Neutralizing and binding antibody kinetics of COVID-19 patients during hospital and convalescent phases

  1. Xiang-Yang Yao
  2. Wei Liu
  3. Zhi-Yong Li
  4. Hua-Long Xiong
  5. Ying-Ying Su
  6. Ting-Dong Li
  7. Shi-Yin Zhang
  8. Xue-Jie Zhang
  9. Zhao-Feng Bi
  10. Chen-Xi Deng
  11. Cai-Yu Li
  12. Quan Yuan
  13. Jun Zhang
  14. Tian-Ying Zhang
  15. Zhan-Xiang Wang
  16. Sheng-Xiang Ge
  17. Ning-Shao Xia

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Abstract

Knowledge of the host immune response after natural SARS-CoV-2 infection is essential for informing directions of vaccination and epidemiological control strategies against COVID-19. In this study, thirty-four COVID-19 patients were enrolled with 244 serial blood specimens (38.1% after hospital discharge) collected to explore the chronological evolution of neutralizing (NAb), total (TAb), IgM, IgG and IgA antibody in parallel. IgG titers reached a peak later (approximately 35 days postonset) than those of Nab, Ab, IgM and IgA (20∼25 days postonset). After peaking, IgM levels declined with an estimated average half-life of 10.36 days, which was more rapid than those of IgA (51.25 days) and IgG (177.39 days). Based on these half-life data, we estimate that the median times for IgM, IgA and IgG to become seronegative are 4.59 (IQR 4.12-5.03), 7.78 (IQR 6.71-9.16) and 42.72 (IQR 33.75-47.96) months post disease onset. The relative contribution of IgM to NAb was higher than that of IgG (standardized β regression coefficient: 0.53 vs 0.48), so the rapid decline in NAb may be attributed to the rapid decay of IgM in acute phase. However, the relative contribution of IgG to NAb increased and that of IgM further decreased after 6 weeks postonset. It’s assumed that the decline rate of NAb might slow down to the same level as that of IgG over time. This study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in patients and that humoral immunity against SARS-CoV-2 acquired by infection may persist for a relatively long time.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.18.20156810: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Medical Ethical Committee of the First Affiliated Hospital of Xiamen University.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Binding antibody testing: TAb, IgG, IgM and IgA against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in the sera of COVID-19 patients were tested using commercially available enzyme-linked immunosorbent assay (ELISA) kits, which were manufactured by Beijing Wantai Biological Pharmacy Enterprise Co., Ltd. (Beijing, China).
    IgA against the receptor-binding domain ( RBD
    suggested: None
    Software and Algorithms
    SentencesResources
    All statistical analyses were conducted using SAS 9.4 (SAS Institute, Cary, NC, USA), and graphs were drawn with GraphPad Prism 8.0 (GraphPad Software Inc.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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:
    There are some limitations that should be noted in this study. First, the sample size of 34 patients was small. However, only 35 patients were admitted to our hospital during the study period, and 97.1% of them were enrolled. Second, majority of subjects exhibited mild illness, and only 4 severe/critical cases and no asymptomatic individuals were included. The antibody kinetics of severe/critical and asymptomatic patients likely differ from those observed in this study. Third, due to the convenient collection of blood samples, the sample numbers of each patient varied widely among all patients, and the majority of samples were collected from week 2 to week 4 after illness onset (Supplementary Figure 3). Finally, the follow-up time was short (from 17 to 98 days after onset), and the duration of specific antibodies was estimated only based on the mean rate of decline during the early convalescent phase. The real lasting duration of immunity against SARS-CoV-2 in COVID-19 patients needs to be further investigated in the future with cohort follow-up for several years. In conclusion, this study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in all patients. The mean peak time for IgG was longer than that of IgM and IgA, and the titer of serum IgA was significantly lower than that of IgM and IgG. IgM may play an important role in neutralization during the early convalescent phase, but the contributions of IgG to NAb will increase with ...

    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 10.1101/2020.07.18.20156810v1 on medRxiv