Investigating SARS-CoV-2 breakthrough infections per variant and vaccine type

  1. Jozef Dingemans
  2. Brian M. J. W. van der Veer
  3. Koen M. F. Gorgels
  4. Volker Hackert
  5. Casper D. J. den Heijer
  6. Christian J. P. A Hoebe
  7. Paul H. M. Savelkoul
  8. Lieke B. van Alphen

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Abstract

Breakthrough SARS-CoV-2 infections have been reported in fully vaccinated individuals, in spite of the high efficacy of the currently available vaccines, proven in trials and real-world studies. Several variants of concern (VOC) have been proffered to be associated with breakthrough infections following immunization. In this study, we investigated 378 breakthrough infections recorded between January and July 2021 and compared the distribution of SARS-CoV-2 genotypes identified in 225 fully vaccinated individuals to the frequency of circulating community lineages in the region of South Limburg (The Netherlands) in a week-by-week comparison. Although the proportion of breakthrough infections was relatively low and stable when the Alpha variant was predominant, the rapid emergence of the Delta variant lead to a strong increase in breakthrough infections, with a higher relative proportion of individuals vaccinated with Vaxzevria or Jcovden being infected compared to those immunized with mRNA-based vaccines. A significant difference in median age was observed when comparing fully vaccinated individuals with severe symptoms (83 years) to asymptomatic cases (46.5 years) or individuals with mild-to-moderate symptoms (42 years). There was no association between SARS-CoV-2 genotype or vaccine type and disease symptoms. Furthermore, the majority of adaptive mutations were concentrated in the N-terminal domain of the Spike protein, highlighting its role in immune evasion. Interestingly, symptomatic individuals harbored significantly higher SARS-CoV-2 loads than asymptomatic vaccinated individuals and breakthrough infections caused by the Delta variant were associated with increased viral loads compared to those caused by the Alpha variant. In addition, we investigated the role of the Omicron variant in causing breakthrough infections by analyzing 135 samples that were randomly selected for genomic surveillance during the transition period from Delta to Omicron. We found that the proportion of Omicron vs. Delta infections was significantly higher in individuals who received a booster vaccine compared to both unvaccinated and fully vaccinated individuals. Altogether, these results indicate that the emergence of the Delta variant and in particular Omicron has lowered the efficiency of particular vaccine types to prevent SARS-CoV-2 infections and that, although rare, the elderly are particularly at risk of becoming severely infected as the consequence of a breakthrough infection.

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  1. Version published to 10.3389/fmicb.2022.1027271
  2. ScreenIT

    SciScore for 10.1101/2021.11.22.21266676: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The Medical Review Ethics Committee of the Maastricht UMC+ confirmed that the Medical Research Involving Human Subjects Act (WMO) does not apply to the above mentioned study and that an official approval of this study by the committee is not required (METC reference number 2021-2838).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis: All statistical analyses were performed using GraphPad Prism 9.0.0 software (GraphPad, La Jolla, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Limitations were the fact that the number of reported breakthrough infections are an underestimation of the effective number, due to asymptomatic or mild cases or because of severe cases in local hospitals that were not reported to the regional public health service. Furthermore, asymptomatic cases were only followed up for a limited amount of time, possibly leading to the underestimation of symptomatic cases. Thirdly, only samples from cases with sufficiently high viral loads could be sequenced (

    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.

    About SciScore

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  3. Version published to 10.1101/2021.11.22.21266676v1 on medRxiv