Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination

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Abstract

SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have immunologically assessed serial Omicron infections. We characterized SARS-CoV-2 humoral responses in an individual who acquired laboratory-confirmed Omicron BA.1.15 ten weeks after a third dose of BNT162b2, and BA.2 thirteen weeks later. Responses were compared to 124 COVID-19-naive vaccinees. One month post-second and -third vaccine doses, the participant’s wild-type and BA.1-specific IgG, ACE2-displacement and virus neutralization activities were average for a COVID-19-naive triple-vaccinated individual. BA.1 infection boosted the participant’s responses to the cohort ≥95th percentile, but even this strong “hybrid” immunity failed to protect against BA.2. Reinfection increased BA.1 and BA.2-specific responses only modestly. Though vaccines clearly protect against severe disease, results highlight the continued importance of maintaining additional protective measures to counteract the immune-evasive Omicron variant, particularly as vaccine-induced immune responses naturally decline over time.

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  1. SciScore for 10.1101/2022.05.19.22275026: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Ethics approval: All participants provided written informed consent.
    IRB: This study was approved by the University of British Columbia/Providence Health Care and Simon Fraser University Research Ethics Boards (protocol H20-03906).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    At each visit, serum was tested for the presence of SARS-CoV-2 anti-nucleocapsid (N) antibodies, which indicate seroconversion following infection, using the Elecsys Anti-SARS-CoV-2 assay on a Cobas e601 module analyzer (Roche Diagnostics).
    anti-nucleocapsid (N)
    suggested: None
    Binding antibody assays: We quantified anti-Spike Receptor Binding Domain (RBD) binding IgG concentrations in serum using the V-plex SARS-CoV-2 (IgG) Panel 22 ELISA kit (Meso Scale Diagnostics), which features wild-type and Omicron BA.1 RBD antigens.
    anti-Spike Receptor Binding Domain (RBD
    suggested: None
    SARS-CoV-2 (IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Data visualization and statistical analysis was conducted in Prism v9.2.0 (GraphPad).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    A limitation of our study is that it did not assess T cell responses, which can reduce disease severity but may have less impact on virus transmission (53, 54), and thus we may be underestimating the protection that results from infection and reinfection in this case. Indeed, the participant’s symptoms following both infections were not severe enough to require hospitalization, demonstrating that vaccination was effective in its primary goal of preventing disease. Our results nevertheless illustrate the potentially limited ability of current vaccines to prevent recurrent infections and symptomatic disease caused by Omicron variants.

    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.
    • No funding statement was detected.
    • 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.