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Adverse Events After COVID-19 Vaccination
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This interim analysis of surveillance data examined 6.2 million vaccine-eligible members from eight participating US health plans to study the potential impact of mRNA vaccination on 23 serious outcomes occurring 1 to 21 days after the vaccine dose compared with 22 to 42 days after the vaccine dose. The incidence per 1,000,000 person-years 1 to 21 days post vaccination versus 22 to 42 days post vaccination was 1612 versus 1781 (RR, 0.97) for ischemic stroke, 952 versus 896 (RR, 1.16) for VTE, 45 versus 69 (RR, 0.70) for disseminated intravascular coagulation, and 9 versus 6 (RR, 2.60) for TTP. There were 10 cerebral venous sinus thrombosis cases, but these were not associated with thrombocytopenia.
- In this interim analysis, the incidence of serious outcomes was not significantly higher 1 to 21 days post vaccination compared with 22 to 42 days post vaccination.
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy.
Objectives
To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population.
Design, Setting, and Participants
This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021.
Exposures
Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2.
Main Outcomes and Measures
Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted.
Results
A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273.
Conclusions and Relevance
In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.
Additional Info
Disclosure statements are available on the authors' profiles:
Surveillance for Adverse Events After COVID-19 mRNA Vaccination
JAMA 2021 Sep 03;[EPub Ahead of Print], NP Klein, N Lewis, K Goddard, B Fireman, O Zerbo, KE Hanson, JG Donahue, EO Kharbanda, A Naleway, JC Nelson, S Xu, WK Yih, JM Glanz, JTB Williams, SJ Hambidge, BJ Lewin, TT Shimabukuro, F DeStefano, ES WeintraubFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This paper, using an administrative database updated weekly, surveyed 23 adverse events that developed among approximately 6,200,000 persons within 21 days and 22 to 42 days after doses 1 and 2 of the COVID-19 mRNA vaccines BNT162b2 and mRNA-1273. Several of the adverse events are of great interest to hematologists and their patients, such as ITP, venous thromboembolism, PE, cerebral venous thrombosis, arterial thromboembolism, hemorrhagic stroke, DIC, and the thrombosis with thrombocytopenia syndrome. In no case was there a difference in the number of these adverse events between days 0 and 21 and 22 and 42, indicating that vaccination using mRNA vaccines is not associated with these hematological toxicities. Such results are consistent with a previously described study using a smaller administrative database,1,2 although another analysis using a larger administrative database identified an increased number of arterial thromboembolic events—but not any of the other hematological adverse events—within 14 days of the first dose of BNT162b2.3 Despite this ambiguity and the potential uncertainties and threats that it may pose, it is unambiguous that the benefit–risk of mRNA vaccines (as well as adenoviral vector-based vaccines that have been associated with rare hematological toxicities1,3) is very favorable, as the hematological problems surveyed are far more frequent with COVID-19 infection than with COVID-19 vaccination using these delivery systems.3,4
References