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. 2021 Aug 13;2(8):965-978.e5.
doi: 10.1016/j.medj.2021.06.006. Epub 2021 Jul 1.

Real-time analysis of a mass vaccination effort confirms the safety of FDA-authorized mRNA COVID-19 vaccines

Reid McMurry  1 , Patrick Lenehan  1 , Samir Awasthi  1 , Eli Silvert  1 , Arjun Puranik  1 , Colin Pawlowski  1 , A J Venkatakrishnan  1 , Praveen Anand  2 , Vineet Agarwal  1 , John C O'Horo  3 , Gregory J Gores  3 , Amy W Williams  3 , Andrew D Badley  3 , John Halamka  3 , Abinash Virk  3 , Melanie D Swift  3 , Katie Carlson  1 , Deeksha Doddahonnaiah  1 , Anna Metzger  1 , Nikhil Kayal  1 , Gabi Berner  1 , Eshwan Ramudu  1 , Corinne Carpenter  1 , Tyler Wagner  1 , Ajit Rajasekharan  1 , Venky Soundararajan  1   2
Affiliations

Real-time analysis of a mass vaccination effort confirms the safety of FDA-authorized mRNA COVID-19 vaccines

Reid McMurry et al. Med. .

Abstract

Background: As the coronavirus disease 2019 (COVID-19) vaccination campaign unfolds, it is important to continuously assess the real-world safety of Food and Drug Administration (FDA)-authorized vaccines. Curation of large-scale electronic health records (EHRs) enables near-real-time safety evaluations that were not previously possible.

Methods: In this retrospective study, we deployed deep neural networks over a large EHR system to automatically curate the adverse effects mentioned by physicians in over 1.2 million clinical notes between December 1, 2020 and April 20, 2021. We compared notes from 68,266 individuals who received at least one dose of BNT162b2 (n = 51,795) or mRNA-1273 (n = 16,471) to notes from 68,266 unvaccinated individuals who were matched by demographic, geographic, and clinical features.

Findings: Individuals vaccinated with BNT162b2 or mRNA-1273 had a higher rate of return to the clinic, but not the emergency department, after both doses compared to unvaccinated controls. The most frequently documented adverse effects within 7 days of each vaccine dose included myalgia, headache, and fatigue, but the rates of EHR documentation for each side effect were remarkably low compared to those derived from active solicitation during clinical trials. Severe events, including anaphylaxis, facial paralysis, and cerebral venous sinus thrombosis, were rare and occurred at similar frequencies in vaccinated and unvaccinated individuals.

Conclusions: This analysis of vaccine-related adverse effects from over 1.2 million EHR notes of more than 130,000 individuals reaffirms the safety and tolerability of the FDA-authorized mRNA COVID-19 vaccines in practice.

Funding: This study was funded by nference.

Keywords: BNT162b2; COVID-19; COVID-19 vaccines; mRNA-1273; propensity score matching; real world analysis; vaccine safety.

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Conflict of interest statement

R.M., P.L., E.S., A.P., S.A., C.P., V.A., A.J.V., P.A., A.R., C.C., K.C., D.D., N.K., E.R., G.B., A.M., T.W., and V.S. are employees of nference and have financial interests in the company and in the successful application of this research. R.M. is a student at Boston University School of Medicine. P.L. is a student at Harvard Medical School. J.C.O. receives personal fees from Elsevier and Bates College and small grants from nference outside 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., G.J.G., A.W.W., A.V., M.D.S., 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 illustration of participant selection and study design The vaccinated cohort is composed 68,266 individuals from the Mayo Clinic and associated health systems who received at least one dose of BNT162b2 (Pfizer/BioNTech; n = 51,795) or mRNA-1273 (Moderna; n = 16,471) between December 1, 2020 and April 20, 2021 and did not test positive for SARS-CoV-2 prior to their first vaccination. A control cohort of unvaccinated individuals was generated via a combination of exact matching parameters and one-to-one propensity score matching, yielding 68,266 individuals with similar distributions of age, sex, race, ethnicity, residential location, number of prior influenza and SARS-CoV-2 PCR tests in the past year, and current long-term care residence status. For each cohort, the incidence rates of several adverse effects (e.g., myalgia) were calculated for the 7 days following the first dose and, separately, for the 7 days following the second dose. For a given adverse effect, the incidence rate ratio (IRR) and the corresponding 95% confidence interval (CI) were calculated to determine whether individuals receiving BNT162b2 or mRNA-1273 were more likely to experience the event during these intervals than their matched unvaccinated controls. Incidence rates and IRRs were also calculated for the 14 and 21 days following each vaccine dose.
Figure 2
Figure 2
IRRs for all surveyed adverse effects in vaccinated versus matched unvaccinated cohorts within 7 days of each vaccine dose IRRs are shown with their corresponding 95% CIs for BNT162b2 on the left (ndose 1 = 51,732; ndose 2 = 39,045) and mRNA-1273 on the right (ndose 1 = 16,455; ndose 2 = 11,849). Data correspond to Tables 3 and 4. A log2(IRR) value greater than 0 indicates that the incidence rate of the given event was higher in the vaccinated cohort, while a value less than 0 indicates that the incidence rate was higher in the unvaccinated cohort.
Figure 3
Figure 3
IRRs for all surveyed adverse effects in vaccinated versus matched unvaccinated cohorts within 14 or 21 days of each vaccine dose IRRs are shown with their corresponding 95% CIs for BNT162b2 (ndose 1 = 51,732; ndose 2 = 39,045) on the left and mRNA-1273 (ndose 1 = 16,455; ndose 2 = 11,849) on the right. (A) IRRs within 14 days of each vaccine dose, corresponding to data shown in Tables S7 and S8. (B) IRRs within 21 days of each vaccine dose, corresponding to data shown in Tables S9 and S10. A log2(IRR) value greater than 0 indicates that the incidence rate of the given event was higher in the vaccinated cohort, while a value less than 0 indicates that the incidence rate was higher in the unvaccinated cohort. See also Tables S7–S10.
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