Delta variant and mRNA Covid-19 vaccines effectiveness: higher odds of vaccine infection breakthroughs

  1. Irina Kislaya
  2. Eduardo Freire Rodrigues
  3. Vítor Borges
  4. João Paulo Gomes
  5. Carlos Sousa
  6. José Pedro Almeida
  7. André Peralta-Santos
  8. Baltazar Nunes

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Abstract

Background

The SARS-CoV-2 Delta variant (B.1.617.2), initially identified in India, has become predominant in several countries, including Portugal. Few studies have compared the effectiveness of mRNA vaccines against Delta versus Alpha variant of concern (VOC) and estimated variant-specific viral loads in vaccine infection breakthroughs cases. In the context of Delta dominance, this information is critical to inform decision-makers regarding the planning of restrictions and vaccination roll-out.

Methods

We developed a case-case study to compare mRNA vaccines’ effectiveness against Delta (B.1.617.2) versus Alpha (B.1.1.7) variants. We used RT-PCR positive cases notified to the National Surveillance System between 17th of May and 4th of July 2021 (week 20 to 26) and information about demographics and vaccination status through the electronic vaccination register. Whole-genome sequencing (WGS) or spike (S) gene target failure (SGTF) data were used to classify SARS-CoV-2 variants. The odds of vaccinated individuals to become infected (odds of vaccine infection breakthrough) in Delta cases compared to Alpha SARS-CoV-2 cases was estimated by conditional logistic regression adjusted for age group, sex, and matched by the week of diagnosis. As a surrogate of viral load, mean RT-PCR Ct values were stratified and compared between vaccine status and VOC.

Results

Of the 2 097 SARS-CoV-2 RT-PCR positive cases included in the analysis, 966 (46.1%) were classified with WGS and 1131 (53.9%) with SGTF. Individuals infected with the Delta variant were more frequently vaccinated 162 (12%) than individuals infected with the Alpha variant 38 (5%). We report a statistically significant higher odds of vaccine infection breakthrough for partial (OR=1.70; CI95% 1.18 to 2.47) and complete vaccination (OR=1.96; CI95% 1.22 to 3.14) in the Delta cases when compared to the Alpha cases, suggesting lower mRNA vaccine effectiveness against Delta cases. On our secondary analysis, we observed lower mean Ct values for the Delta VOC cases versus Alpha, regardless the vaccination status. Additionally, the Delta variant cases revealed a Ct-value mean increase of 2.24 (CI95% 0.85 to 3.64) between unvaccinated and fully vaccinated breakthrough cases contrasting with 4.49 (CI95% 2.07 to 6.91) in the Alpha VOC, suggesting a lower impact of vaccine on viral load of Delta cases.

Conclusions

We found significantly higher odds of vaccine infection breakthrough in Delta cases when compared to Alpha cases, suggesting lower effectiveness of the mRNA vaccines in preventing infection with the Delta variant. Additionally, the vaccine breakthrough cases are estimated to be of higher mean Ct values, suggesting higher infectiousness with the Delta variant infection. These findings can help decision-makers weigh on the application or lifting of control measures and adjusting vaccine roll-out depending on the predominance of the Delta variant and the coverage of partial and complete mRNA vaccination.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Lindsay Keegan, Jay Love

    Review 2: "Delta variant and mRNA Covid-19 vaccines effectiveness: higher odds of vaccine infection breakthroughs"

    This preprint claims that, compared to Alpha, Delta cases have higher odds of vaccine breakthrough infections and lower mean Ct values. Although reviewers agree on the timeliness of this paper, they had concerns with the statistical methods used to get to the conclusions.

  2. Rapid Reviews Infectious Diseases

    Timothy Farinholt

    Review 1: "Delta variant and mRNA Covid-19 vaccines effectiveness: higher odds of vaccine infection breakthroughs"

    This preprint claims that, compared to Alpha, Delta cases have higher odds of vaccine breakthrough infections and lower mean Ct values. Although reviewers agree on the timeliness of this paper, they had concerns with the statistical methods used to get to the conclusions.

  4. ScreenIT

    SciScore for 10.1101/2021.08.14.21262020: (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.
    RandomizationFor this study, each notifying laboratory selected a random sample of PCR-positive nasopharyngeal samples collected between the 17th of May and the 4th of July 2021 (respectively, week 20 and week 26) to be sent to the National SARS-CoV-2 Genomic Surveillance Network [1,13] and, thus, to be included in the study.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Additionally, to assess the bias of misclassification error associated with the SGTF method — particularly in the early weeks of the study period where the overall prevalence of the Delta variant was lower, and possibly SGTF sensitivity was also lower — we analyzed samples identified exclusively through WGS during weeks 22-26.
    WGS
    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, however, limitations. We report odds of vaccine breakthrough between Delta and Alpha VOC, which can be interpreted as a measure of the relative vaccine effectiveness. Although a case-case study design does not provide a direct measure of effectiveness against a specific VOC, it may provide substantial evidence for further public health measures to control the transmission of SARS-CoV-2 in the context of the global lifting of restrictions. Our results include infected individuals (both asymptomatic and symptomatic) and thus cannot estimate effectiveness against symptomatic disease. However, by restricting our main analysis to samples with higher viral loads — selected based on low Ct values (Ct<25) — an even higher OR of vaccination between Delta and Alpha variant was obtained which supports the relevance of the Delta relative vaccine effectiveness reduction effect in the transmission of SARS-CoV-2, both for partial (OR=2.47; CI95%: 1.48 to 4.12) and complete vaccination (OR= 2.42; CI95% 1.06 to 5.51). On our secondary analysis, we observed lower Ct values — indicative of higher viral loads — among Delta cases compared to Alpha after both complete (MD=-2.24; CI95% -4.8 to 0.32) and partial vaccination (MD=–1.88; CI95% -3.77 to 0.003). Furthermore, while complete vaccination increases Ct values (thus reducing estimated viral loads) on Alpha cases by 4.49 (CI95% 2.07 to 6.91), with the Delta variant case complete vaccination had a much discrete increase of Ct val...

    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 10.1101/2021.08.14.21262020v1 on medRxiv