Waning of mRNA-1273 vaccine effectiveness against SARS-CoV-2 infection in Qatar

  1. Laith J. Abu-Raddad
  2. Hiam Chemaitelly
  3. Houssein H. Ayoub
  4. Hadi M. Yassine
  5. Fatiha M. Benslimane
  6. Hebah A. Al Khatib
  7. Patrick Tang
  8. Mohammad R. Hasan
  9. Peter Coyle
  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. Mohamed H. Al-Thani
  22. Abdullatif Al Khal
  23. Roberto Bertollini

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Abstract

BACKGROUND

In early 2021, Qatar launched a mass immunization campaign with Moderna’s mRNA-1273 COVID-19 vaccine. We assessed persistence of real-world mRNA-1273 effectiveness against SARS-CoV-2 infection and against COVID-19 hospitalization and death.

METHODS

Effectiveness was estimated using test-negative, case-control study design, between January 1 and December 5, 2021. Effectiveness was estimated against documented infection (a PCR-positive swab, regardless symptoms), and against any severe (acute-care hospitalization), critical (ICU hospitalization), or fatal COVID-19.

RESULTS

By December 5, 2021, 2,962 breakthrough infections had been recorded among those who received two mRNA-1273 doses. Of these infections, 19 progressed to severe COVID-19 and 4 to critical, but none to fatal disease. mRNA-1273 effectiveness against infection was negligible for the first two weeks after the first dose, increased to 65.5% (95% CI: 62.7-68.0%) 14 or more days after the first dose, and reached its peak at about 90% in the first three months after the second dose. Effectiveness declined gradually starting from the fourth month after the second dose and was below 50% by the 7 th month after the second dose. Effectiveness against severe, critical, or fatal COVID-19 reached its peak at essentially 100% right after the second dose, and there was no evidence for declining effectiveness over time. Effectiveness against symptomatic versus asymptomatic infection demonstrated the same pattern of waning, but effectiveness against symptomatic infection was consistently higher than that against asymptomatic infection and waned more slowly.

CONCLUSIONS

mRNA-1273-induced protection against infection appears to wane month by month after the second dose. Meanwhile, protection against hospitalization and death appears robust with no evidence for waning for several months after the second dose.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.12.16.21267902: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards with a waiver of informed consent.
    Consent: The study was approved by the Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards with a waiver of informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot 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:
    Notwithstanding these limitations, consistent findings were reached, indicating a large effect size for the waning of vaccine protection over time, regardless of the reason for PCR testing, and regardless of the presence or absence of symptoms. Moreover, with the mass scale of PCR testing in Qatar,3 the likelihood of bias is perhaps minimized. Extensive sensitivity and additional analyses were conducted to investigate effects of potential bias in our recent study for the BNT162b2 vaccine,3 which used the same methodology as the present study. All analyses presented consistent findings of waning vaccine protection.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.12.16.21267902 on medRxiv
  3. Version published to 10.1056/nejmoa2114114
  4. ScreenIT

    SciScore for 10.1101/2021.08.25.21262584: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was approved by the Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards with waiver of informed consent.
    Consent: The study was approved by the Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards with waiver of informed consent.
    Sex as a biological variablenot detected.
    RandomizationEvery PCR test conducted in Qatar, regardless of location or setting, 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 at port of entry).
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: To provide further validation of study results, effectiveness was further estimated by deriving adjusted odds ratios (AORs) from multivariable logistic regression analyses of associations with a PCR-positive test, using the full unmatched sample, that is, by applying a different method from that of the main analysis of matched test-negative, case-control study design.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were conducted in STATA/SE version 17.0.28
    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. Data on co-morbid conditions were not available; therefore, they could not be explicitly factored into our analysis. However, adjusting for age may have served as a proxy given that co-morbidities are associated with older age. With the young population of Qatar,11, 12 only a small proportion of the study population may have had serious co-morbid conditions. Our findings may not be generalizable to other countries where the elderly constitute a sizable proportion of the total population. Effectiveness was assessed using an observational, test-negative, case-control study design,14, 15 rather than a randomized, clinical trial design, in which cohorts of vaccinated and unvaccinated individuals were followed up. We have been unable to use a cohort study design due to depletion of the unvaccinated cohorts with the high vaccine coverage. However, the cohort study design applied earlier to the same population of Qatar, yielded similar findings to the test-negative case-control design,2, 4 supporting the validity of this standard approach in assessing vaccine effectiveness for respiratory tract infections.2, 4, 14–18 The results of this study are also consistent with our earlier effectiveness estimates immediately after the first and second doses,2, 29 noting that the earlier estimates were against (mostly) symptomatic infections with low PCR cycle threshold values, while the present study estimates are against (mostly) asymptomatic infections of both hig...

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  5. Version published to 10.1101/2021.08.25.21262584 on medRxiv