Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors

This article has been Reviewed by the following groups

Read the full article See related articles

Abstract

The novel SARS-CoV-2 virus emerged in late 2019 and has caused a global health and economic crisis. The characterization of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes as well for treatment options such as transfusion with convalescent plasma or immunoglobin products derived from convalescent plasma. In this study, we measured antibody responses in 844 longitudinal samples from 151 RT-PCR positive SARS-CoV-2 convalescent adults during the first 34 weeks after onset of symptoms. All donors were seropositive at the first sampling moment and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels slowly declined with median half-life’s of 62 and 59 days during 2-5 months after symptom onset, respectively. The rate of decline of antibody levels diminished during extended follow-up. In addition, the magnitude of the IgG response correlated with neutralization capacity measured in a classic plaque reduction assay as well in our in-house developed competition assay. The result of this study gives valuable insight into the longitudinal response of antibodies to SARS-CoV-2.

Article activity feed

  1. SciScore for 10.1101/2021.01.06.20249035: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Data and samples were collected only from voluntary, non-remunerated, adult donors as described previously [27], and who provided written informed consent as part of routine donor selection and blood collection procedures, that were approved by the Ethics Advisory Council of Sanquin Blood Supply Foundation.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For anti-RBD IgG1 and IgG3, the calibrator consisted of recombinantly expressed IgG1 and IgG3 monoclonal antibody.
    anti-RBD IgG1
    suggested: None
    IgG3
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The ACE2 was produced in HEK cells with a HAVT20 leader peptide, 10xhis-tag and a BirA-tag as described by Dekkers et al., [28].
    HEK
    suggested: None
    African green monkey (Vero-E6) cells were added in a concentration of 2 × 104 cells per well and incubated for 3 days at 35°C in an incubator with 5% carbon dioxide.
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    For the remaining 676 samples collected between March 30 and August 14, the longitudinal changes in IgG antibody levels were analyzed by linear mixed effects modeling in R (v3.6.0) using the LmerTest package (v3.1.2).
    LmerTest
    suggested: (R package: lmerTest, RRID:SCR_015656)
    Statistical analysis were carried out using Graphpad Prism 7.
    Graphpad Prism
    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 is the substantial uncertainty in the individual half-life estimates especially at the low end, since the available data will sometimes only cover a fraction of a half-life. Long-term maintenance of antibody production is provided by a pool of long-lived plasma cells and memory B-cells that can last a lifetime [35]. Several time scales may be identified, of which the longest-lasting can have half-lifes in the order of many years, and thus beyond scope of the current study [36]. It will be interesting to continue following the decline of anti-RBD IgG in time and investigate whether the longevity of the antibody response is similar to other coronaviruses, such as SARS-CoV that can still be detected in most individuals 3-years after recovery [37]. The antibody titer required for protection against re-infection in humans is not yet known, and has to be evaluated also in the context of a recall response upon re-infection. Recent studies provide evidence that upon infection, individuals develop SARS-CoV-2 specific memory B and memory T cells that can be detected for up to 240 days, with numbers of IgG memory B cells increasing over time and plateauing after ca. 150 days [20, 38]. The relationship between long-lasting antibody production and the T and B cell memory compartments requires more investigation. We also quantitatively examined the IgG1 and IgG3 subclass response and found that in our study population IgG1 appeared to be by far the dominant IgG subtype. This i...

    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.

    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.