Publication date: Apr 28, 2025
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.
| Concepts | Keywords |
|---|---|
| Floridahealth | Bnt162b2 |
| Hispanic | Covid |
| Italian | Deaths |
| Outpatient | Doi |
| Florida | |
| Medrxiv | |
| Mortality | |
| Mrna | |
| Outcomes | |
| Preprint | |
| Recipients | |
| Risk | |
| Vaccination | |
| Vaccine | |
| Vaccines |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| disease | IDO | intervention |
| drug | DRUGBANK | Methionine |
| disease | MESH | infection |
| disease | MESH | death |
| disease | IDO | facility |
| disease | IDO | algorithm |
| disease | MESH | suicide |
| disease | MESH | social vulnerability |
| drug | DRUGBANK | Isoxaflutole |
| disease | IDO | history |
| disease | IDO | geographical region |
| disease | MESH | ischemic stroke |
| disease | MESH | myocarditis |
| disease | IDO | site |
| disease | IDO | process |
| disease | MESH | uncertainty |
| disease | MESH | syncope |
| disease | MESH | clinical significance |
| drug | DRUGBANK | BCG vaccine |
| disease | MESH | tuberculosis |
| pathway | KEGG | Tuberculosis |
| disease | MESH | measles |
| pathway | KEGG | Measles |
| disease | MESH | amnesia |
| disease | MESH | polio |
| pathway | REACTOME | Immune System |
| disease | MESH | diphtheria |
| disease | MESH | tetanus |
| disease | MESH | pertussis |
| pathway | KEGG | Pertussis |