Persistence of Robust Humoral Immune Response in Coronavirus Disease 2019 Convalescent Individuals Over 12 Months After Infection

  1. Kei Miyakawa
  2. Sousuke Kubo
  3. Sundararaj Stanleyraj Jeremiah
  4. Hirofumi Go
  5. Yutaro Yamaoka
  6. Norihisa Ohtake
  7. Hideaki Kato
  8. Satoshi Ikeda
  9. Takahiro Mihara
  10. Ikuro Matsuba
  11. Naoko Sanno
  12. Masaaki Miyakawa
  13. Masaharu Shinkai
  14. Tomoyuki Miyazaki
  15. Takashi Ogura
  16. Shuichi Ito
  17. Takeshi Kaneko
  18. Kouji Yamamoto
  19. Atsushi Goto
  20. Akihide Ryo

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). In this study, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months.

Methods

The study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of immunoglobulin (Ig)G to the viral nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein were measured by chemiluminescence enzyme immunoassay. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus.

Results

Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. Although the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs).

Conclusions

Coronavirus disease 2019 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.

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  1. Version published to 10.1093/ofid/ofab626
  2. ScreenIT

    SciScore for 10.1101/2021.09.27.21264013: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All participants provided written informed consent and the study was approved by the Institutional Review Board of Yokohama City University (
    IRB: All participants provided written informed consent and the study was approved by the Institutional Review Board of Yokohama City University (
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The primary endpoints of this study were NT50 and titers of antibodies against NP and SP antigens at 20–32 weeks (visit 1) and 46– 58 weeks (visit 2) after the first positive SARS-CoV-2 test results.
    antibodies against NP
    suggested: (Novus Cat# NBP1-00943, RRID:AB_1503763)
    Experimental Models: Cell Lines
    SentencesResources
    For the neutralizing assay, VeroTM cells seeded in 96-well plates were washed and infected with 100 µL of medium containing authentic SARS-CoV-2 (moi = 0.05) and five-fold serially diluted serum (1:50–1:31,250 dilution).
    VeroTM
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical Analysis: All statistical analysis was performed using Prism v8.3.1 (GraphPad) and R version 4.0.3 (R, Foundation for Statistical Computing).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    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: 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.
    • Thank you for including a protocol registration statement.

    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.

  3. Version published to 10.1101/2021.09.27.21264013v1 on medRxiv