) and mRNA-1273 (Moderna) on all-cause and non-COVID-19 mortality is not well-studied.
What this topic adds
Florida adults who received BNT162b2 had significantly higher risk of 12-month all-cause, cardiovascular, COVID-19, and non-COVID-19 mortality compared to carefully matched mRNA-1273 recipients.
These findings are suggestive of differential non-specific effects of the BNT162b2 and mRNA-1273 COVID-19 vaccines, and potential concerning adverse effects on all-cause and cardiovascular mortality.
Competing Interest Statement
MJ, FM, and JL were supported by the Florida Department of Health and JL serves as State Surgeon General; RL has a financial relationship with Bluebell Foundation/Chicago Community Trust; there are no other relationships or activities that could appear to have influenced the submitted work.
Funding Statement
The study did not receive any external funding.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The institutional review board of the Florida Department of Health gave for this study, and deemed it exempt as public health practice.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Data Availability
The study is based on data from the Florida Department of Health and is prohibited by statute from sharing in its raw form.
