Tools for Practice

#292 COVID-19 Vaccine Adverse Events

What does real world evidence tell us about adverse effects from available COVID-19 vaccines?

Best evidence finds systemic adverse events related to COVID-19 vaccines are mostly short-lived and differ by type of vaccine, dose given, age, and gender. Anaphylaxis to mRNA vaccines occurs in 2.5 to 5 per million doses. Vaccine-induced thrombotic thrombocytopenia (VITT) is associated with viral vector vaccines (AstraZeneca or Johnson and Johnson). Best estimates of incidence: ~0.5 to 2 per 100,000 and more commonly in women.

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  • From published prospective or retrospective cohort/case control studies.
  • General systemic adverse events:
    • Best evidence from solicited adverse events up to 8 days post-dose in 655,590 patients with Pfizer (2 doses) or AstraZeneca (1 dose) adults:1
      • Most commonly short lived and last 1-2 days:
        • Fatigue, headache: Each 13-23%.
        • Adverse events more common among:
          • Recipients of AstraZeneca (versus Pfizer), Pfizer second dose versus first.
          • Individuals 55 or younger.
          • Women.
        • Similar findings in clinical trials.2
      • Anaphylaxis risk: Based on ~10 million Pfizer doses, ~8 million Moderna.3
        • Incidence (per million doses): 5 (Pfizer), 2.5 (Moderna).
          • 1/3 reported previous anaphylaxis episodes, ~80% with known allergies.
          • No deaths reported.
  • VITT:
    • VITT leading to rare thromboses, particularly cerebral venous sinus thrombosis (CVST), 4-28 days post AstraZeneca vaccine.
      • Risk varies4,5 from 0.4 per 100,000 in 80+ years to ~2 per 100,000 in 20-49.
      • Majority in women under 60 within 14 days of vaccination.5
    • Cohort of 281,264 AstraZeneca recipients in Denmark/Norway6 calculated thrombosis events in excess of natural background risk:
      • Additional venous thromboembolisms (includes deep venous thrombosis, pulmonary embolism and CVST) possibly attributed to vaccine: 11 per 100,000 doses and mostly in women.
  • Suspect VITT if AstraZeneca or Johnson & Johnson vaccine 4-28 days prior, signs/symptoms or positive imaging of serious thrombosis with thrombocytopenia.7
    • Diagnosis confirmed with positive heparin-induced thrombocytopenia assay.4,7
    • Clinical pathways available to guide approach to suspected VITT8:
  • Patient decision tool for AstraZeneca vaccine available:9
  • To report possible vaccine related adverse events in Canada:10

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  • Alex Singer MB BCh BAO CCFP
  • Jennifer Young MD CCFP
  • Michael R Kolber MD CCFP MSc
  • Nicolas Dugré PharmD MSc BCPAC
  • Paul Fritsch MD CCFP
  • Tony Nickonchuk BScPharm

1. Menni C, Klaser K, May A, et al. Lancet Infect Dis. 2021 Apr 27; S1473-3099(21)00224-3. Online ahead of print.

2. Kolber MR, Fritch P, Price M, et al. Can Fam Physician. 2021; 67:185.

3. Shimabukuro TT, Cole M, Su JR. JAMA 2021; 325(11):1101-1102.

4. Cines DB, Bussel JB. N Engl J Med. 2021 Apr 16; NEJMe2106315. Online ahead of print.

5. European Medicines Agency Committee for Medicinal Products for Human Use. Vol 4.; 2021. Available at: Accessed May 15, 2021.

6. Pottegård A, Lund LC, Karlstad Ø, et al. BMJ 2021; 373:n1114.

7. American Society of Hematology. Thrombosis with Thrombocytopenia Syndrome Available at: Accessed May 20, 2021.

8. British Columbia COVID-19 Therapeutics Committee. Vaccine-Induced Immune Thrombotic Thrombocytopenia Guidance. Vol 4.; 2021. Available at: Accessed May 25, 2021.

9. European Medicines Agency Committee for Medicinal Products for Human Use. 2021; 4(23):1-12. Available at: Accessed May 25, 2021.

10. Health Canada. Contact information for Adverse Events Following Immunization (AEFI). Available at: Accessed June 1, 2021.

Authors do not have any conflicts of interest to declare.