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. 2021 Aug 13;2(8):979-992.e8.
doi: 10.1016/j.medj.2021.06.007. Epub 2021 Jun 29.

FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system

Colin Pawlowski  1 , Patrick Lenehan  1 , Arjun Puranik  1 , Vineet Agarwal  1 , A J Venkatakrishnan  1 , Michiel J M Niesen  1 , John C O'Horo  2 , Abinash Virk  2 , Melanie D Swift  2 , Andrew D Badley  2 , John Halamka  2 , Venky Soundararajan  1
Affiliations

FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system

Colin Pawlowski et al. Med. .

Abstract

Background: Two US Food and Drug Administration (FDA)-authorized coronavirus disease 2019 (COVID-19) mRNA vaccines, BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), have demonstrated high efficacy in large phase 3 randomized clinical trials. It is important to assess their effectiveness in a real-world setting.

Methods: This is a retrospective analysis of 136,532 individuals in the Mayo Clinic health system (Arizona, Florida, Iowa, Minnesota, and Wisconsin) with PCR testing data between December 1, 2020 and April 20, 2021. We compared clinical outcomes for a vaccinated cohort of 68,266 individuals who received at least one dose of either vaccine (nBNT162b2 = 51,795; nmRNA-1273 = 16,471) and an unvaccinated control cohort of 68,266 individuals propensity matched based on relevant demographic, clinical, and geographic features. We estimated real-world vaccine effectiveness by comparing incidence rates of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR testing and COVID-19-associated hospitalization and intensive care unit (ICU) admission starting 7 days after the second vaccine dose.

Findings: The real-world vaccine effectiveness of preventing SARS-CoV-2 infection was 86.1% (95% confidence interval [CI]: 82.4%-89.1%) for BNT162b2 and 93.3% (95% CI: 85.7%-97.4%) for mRNA-1273. BNT162b2 and mRNA-1273 were 88.8% (95% CI: 75.5%-95.7%) and 86.0% (95% CI: 71.6%-93.9%) effective in preventing COVID-19-associated hospitalization. Both vaccines were 100% effective (95% CIBNT162b2: 51.4%-100%; 95% CImRNA-1273: 43.3%-100%) in preventing COVID-19-associated ICU admission.

Conclusions: BNT162b2 and mRNA-1273 are effective in a real-world setting and are associated with reduced rates of SARS-CoV-2 infection and decreased burden of COVID-19 on the healthcare system.

Funding: This study was funded by nference.

Keywords: COVID-19; COVID-19 vaccines; propensity score matching; real world evidence.

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Conflict of interest statement

C.P., P.L., A.P., V.A., A.V., M.J.M.N., and V.S. are employees of nference and have financial interests in the company and in the successful application of this research. J.C.O. receives personal fees from Elsevier and Bates College and small grants from nference, Inc., outside of the submitted work. A.D.B. is a consultant for Abbvie, is on scientific advisory boards for nference and Zentalis, and is founder and President of Splissen Therapeutics. J.H., J.C.O., M.D.S., A.V., and A.D.B. are employees of the Mayo Clinic. The Mayo Clinic may stand to gain financially from the successful outcome of the research. nference collaborates with Janssen and other bio-pharmaceutical companies on data science initiatives unrelated to this study. These collaborations had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies.

Figures

None
Graphical abstract
Figure 1
Figure 1
Schematic illustrating the algorithms for participant selection and outcome assessment (A) Design of the study to compare SARS-CoV-2 infection rates in individuals receiving BNT162b2 or mRNA-1273 vaccination compared with 1-to-1 propensity-matched unvaccinated individuals (nBNT162b2 = 51,795 per group; nmRNA-1273 = 16,471 per group). For each group, incidence rates were calculated to assess the effectiveness of vaccination in preventing a positive SARS-CoV-2 PCR test at least 7 days after the second vaccine dose. Several other time windows were also evaluated for vaccine effectiveness. (B) Design of the study to compare COVID-19 disease severity in individuals who were fully vaccinated at least 14 days prior to diagnosis with COVID-19 (n = 81) and had at least 21 days of follow-up after diagnosis (n = 32) versus 1-to-2 propensity-matched unvaccinated individuals (n = 162) with at least 21 days of follow-up (n = 150). Hospitalization and ICU admission were assessed within 21 days of PCR diagnosis, and mortality was assessed within 28 days of PCR diagnosis.
Figure 2
Figure 2
Kaplan-Meier analyses to assess cumulative incidence of SARS-CoV-2 infection between vaccinated and unvaccinated cohorts Cumulative incidence at time t is the estimated proportion of individuals who had a positive SARS-CoV-2 PCR test on or before time t (i.e., 1 minus the standard Kaplan-Meier survival estimate). (A) For BNT162b2, cumulative incidence of positive SARS-CoV-2 testing from 7 days after the date of the first dose until the date of the second dose, the date of censoring, or the end of the study period (whichever occurs first for a given matched pair). A log rank test rejects the null hypothesis of equal hazard rates (p = 2.3 × 10−17). (B) For BNT162b2, cumulative incidence of positive SARS-CoV-2 testing from 7 days after the second dose until the end of the study period. A log rank test rejects the null hypothesis of equal hazard rates (p = 7.3 × 10−85). (C) Same as in (A) but for mRNA-1273. A log rank test rejects the null hypothesis of equal hazard rates (p = 1.0 × 10−8). (D) Same as in (B) but for mRNA-1273. A log-rank test rejects the null hypothesis of equal hazard rates (p = 2.9 × 10−20). In all cases, the cumulative incidence is compared between vaccinated individuals and their matched unvaccinated controls over the same time period.
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