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. 2021 Oct 12;326(14):1390-1399.
doi: 10.1001/jama.2021.15072.

Surveillance for Adverse Events After COVID-19 mRNA Vaccination

Nicola P Klein  1 , Ned Lewis  1 , Kristin Goddard  1 , Bruce Fireman  1 , Ousseny Zerbo  1 , Kayla E Hanson  2 , James G Donahue  2 , Elyse O Kharbanda  3 , Allison Naleway  4 , Jennifer Clark Nelson  5 , Stan Xu  6 , W Katherine Yih  7 , Jason M Glanz  8   9 , Joshua T B Williams  10   11 , Simon J Hambidge  10   11 , Bruno J Lewin  6 , Tom T Shimabukuro  12 , Frank DeStefano  12 , Eric S Weintraub  12
Affiliations

Surveillance for Adverse Events After COVID-19 mRNA Vaccination

Nicola P Klein et al. JAMA. .

Abstract

Importance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Klein reported receiving grants from the Centers for Disease Control and Prevention (CDC) during the conduct of the study, and grants from Pfizer, Merck, GSK, Sanofi Pasteur, and Protein Science (now SP) outside the submitted work. Ms Hanson reported receiving grants from CDC during the conduct of the study. Dr Donahue reported receiving grants from CDC during the conduct of the study and from Janssen Vaccines & Prevention for a study unrelated to COVID-19 vaccines. Dr Kharbanda reported receiving other from CDC (contract 200-2012-53526) during the conduct of the study. Dr Naleway reported receiving grants from CDC during the conduct of the study and grants from Pfizer outside the submitted work. Dr Nelson reported receiving grants from Moderna outside the submitted work. Dr Yih reported receiving grants from Pfizer outside the submitted work. Dr Williams reported receiving grants from CDC Vaccine Safety Datalink COVID-19 Infrastructure Funding during the conduct of the study. Dr Lewin reported receiving grants from CDC Vaccine Safety Datalink during the conduct of the study. No other disclosures were reported.

Comment in

References

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