Relative infectiousness of SARS-CoV-2 vaccine breakthrough infections, reinfections, and primary infections

  1. Laith J. Abu-Raddad
  2. Hiam Chemaitelly
  3. Houssein H. Ayoub
  4. Patrick Tang
  5. Peter Coyle
  6. Mohammad R. Hasan
  7. Hadi M. Yassine
  8. Fatiha M. Benslimane
  9. Hebah A. Al-Khatib
  10. Zaina Al-Kanaani
  11. Einas Al-Kuwari
  12. Andrew Jeremijenko
  13. Anvar Hassan Kaleeckal
  14. Ali Nizar Latif
  15. Riyazuddin Mohammad Shaik
  16. Hanan F. Abdul-Rahim
  17. Gheyath K. Nasrallah
  18. Mohamed Ghaith Al-Kuwari
  19. Adeel A. Butt
  20. Hamad Eid Al-Romaihi
  21. Abdullatif Al-Khal
  22. Mohametabd H. Al-Thani
  23. Roberto Bertollini

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Abstract

SARS-CoV-2 breakthrough infections in vaccinated individuals and in those who had a prior infection have been observed globally, but the transmission potential of these infections is unknown. The RT-qPCR cycle threshold (Ct) value is inversely correlated with viral load and culturable virus. Here, we investigate differences in RT-qPCR Ct values across Qatar’s national cohorts of primary infections, reinfections, BNT162b2 (Pfizer-BioNTech) breakthrough infections, and mRNA-1273 (Moderna) breakthrough infections. Our matched-cohort analyses of the randomly diagnosed infections show higher mean Ct value in all cohorts of breakthrough infections compared to the cohort of primary infections in unvaccinated individuals. The Ct value is 1.3 (95% CI: 0.9–1.8) cycles higher for BNT162b2 breakthrough infections, 3.2 (95% CI: 1.9–4.5) cycles higher for mRNA-1273 breakthrough infections, and 4.0 (95% CI: 3.5–4.5) cycles higher for reinfections in unvaccinated individuals. Since Ct value correlates inversely with SARS-CoV-2 infectiousness, these differences imply that vaccine breakthrough infections and reinfections are less infectious than primary infections in unvaccinated individuals. Public health benefits of vaccination may have been underestimated, as COVID-19 vaccines not only protect against acquisition of infection, but also appear to protect against transmission of infection.

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  1. Version published to 10.1038/s41467-022-28199-7
  2. ScreenIT

    SciScore for 10.1101/2021.07.28.21261086: (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.
    RandomizationEvery real time reverse transcription-PCR (RT-qPCR) test conducted in Qatar, regardless of location (outpatient clinic, drive-thru, or hospital, etc.), is classified on the basis of symptoms and the reason for testing (clinical symptoms, contact tracing, random testing campaigns (surveys), individual requests, routine healthcare testing, pre-travel, and port of entry).
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were conducted in STATA/SE version 17.047.
    STATA/SE
    suggested: None

    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 has limitations. The number of documented mRNA-1273 breakthrough infections was small, thereby limiting the statistical precision of the comparisons involving these infections, leading to estimates with wider 95% confidence intervals, and perhaps making them more prone to bias. The study was implemented on documented infections, but other infections may have occurred and gone undocumented. It is possible that breakthrough infections in those vaccinated or who had a prior infection are less likely to be documented, perhaps because of minimal/mild or no symptoms. However, with the high rate of PCR testing in Qatar, the majority of infections are identified not because of testing symptomatic cases, but because of testing for other reasons, such as random testing campaigns, contact tracing, individual requests, routine healthcare testing, pre-travel, and at ports of entry. The results of our study were also consistent when we included only the randomly diagnosed infections. Imperfect assay sensitivity and specificity of RT-qPCR testing may have affected infection ascertainment, but RT-qPCR testing was performed using a validated commercial platform that has been used globally and has essentially 100% sensitivity and specificity26 (Methods). While it is established that SARS-CoV-2 viral load strongly correlates with culturable virus10 and infectiousness, the exact mathematical relationship linking viral load to infectiousness is not known. Therefore, we generated estima...

    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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  3. Version published to 10.1101/2021.07.28.21261086v1 on medRxiv