Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK

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Abstract

The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is reduced with the B.1.617.2 variant (absolute difference of 10–13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher in vaccinated individuals after a prior infection and in younger adults. With B.1.617.2, infections occurring after two vaccinations had similar peak viral burden as those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with B.1.617.2.

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  1. SciScore for 10.1101/2021.08.18.21262237: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study received ethical approval from the South Central Berkshire B Research Ethics Committee (20/SC/0195)
    Consent: Following verbal agreement to participate, a study worker visited each selected household to take written informed consent for individuals aged 2 years and over.
    Sex as a biological variablenot detected.
    RandomizationPrivate households are randomly selected on a continuous basis from address lists and previous surveys to provide a representative sample across the UK.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Blood samples were couriered directly to the University of Oxford, where they were tested for the SARS-CoV-2 antibody using an ELISA detecting anti-trimeric spike IgG38.
    anti-trimeric spike IgG38
    suggested: None
    Software and Algorithms
    SentencesResources
    After this, it used a commercialised CE-marked version of the assay, the Thermo Fisher OmniPATH 384 Combi SARS-CoV-2 IgG ELISA (Thermo Fisher Scientific, Waltham, MA, USA), with the same antigen and a colorimetric detection system (positivity threshold 42 ng/ml monoclonal antibody unit equivalents, determined from 3840 samples run in parallel).
    Thermo Fisher OmniPATH
    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:
    Our study has several limitations. While we have included a broad set of potential confounders, results may still be biased by unknown confounders or misclassification of prior infection status, for example due only having antibody measurements on a subset. Participants are tested initially at weekly and then monthly visits, meaning when rates are increasing, as when Delta came to dominate, we expect to identify infected individuals earlier in their infection episode36,37, as shown and adjusted for in our Ct analysis. Late detection of older infections on the fixed visit schedule means some positives could be classified as having occurred shortly after vaccination while the infection may actually have been acquired before vaccination, potentially diluting vaccine effectiveness estimates. However most infections ≥14d post second vaccination had a preceding negative after second vaccination. To avoid misclassification bias from erroneously classifying higher Ct positives where only ORF1ab+N genes were detected as Alpha, our comparisons treated calendar periods as an instrumental variable, according to whether Alpha or Delta was dominant, but this will likely lead to a small amount of bias in our vaccine effectiveness estimates. In summary, with Delta, BNT162b2 and ChAdOx1 remain protective against any new PCR-positive and infections with higher viral burden or symptoms, but vaccine effectiveness is reduced, with evidence of significantly different dynamics of immunity against i...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    ISRCTN21086382NANA


    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.