Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: a cohort study from OpenSAFELY

  1. The OpenSAFELY Collaborative
  2. Amelia Green
  3. Helen Curtis
  4. William Hulme
  5. Elizabeth Williamson
  6. Helen McDonald
  7. Krishnan Bhaskaran
  8. Christopher Rentsch
  9. Anna Schultze
  10. Brian MacKenna
  11. Viyaasan Mahalingasivam
  12. Laurie Tomlinson
  13. Alex Walker
  14. Louis Fisher
  15. Jon Massey
  16. Colm Andrews
  17. Lisa Hopcroft
  18. Caroline Morton
  19. Richard Croker
  20. Jessica Morley
  21. Amir Mehrkar
  22. Seb Bacon
  23. David Evans
  24. Peter Inglesby
  25. George Hickman
  26. Tom Ward
  27. Simon Davy
  28. Rohini Mathur
  29. John Tazare
  30. Rosalind Eggo
  31. Kevin Wing
  32. Angel Wong
  33. Harriet Forbes
  34. Chris Bates
  35. Jonathan Cockburn
  36. John Parry
  37. Frank Hester
  38. Sam Harper
  39. Ian Douglas
  40. Stephen Evans
  41. Liam Smeeth
  42. Ben Goldacre

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Abstract

Background

While the vaccines against COVID-19 are highly effective, COVID-19 vaccine breakthrough is possible despite being fully vaccinated. With SARS-CoV-2 variants still circulating, describing the characteristics of individuals who have experienced COVID-19 vaccine breakthroughs could be hugely important in helping to determine who may be at greatest risk.

Methods

With the approval of NHS England, we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY-TPP database of fully vaccinated individuals, linked to secondary care and death registry data and described the characteristics of those experiencing COVID-19 vaccine breakthroughs.

Results

As of 1st November 2021, a total of 15,501,550 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: ​107–179). From within this population, a total of 579,780 (<4%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate (IR) was 98.06 (95% CI 97.93–98.19). There were 28,580 COVID-19-related hospital admissions, 1980 COVID-19-related critical care admissions and 6435 COVID-19-related deaths; corresponding IRs 4.77 (95% CI 4.74–4.80), 0.33 (95% CI 0.32–0.34) and 1.07 (95% CI 1.06–1.09), respectively. The highest rates of breakthrough COVID-19 were seen in those in care homes and in patients with chronic kidney disease, dialysis, transplant, haematological malignancy or who were immunocompromised.

Conclusions

While the majority of COVID-19 vaccine breakthrough cases in England were mild, some differences in rates of breakthrough cases have been identified in several clinical groups. While it is important to note that these findings are simply descriptive and cannot be used to answer why certain groups have higher rates of COVID-19 breakthrough than others, the emergence of the Omicron variant of COVID-19 coupled with the number of positive SARS-CoV-2 tests still occurring is concerning and as numbers of fully vaccinated (and boosted) individuals increases and as follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, to assess vaccine waning and rates of breakthrough COVID-19 between different variants, aimed at identifying individuals at higher risk, are needed.

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  1. Version published to 10.1186/s12916-022-02422-0
  2. Version published to 10.1101/2021.11.08.21265380v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.11.08.21265380: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Software and Reproducibility: Data management and analysis was performed using the OpenSAFELY software libraries, Python 3 and R version 4.0.2.
    Python
    suggested: (IPython, RRID:SCR_001658)

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

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and weaknesses: This study used large-scale, routinely-collected primary care records, linked to coronavirus testing surveillance, hospital, and death registry data. This allowed us to describe a substantial proportion of the English population in rich longitudinal detail and to detect variations in COVID-19 vaccine breakthrough cases, as early as possible. We acknowledge several important limitations of these findings. First, even though the base population consisted of over 10 million fully vaccinated individuals the numbers of COVID-19 vaccine breakthrough cases were relatively small, especially for hospitalisations and deaths. This made comparisons between outcomes, specifically at selected clinical and demographic levels difficult,meaning rates could be imprecisely estimated. Second, due to the targeted roll out of the COVID-19 vaccination programme in England, this cohort represents mostly older and vulnerable populations. In addition, follow-up time is systematically different amongst individuals included in this study and no adjustment for this has been made. Third, asymptomatic testing patterns vary between individuals. Apart from health and care workers, asymptomatic individuals without any underlying health issues or comorbidities are less likely to get tested than those with underlying health issues or comorbidities (i.e., haemodialysis patients) who will undergo asymptomatic testing regularly. Most lateral flow tests conducted at home are not included i...

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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

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  4. Version published to 10.1101/2021.11.08.21265380v1 on medRxiv