Stable neutralizing antibody levels six months after mild and severe COVID-19 episode

  1. Edwards Pradenas
  2. Benjamin Trinité
  3. Víctor Urrea
  4. Silvia Marfil
  5. Carlos Ávila-Nieto
  6. María Luisa Rodríguez de la Concepción
  7. Ferran Tarrés-Freixas
  8. Silvia Pérez-Yanes
  9. Carla Rovirosa
  10. Erola Ainsua-Enrich
  11. Jordi Rodon
  12. Júlia Vergara-Alert
  13. Joaquim Segalés
  14. Victor Guallar
  15. Alfonso Valencia
  16. Nuria Izquierdo-Useros
  17. Roger Paredes
  18. Lourdes Mateu
  19. Anna Chamorro
  20. Marta Massanella
  21. Jorge Carrillo
  22. Bonaventura Clotet
  23. Julià Blanco

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Abstract

Understanding mid-term kinetics of immunity to SARS-CoV-2 is the cornerstone for public health control of the pandemic and vaccine development. However, current evidence is rather based on limited measurements, thus losing sight of the temporal pattern of these changes 1–6 . In this longitudinal analysis, conducted on a prospective cohort of COVID-19 patients followed up to 242 days, we found that individuals with mild or asymptomatic infection experienced an insignificant decay in neutralizing activity that persisted six months after symptom onset or diagnosis. Hospitalized individuals showed higher neutralizing titers, which decreased following a two-phase pattern, with an initial rapid decline that significantly slowed after day 80. Despite this initial decay, neutralizing activity at six months remained higher among hospitalized individuals. The slow decline in neutralizing activity at mid-term contrasted with the steep slope of antibody titers change, reinforcing the hypothesis that the quality of immune response evolves over the post-convalescent stage 4,5 .

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  1. ScreenIT

    SciScore for 10.1101/2020.11.22.389056: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study overview and subjects: The study was approved by the Hospital Ethics Committee Board from Hospital Universitari Germans Trias i Pujol, HUGTiP (reference PI-20-122 and PI-20-217) and all participants provided written informed consent before inclusion.
    Consent: Study overview and subjects: The study was approved by the Hospital Ethics Committee Board from Hospital Universitari Germans Trias i Pujol, HUGTiP (reference PI-20-122 and PI-20-217) and all participants provided written informed consent before inclusion.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Briefly, Nunc MaxiSorp ELISA plates were coated with 50 μL of capture antibody (anti-6x-His antibody clone HIS.H8; 2 μg/mL; Thermo Fisher Scientific, Waltham, MA, USA) in phosphate-buffered saline (PBS) overnight at 4°C.
    anti-6x-His
    suggested: None
    The HRP conjugated (Fab)2 goat anti-human IgG (Fc specific) (1/20,000) (Jackson ImmunoResearch, Ely, UK) was used as a secondary antibody and incubated for 30 minutes at room temperature.
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Supernatants were harvested 48 hours after transfection, filtered at 0.45 μm, frozen, and titrated on HEK293T cells overexpressing WT human ACE-2 (Integral Molecular, Philadelphia, PA, USA).
    HEK293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    Then, 2×104 HEK293T/hACE2 cells (Integral Molecular) treated with DEAE-Dextran (Sigma-Aldrich) were added.
    HEK293T/hACE2
    suggested: None
    Software and Algorithms
    SentencesResources
    The KING cohort included more than 200 individuals with a documented positive RT-qPCR result from nasopharyngeal swab and/or a positive serological ELISA test performed in our hospital, irrespective of age and disease severity―including asymptomatic status.
    KING
    suggested: (KING, RRID:SCR_009251)
    The values were normalized, and the ID50 was calculated by plotting the log of plasma dilution vs. response―Variable slope (four parameters) in Prism 8.4.3 (GraphPad Software, San Diego, CA, USA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    All analyses were performed with Prism 8.4.3 (GraphPad Software) and R version 4.0 (R Foundation for Statistical Computing).
    Prism
    suggested: (PRISM, RRID:SCR_005375)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

  2. Version published to 10.1101/2020.11.22.389056 on bioRxiv