1887
Research Open Access
Like 0

Abstract

Background

Post-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.

Aim

To estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.

Methods

We used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.

Results

Within 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3–7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91–0.94 and RI: 0.96; 95% CI: 0.94–0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95–0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00–1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28–1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97–1.78).

Conclusion

COVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.

Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2023.28.3.2200195
2023-01-19
2023-02-04
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2023.28.3.2200195
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/28/3/eurosurv-28-3-4.html?itemId=/content/10.2807/1560-7917.ES.2023.28.3.2200195&mimeType=html&fmt=ahah

References

  1. Vasileiou E, Simpson CR, Shi T, Kerr S, Agrawal U, Akbari A, et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study. Lancet. 2021;397(10285):1646-57.  https://doi.org/10.1016/S0140-6736(21)00677-2  PMID: 33901420 
  2. Agrawal U, Katikireddi SV, McCowan C, Mulholland RH, Azcoaga-Lorenzo A, Amele S, et al. COVID-19 hospital admissions and deaths after BNT162b2 and ChAdOx1 nCoV-19 vaccinations in 2·57 million people in Scotland (EAVE II): a prospective cohort study. Lancet Respir Med. 2021;9(12):1439-49.  https://doi.org/10.1016/S2213-2600(21)00380-5  PMID: 34599903 
  3. Whitaker HJ, Tsang RSM, Byford R, Andrews NJ, Sherlock J, Sebastian Pillai P, et al. Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response amongst individuals in clinical risk groups. J Infect. 2022;84(5):675-83.  https://doi.org/10.1016/j.jinf.2021.12.044  PMID: 34990709 
  4. Kissling E, Hooiveld M, Martínez-Baz I, Mazagatos C, William N, Vilcu AM, et al. Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021. Euro Surveill. 2022;27(21):2101104.  https://doi.org/10.2807/1560-7917.ES.2022.27.21.2101104  PMID: 35620997 
  5. European Medicines Agency (EMA). Comirnaty. Amsterdam: EMA; 2022. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/comirnaty
  6. European Medicines Agency (EMA). Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Amsterdam: EMA; 2022. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/vaxzevria
  7. European Medicines Agency (EMA). Spikevax (previously COVID-19 Vaccine Moderna). Amsterdam: EMA; 2022. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/spikevax
  8. Department of Health and Social Care. Use of the AstraZeneca COVID-19 (AZD1222) vaccine: updated JCVI statement, 7 May 2021. London: gov.uk; 2021. Available from: https://www.gov.uk/government/publications/use-of-the-astrazeneca-covid-19-vaccine-jcvi-statement-7-may-2021/use-of-the-astrazeneca-covid-19-azd1222-vaccine-updated-jcvi-statement-7-may-2021
  9. Public Health England. COVID-19 vaccine surveillance strategy, March 2021. London: gov.uk; 2021. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/974300/COVID-19_vaccine_surveillance_strategy_March21.pdf
  10. Li R, Stewart B, McNeil MM, Duffy J, Nelson J, Kawai AT, et al. Post licensure surveillance of influenza vaccines in the Vaccine Safety Datalink in the 2013-2014 and 2014-2015 seasons. Pharmacoepidemiol Drug Saf. 2016;25(8):928-34.  https://doi.org/10.1002/pds.3996  PMID: 27037540 
  11. European Medicines Agency (EMA). Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU. Amsterdam: EMA; 2014. Available from: https://www.ema.europa.eu/en/interim-guidance-enhanced-safety-surveillance-seasonal-influenza-vaccines-eu
  12. Bollaerts K, de Smedt T, McGee C, Emborg H-D, Villa M, Alexandridou M, et al. ADVANCE: Towards near real-time monitoring of vaccination coverage, benefits and risks using European electronic health record databases. Vaccine. 2020;38(Suppl 2):B76-83.  https://doi.org/10.1016/j.vaccine.2019.08.012  PMID: 31677951 
  13. de Lusignan S, Jones N, Dorward J, Byford R, Liyanage H, Briggs J, et al. The Oxford Royal College of General Practitioners Clinical Informatics Digital Hub: Protocol to Develop Extended COVID-19 Surveillance and Trial Platforms. JMIR Public Health Surveill. 2020;6(3):e19773.  https://doi.org/10.2196/19773  PMID: 32484782 
  14. de Lusignan S, Damaso S, Ferreira F, Byford R, McGee C, Pathirannehelage S, et al. Brand-specific enhanced safety surveillance of GSK’s Fluarix Tetra seasonal influenza vaccine in England: 2017/2018 season. Hum Vaccin Immunother. 2020;16(8):1762-71.  https://doi.org/10.1080/21645515.2019.1705112  PMID: 32118513 
