Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

  1. Talia Kustin
  2. Noam Harel
  3. Uriah Finkel
  4. Shay Perchik
  5. Sheri Harari
  6. Maayan Tahor
  7. Itamar Caspi
  8. Rachel Levy
  9. Michael Leshchinsky
  10. Shifra Ken Dror
  11. Galit Bergerzon
  12. Hala Gadban
  13. Faten Gadban
  14. Eti Eliassian
  15. Orit Shimron
  16. Loulou Saleh
  17. Haim Ben-Zvi
  18. Elena Keren Taraday
  19. Doron Amichay
  20. Anat Ben-Dor
  21. Dana Sagas
  22. Merav Strauss
  23. Yonat Shemer Avni
  24. Amit Huppert
  25. Eldad Kepten
  26. Ran D. Balicer
  27. Doron Netzer
  28. Shay Ben-Shachar
  29. Adi Stern

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Abstract

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.

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  1. Version published to 10.1038/s41591-021-01413-7
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    SciScore for 10.1101/2021.04.06.21254882: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics statement: The study was approved by the CHS institutional review board (IRB #0016-21-COM2) and was exempt from the requirement for informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    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:
    Additionally, sequencing limitations prevented us from sequencing very low viral load samples (Methods), and thus the focus of our study was on vaccinees who generated higher viral loads. However, it has been shown that cases with low viral load may be a lesser concern from a public health perspective, as they are associated with less symptoms and decreased transmission [16]. Finally, our FE cohort is based on infections documented seven or more days post the second vaccine dose (Table 1). Some subjects in this cohort may have been infected before the immunity from the boost was fully established, and it is thus possible that enhanced immunity from the boost, which develops over time [17], may more effectively prevent infection with the B.1.351 variant. Further research is required to test whether and how these potential limitations affect the results. The main caveat of our study was the small sample size of both the WT and B.1.351 variants. These small samples sizes are a product of (a) the dramatic increase in frequency of the B.1.1.7 variant (first detected in Israel in mid-December 2020) (Fig. 1A), and (b) the low frequency of the B.1.351 variant in Israel [14]. In fact, in our latest samples obtained in late February and early March 2021, we noted fixation of the B.1.1.7 variant, but this interpretation requires caution as our sample size was low (Fig. 1A). Furthermore, caution is required from over-interpreting the odds ratios obtained, as the absolute numbers we found...

    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.

    About SciScore

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  8. Version published to 10.1101/2021.04.06.21254882 on medRxiv