Anti-spike antibody response to natural SARS-CoV-2 infection in the general population

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Abstract

Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection and risk of reinfection, however large-scale representative studies are limited. Here we estimated antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as ‘non-responders’ not developing anti-spike antibodies, who were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. These estimates could inform planning for vaccination booster strategies.

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  1. SciScore for 10.1101/2021.07.02.21259897: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 antibody levels were tested on venous or capillary blood samples using an ELISA detecting anti-trimeric spike IgG developed by the University of Oxford34,46.
    anti-trimeric spike IgG
    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), with the same antigen and colorimetric detection.
    Thermo Fisher OmniPATH
    suggested: None

    Results from OddPub: Thank you for sharing your code.


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Study limitations include the fact that we only measured anti-spike IgG using a single assay; seronegative non-responders in Class 3 might have antibodies detected using other assays or other target antigens. We did not measure neutralizing antibodies or T cell responses; however, neutralizing antibody responses are strongly correlated (Spearman ρ=0.87) with anti-spike binding antibodies following infection as previously reported45. This community survey had visits scheduled independent of infection or symptom status, so we could not precisely identify the start of infection or symptom onset; we therefore also incorporated positives from the national testing programme (targeting symptomatic infections) and used the first swab positive test and latent class models to indirectly estimate the start of infection. Similarly, we were not able to model antibody trajectories from each participant’s maximum levels since antibody data were collected monthly. However, we chose a starting point that was close to but slightly after the peak IgG level; while this could slightly underestimate peak IgG levels, the half-life will be unbiasedly estimated if the assumption of exponential decline is correct. Re-infections were rare, with only 92 (0.5%) participants with antibody data having potential re-infections >120 days after their first infection episode (Figure S1). Most had only one antibody result, so it was impossible to investigate any boosting of antibody levels following re-infection...

    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.


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