  15. Simpson CR, Shi T, Vasileiou E, Katikireddi SV, Kerr S, Moore E, et al. First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland. Nat Med. 2021;27(7):1290-7.  https://doi.org/10.1038/s41591-021-01408-4  PMID: 34108714 
  16. Kerr S, Joy M, Torabi F, Bedston S, Akbari A, Agrawal U, et al. First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales. PLoS Med. 2022;19(2):e1003927.  https://doi.org/10.1371/journal.pmed.1003927  PMID: 35192598 
  17. Tippu Z, Correa A, Liyanage H, Burleigh D, McGovern A, Van Vlymen J, et al. Ethnicity recording in primary care computerised medical record systems: an ontological approach. J Innov Health Inform. 2017;23(4):920.  https://doi.org/10.14236/jhi.v23i4.920  PMID: 28346128 
  18. Noble S, McLennan D, Noble M, Plunkett E, Gutacker N, Silk M, et al. The English Indices of Deprivation 2019: Research Report London: Ministry of Housing, Communities and Local Government; 2019. Available from: https://dera.ioe.ac.uk/34264/1/IoD2019_Research_Report.pdf
  19. Whitaker HJ, Hocine MN, Farrington CP. The methodology of self-controlled case series studies. Stat Methods Med Res. 2009;18(1):7-26.  https://doi.org/10.1177/0962280208092342  PMID: 18562396 
  20. Petersen I, Douglas I, Whitaker H. Self controlled case series methods: an alternative to standard epidemiological study designs. BMJ. 2016;354:i4515.  https://doi.org/10.1136/bmj.i4515  PMID: 27618829 
  21. R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2021. Available from: https://www.R-project.org
  22. Wickham H, François R, Henry L, Müller K. dplyr: A Grammar of Data Manipulation. 2021. Available from: https://CRAN.R-project.org/package=dplyr
  23. Grolemund G, Wickham H. Dates and times made easy with lubridate. J Stat Softw. 2011;40(3):1-25.  https://doi.org/10.18637/jss.v040.i03 
  24. Weldeslassie YG, Whitaker H, Farrington P. SCCS: The self-controlled case series method. 2020. Available from: https://CRAN.R-project.org/package=SCCS
  25. Yoshida K, Bartel A. tableone: Create ‘Table 1’ to describe baseline characteristics with or without propensity score weights. R package version 0.12.0. 2020. Available from: https://CRAN.R-project.org/package=tableone
  26. Wickham H. ggplot2: Elegant Graphics for Data Analysis. New York: Springer-Verlag; 2016.
  27. de Lusignan S, Lopez Bernal J, Byford R, Amirthalingam G, Ferreira F, Akinyemi O, et al. Influenza and respiratory virus surveillance, vaccine uptake, and effectiveness at a time of cocirculating COVID-19: Protocol for the English primary care sentinel system for 2020-2021. JMIR Public Health Surveill. 2021;7(2):e24341.  https://doi.org/10.2196/24341  PMID: 33605892 
  28. Pathirannehelage S, Kumarapeli P, Byford R, Yonova I, Ferreira F, de Lusignan S. Uptake of a dashboard designed to give realtime feedback to a sentinel network about key data required for influenza vaccine effectiveness studies. Stud Health Technol Inform. 2018;247:161-5. PMID: 29677943 
  29. de Lusignan S, Tsang RSM, Amirthalingam G, Akinyemi O, Sherlock J, Tripathy M, et al. Adverse events of interest following influenza vaccination, a comparison of cell culture-based with egg-based alternatives: English sentinel network annual report paper 2019/20. Lancet Reg Health Eur. 2021;2:100029.  https://doi.org/10.1016/j.lanepe.2021.100029  PMID: 34557791 
  30. Last JM. Commentary: the iceberg revisited. Int J Epidemiol. 2013;42(6):1613-5.  https://doi.org/10.1093/ije/dyt112  PMID: 24415603 
  31. Bedston S, Akbari A, Jarvis CI, Lowthian E, Torabi F, North L, et al. COVID-19 vaccine uptake, effectiveness, and waning in 82,959 health care workers: A national prospective cohort study in Wales. Vaccine. 2022;40(8):1180-9.  https://doi.org/10.1016/j.vaccine.2021.11.061  PMID: 35042645 
  32. Husby A, Hansen JV, Fosbøl E, Thiesson EM, Madsen M, Thomsen RW, et al. SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study. BMJ. 2021;375:e068665.  https://doi.org/10.1136/bmj-2021-068665  PMID: 34916207 
  33. Karlstad Ø, Hovi P, Husby A, Härkänen T, Selmer RM, Pihlström N, et al. SARS-CoV-2 vaccination and myocarditis in a Nordic cohort study of 23 million residents. JAMA Cardiol. 2022;7(6):600-12.  https://doi.org/10.1001/jamacardio.2022.0583  PMID: 35442390 
  34. Wong H-L, Hu M, Zhou CK, Lloyd PC, Amend KL, Beachler DC, et al. Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases. Lancet. 2022;399(10342):2191-9.  https://doi.org/10.1016/S0140-6736(22)00791-7  PMID: 35691322 
  35. Patone M, Handunnetthi L, Saatci D, Pan J, Katikireddi SV, Razvi S, et al. Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nat Med. 2021;27(12):2144-53.  https://doi.org/10.1038/s41591-021-01556-7  PMID: 34697502 
