Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529) dominance: A Danish nationwide study

  1. Katrine Finderup Nielsen
  2. Ida Rask Moustsen-Helms
  3. Astrid Blicher Schelde
  4. Mie Agermose Gram
  5. Hanne-Dorthe Emborg
  6. Jens Nielsen
  7. Christian Holm Hansen
  8. Michael Asger Andersen
  9. Marianna Meaidi
  10. Jan Wohlfahrt
  11. Palle Valentiner-Branth

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Abstract

Introduction

Individuals with a prior severe acute respiratory corona virus 2 (SARS-CoV-2) infection have a moderate to high degree of protection against reinfection, though seemingly less so when the Omicron variant of SARS-CoV-2 started to circulate. The aim of this study was to evaluate the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, that is, in individuals with prior SARS-CoV-2 infection, during periods with different dominant SARS-CoV-2 variants.

Methods

A nationwide cohort study design including all individuals with a confirmed SARS-CoV-2 infection, who were alive and residing in Denmark between 1 January 2020 and 31 January 2022 were used. Using Danish nationwide registries, we obtained information on SARS-CoV-2 infections, Coronavirus Disease 2019 (COVID-19) vaccination, age, sex, comorbidity, staying at hospital and region of affiliation. The study population included were individuals with prior SARS-CoV-2 infection. Crude and adjusted estimates of VE against SARS-CoV-2 reinfection with 95% confidence intervals (CIs) were calculated using Poisson and Cox regression models, respectively. The VE estimates were calculated separately for three periods with different dominant SARS-CoV-2 variants (Alpha (B.1.1.7), Delta (B.1.617.2), or Omicron (B.1.1.529)) and by time since vaccination using unvaccinated as the reference.

Findings

The study population comprised of 209,814 individuals infected before or during the Alpha period, 292,978 before or during the Delta period and 245,530 before or during the Omicron period. Of these, 40,281 individuals had completed their primary vaccination series during the Alpha period (19.2%), 190,026 during the Delta period (64.9%) and 158,563 during the Omicron period (64.6%). VE against reinfection following any COVID-19 vaccine type administered in Denmark, peaked at 85% (95% CI: 37% to 97%) at 104 days or more after vaccination during the Alpha period, 88% (95% CI: 81% to 92%) 14-43 days after vaccination during the Delta period and 60% (95% CI: 58% to 62%) 14-43 days after vaccination during the Omicron period. Waning immunity was observed, and was most pronounced during the Omicron period.

Interpretation

This study shows that, in previously infected individuals, completing a primary vaccination series was associated with a significant protection against SARS-CoV-2 reinfection compared with no vaccination for all three variant periods. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods.

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    SciScore for 10.1101/2022.06.01.22275858: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study also has some limitations. Despite the high test rate, we cannot rule out undetected reinfections, especially asymptomatic infections among vaccinated individuals, which might inflate the VE. We also cannot rule out that vaccinated and unvaccinated individuals had different health seeking behavior or risk behavior, which could affect VE. Additionally, from April 2021, a corona pass was introduced in Denmark and a valid corona pass gained by previous infection or vaccination, was required for a broad range of social activities, including restaurants, gyms etc.. This may have affected test activity differently for unvaccinated and vaccinated individuals. However, this was common practice during both the Delta and Omicron period and might therefore not play a role when considering VE in these periods. In summary, this study showed that among previously infected individuals who have completed a primary vaccination series, there is a significant VE against SARS-CoV-2 reinfection for the SARS-CoV- 2 variants Alpha, Delta and Omicron; lasting up to 9 months. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

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  2. Version published to 10.1101/2022.06.01.22275858v1 on medRxiv