Occurrence of COVID-19 Symptoms During SARS-CoV-2 Infection Defines Waning of Humoral Immunity

  1. Jun Wu
  2. Bo-Yun Liang
  3. Yao-Hui Fang
  4. Hua Wang
  5. Xiao-Li Yang
  6. Shu Shen
  7. Liang-Kai Chen
  8. Su-Meng Li
  9. Si-Hong Lu
  10. Tian-Dan Xiang
  11. Jia Liu
  12. Vu Thuy Khanh Le-Trilling
  13. Meng-Ji Lu
  14. Dong-Liang Yang
  15. Fei Deng
  16. Ulf Dittmer
  17. Mirko Trilling
  18. Xin Zheng

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Abstract

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals who mounted a detectable antibody response with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients did. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.

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  1. Version published to 10.3389/fimmu.2021.722027
  2. ScreenIT

    SciScore for 10.1101/2021.03.26.437123: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All patients signed a general written consent that residual blood samples can be applied for scientific research.
    IRB: All procedures were approved by the Ethics Commission of Union Hospital of Huazhong University of Science and Technology in Wuhan.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The levels of IgM and IgG antibodies recognizing the RBD of the S protein and the N protein (IgG-S, IgG-N, IgM-S, and IgM-N) were determined.
    IgG
    suggested: None
    IgG-S, IgG-N
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus neutralization test assay: The SARS-CoV-2-neutralizing activity of patient plasma was tested against SARS-CoV-2 (Strain BetaCoV/Wuhan/WIV04/2019, National Virus Resource Center number: IVCAS 6.7512) in highly permissive Vero E6 cells using the described co-incubation methodology(6).
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Longitudinal changes in antibody titers during April 2020 and October 2020 were depicted using the locally weighted regression and smoothing scatterplots (Lowess) model (ggplot2 package in R).
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    All statistical analyses were conducted using R (The R Foundation, http://www.r-project.org, version 4.0.0).
    http://www.r-project.org
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)

    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:
    Like all observational analyses, our study has certain limitations. Firstly, after half a year, a potential recall bias of asymptomatic carriers may affect the results of this study. Secondly, a fraction of asymptomatic patients may have been missed by our surveillance as consequence of IgG-S levels below the level of detection during the recovery period(10,16). This study only enrolled asymptomatic individuals, who mounted a detectable antibody response. In conclusion, half a year after the Wuhan COVID-19 epidemic ended, although asymptomatic individuals had lower IgG-S antibody titers, positivity rates, and neutralizing activities compared to symptomatic patients, nearly half of asymptomatic subjects had sufficient neutralization activity. These results suggest that a considerable fraction of asymptomatic natural infections stimulate a humoral immune response conferring the ability to resist reinfections. Despite this good news, above mentioned disparity in the strength and duration of IgG-S responses raised by symptomatic and asymptomatic infections, strongly argue in favour of vaccine programmes including individuals who underwent asymptomatic SARS-CoV-2 infections, ideally with an intermediate prioritization adjusted between vulnerable uninfected individuals and symptomatic COVID-19 patients.

    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.
    • No funding statement was detected.
    • 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.

  3. Version published to 10.1101/2021.03.26.437123v1 on bioRxiv