  36. Frontera JA, Tamborska AA, Doheim MF, Garcia-Azorin D, Gezegen H, Guekht A, et al. Neurological events reported after COVID-19 vaccines: an analysis of vaccine adverse event reporting system. Ann Neurol. 2022;91(6):756-71.  https://doi.org/10.1002/ana.26339  PMID: 35233819 
  37. Allahyari F, Molaee H, Hosseini Nejad J. Covid-19 vaccines and neurological complications: a systematic review. Z Naturforsch C J Biosci. 2023;78(1-2):1-8. Epub ahead of print.  https://doi.org/10.1515/znc-2022-0092  PMID: 36087300 
  38. Andrews NJ, Stowe J, Ramsay MEB, Miller E. Risk of venous thrombotic events and thrombocytopenia in sequential time periods after ChAdOx1 and BNT162b2 COVID-19 vaccines: A national cohort study in England. Lancet Reg Health Eur. 2022;13:100260.  https://doi.org/10.1016/j.lanepe.2021.100260  PMID: 34927118 
  39. Hippisley-Cox J, Patone M, Mei XW, Saatci D, Dixon S, Khunti K, et al. Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. BMJ. 2021;374:n1931.  https://doi.org/10.1136/bmj.n1931  PMID: 34446426 
  40. Xiong X, Yuan J, Li M, Jiang B, Lu ZK. Age and gender disparities in adverse events following COVID-19 vaccination: real-world evidence based on big data for risk management. Front Med (Lausanne). 2021;8:700014.  https://doi.org/10.3389/fmed.2021.700014  PMID: 34350199 
  41. Dagan N, Barda N, Balicer RD. Adverse effects after BNT162b2 vaccine and SARS-CoV-2 infection, according to age and sex. N Engl J Med. 2021;385(24):2299.  https://doi.org/10.1056/NEJMc2115045  PMID: 34706169 
  42. Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, et al. Safety of the BNT162b2 mRNA Covid-19 vaccine in a nationwide setting. N Engl J Med. 2021;385(12):1078-90.  https://doi.org/10.1056/NEJMoa2110475  PMID: 34432976 
  43. Sodhi M, Samii A, Etminan M. A comparative safety study of reported neurological adverse events with three COVID-19 vaccines. J Neurol. 2022;269(5):2301-3.  https://doi.org/10.1007/s00415-021-10919-6  PMID: 34999959 
  44. Miller E. Rapid evaluation of the safety of COVID-19 vaccines: how well have we done? Clin Microbiol Infect. 2022;28(4):477-8.  https://doi.org/10.1016/j.cmi.2021.12.018  PMID: 34999173 
  45. Remschmidt C, Wichmann O, Harder T. Frequency and impact of confounding by indication and healthy vaccinee bias in observational studies assessing influenza vaccine effectiveness: a systematic review. BMC Infect Dis. 2015;15(1):429.  https://doi.org/10.1186/s12879-015-1154-y  PMID: 26474974 
  46. Joy M, McGagh D, Jones N, Liyanage H, Sherlock J, Parimalanathan V, et al. Reorganisation of primary care for older adults during COVID-19: a cross-sectional database study in the UK. Br J Gen Pract. 2020;70(697):e540-7.  https://doi.org/10.3399/bjgp20X710933  PMID: 32661009 
  47. Tu K, Sarkadi Kristiansson R, Gronsbell J, de Lusignan S, Flottorp S, Goh LH, et al. Changes in primary care visits arising from the COVID-19 pandemic: an international comparative study by the International Consortium of Primary Care Big Data Researchers (INTRePID). BMJ Open. 2022;12(5):e059130.  https://doi.org/10.1136/bmjopen-2021-059130  PMID: 35534063 
  48. Ford E, Carroll JA, Smith HE, Scott D, Cassell JA. Extracting information from the text of electronic medical records to improve case detection: a systematic review. J Am Med Inform Assoc. 2016;23(5):1007-15.  https://doi.org/10.1093/jamia/ocv180  PMID: 26911811 
  49. Deady M, Ezzeldin H, Cook K, Billings D, Pizarro J, Plotogea AA, et al. The Food and Drug Administration biologics effectiveness and safety initiative facilitates detection of vaccine administrations from unstructured data in medical records through natural language processing. Front Digit Health. 2021;3:777905.  https://doi.org/10.3389/fdgth.2021.777905  PMID: 35005697 
  50. Tran Kiem C, Andronico A, Bosetti P, Paireau J, Alter L, Boëlle P-Y, et al. Benefits and risks associated with different uses of the COVID-19 vaccine Vaxzevria: a modelling study, France, May to September 2021. Euro Surveill. 2021;26(26):2100533.  https://doi.org/10.2807/1560-7917.ES.2021.26.26.2100533  PMID: 34212840 
  51. Centers for Disease Control and Prevention (CDC). Advisory Committee on Immunization Practices (ACIP): Coronovirus Disease 2019 (COVID-19) Vaccines. ACIP Presentation Slides: June 23-25, 2021 Meeting. Atlanta: CDC; 2021. Available from: https://www.cdc.gov/vaccines/acip/meetings/slides-2021-06.html
/content/10.2807/1560-7917.ES.2023.28.3.2200195
Loading

Data & Media loading...

Supplementary data

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error