Effectiveness and durability of protection against future SARS-CoV-2 infection conferred by COVID-19 vaccination and previous infection; findings from the UK SIREN prospective cohort study of healthcare workers March 2020 to September 2021

  1. Victoria Hall
  2. Sarah Foulkes
  3. Ferdinando Insalata
  4. Ayoub Saei
  5. Peter Kirwan
  6. Ana Atti
  7. Edgar Wellington
  8. Jameel Khawam
  9. Katie Munro
  10. Michelle Cole
  11. Caio Tranquillini
  12. Andrew Taylor-Kerr
  13. Nipunadi Hettiarachchi
  14. Davina Calbraith
  15. Noshin Sajedi
  16. Iain Milligan
  17. Yrene Themistocleous
  18. Diane Corrigan
  19. Lisa Cromey
  20. Lesley Price
  21. Sally Stewart
  22. Elen de Lacy
  23. Chris Norman
  24. Ezra Linley
  25. Ashley David Otter
  26. Amanda Semper
  27. Jacqueline Hewson
  28. Silvia D’Arcangelo
  29. the SIREN Study Group
  30. Meera Chand
  31. Colin S Brown
  32. Tim Brooks
  33. Jasmin Islam
  34. Andre Charlett
  35. Susan Hopkins

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Abstract

Background

Understanding the duration and effectiveness of infection and vaccine-acquired SARS-CoV-2 immunity is essential to inform pandemic policy interventions, including the timing of vaccine-boosters. We investigated this in our large prospective cohort of UK healthcare workers undergoing routine asymptomatic PCR testing.

Methods

We assessed vaccine effectiveness (VE) (up to 10-months after first dose) and infection-acquired immunity by comparing time to PCR-confirmed infection in vaccinated and unvaccinated individuals using a Cox regression-model, adjusted by prior SARS-CoV-2 infection status, vaccine-manufacturer/dosing-interval, demographics and workplace exposures.

Results

Of 35,768 participants, 27% (n=9,488) had a prior SARS-CoV-2 infection. Vaccine coverage was high: 97% had two-doses (79% BNT162b2 long-interval, 8% BNT162b2 short-interval, 8% ChAdOx1). There were 2,747 primary infections and 210 reinfections between 07/12/2020 and 21/09/2021. Adjusted VE (aVE) decreased from 81% (95% CI 68%-89%) 14-73 days after dose-2 to 46% (95% CI 22%-63%) >6-months; with no significant difference for short-interval BNT162b2 but significantly lower aVE (50% (95% CI 18%-70%) 14-73 days after dose-2 from ChAdOx1. Protection from infection-acquired immunity showed evidence of waning in unvaccinated follow-up but remained consistently over 90% in those who received two doses of vaccine, even in those infected over 15-months ago.

Conclusion

Two doses of BNT162b2 vaccination induce high short-term protection to SARS-CoV-2 infection, which wanes significantly after six months. Infection-acquired immunity boosted with vaccination remains high over a year after infection. Boosters will be essential to maintain protection in vaccinees who have not had primary infection to reduce infection and transmission in this population.

Trial registration number

ISRCTN11041050

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.11.29.21267006: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: This study was registered, number ISRCTN11041050, and received approval from the Berkshire Research Ethics Committee on 22 May 2020.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    5 We used STATA software (version 15.1; StataCorp LLC, College Station, TX, USA) for all analyses.
    STATA
    suggested: (Stata, RRID:SCR_012763)
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The most important limitation of our study is the relatively small number of participants continuing to contribute follow-up time to key vaccination exposures: unvaccinated, ChAdOx1 and BNT162b2 short interval. This particularly affects the precision of estimates and our ability to assess potential waning following two-doses of ChAdOx1, and >15 months after primary infection in unvaccinated participants. We consider that the strengths of our study design and speed of vaccine deployment significantly limit the impact of depletion-of-susceptible bias (which particularly affects studies on vaccine-waning),19 however we recognise some residual confounding may remain.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    ISRCTN11041050NANA

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.11.29.21267006v1 on medRxiv