Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan – implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2

  1. Tao Liu
  2. Sanyun Wu
  3. Huangheng Tao
  4. Guang Zeng
  5. Fuling Zhou
  6. Fangjian Guo
  7. Xinghuan Wang

Reviewed by

Read the full article

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

Background

It is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China.

Methods

We included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded.

Results

IgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients.

Conclusions

Very few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.

Primary Funding Sources

Part of the study was supported by National Key Research and Development Program of China (2020YFC0845500). The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors.

Role of the Funder/Sponsor

The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication.

Data and code availability statement

Data and analyses codes are available from the corresponding authors on request. All request for raw and analyzed data and materials will be reviewed by the corresponding authors to verify whether the request is subject to any intellectual property or confidentiality obligations. Access will be granted after a signed data access agreement is attained.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.06.13.20130252: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study Design and Participants: The study was approved by the institutional ethics board at Zhongnan Hospital of Wuhan University.
    Consent: Requirement for written informed consent was waived by the institutional ethics board for emerging infectious diseases.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Methods for testing serum IgM and IgG antibodies to SARS-CoV-2 were previously described.
    IgG
    suggested: None
    , anti-human IgM monoclonal antibody, and anti-human IgG monoclonal antibody.
    anti-human IgM
    suggested: None
    anti-human IgG
    suggested: None
    Kaplan-Meier curves were plotted to show survival differences in hospitalized COVID-19 patients by the status of IgG antibodies to SARS-CoV-2.
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses were conducted using SAS software version 9.4
    SAS
    suggested: (SASqPCR, RRID:SCR_003056)

    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:
    Limitations of this study include that we do not have long-term follow-up data on recovered COVID-19 patients. Whether or not those patients will lose COVID-19 IgG antibodies in the next few months is still to be studied. Additionally, COVID-19 IgM/IgG test does not have perfect sensitivity and specificity for detecting IgG antibodies to SARS-CoV-2 in the serum. Nevertheless, we observed that very few healthcare providers without a confirmed COVID-19 diagnosis had a positive test result. This observed phenomenon strongly suggests that long-term protective antibodies are unlikely produced after SARS-CoV-2 infection. In conclusion, very few healthcare providers without confirmed COVID-19 diagnosis in Wuhan have IgG antibodies to SARS-CoV-2, though a substantial portion of them had been infected with the virus. More than 10% of COVID-19 patients did not have those antibodies after 21 days post symptom onset. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.

    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. ScreenIT

    SciScore for 10.1101/2020.06.13.20130252: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementOnline Methods Study Design and Participants The study was approved by the institutional ethics board at Zhongnan Hospital of Wuhan University .Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Prevalence of IgM antibodies to SARS-CoV-2 was 31.4 % in COVID-19 patients , 1.5 % in healthcare providers , 1.3 % in general workers , and 0.2 % in other patients .
    IgM
    suggested: None
    Conclusions Very few healthcare providers had IgG antibodies to SARS-CoV-2 , though a significant proportion of them had been infected with the virus .
    had IgG
    suggested: None
    The last RT-PCR tests for SARS-CoV-2 were positive in only eight COVID-19 patients and none of three patients was tested negative for IgG antibodies to SARS-CoV-2 . Prevalence of IgG and IgM antibodies to SARS-CoV-2 Prevalence of IgG antibodies to SARS-CoV-2 was 89.8 % ( 95 % CI 88.2-91.3 % ) in COVID-19 patients ( Table 2 ) compared to 4.0 % ( 95 % CI 3.4-4.7 % ) in healthcare providers , 4.6 % ( 95 % CI 4.3-4.9 % ) in general workers , and 1.0 % in other patients ( p all <0.001 for comparing to COVID-19 patients) .
    SARS-CoV-2 . Prevalence of IgG
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>SARS-CoV-2 Prevalence of IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Mortality rate was 1.3 ( 95 % CI 0.7-1.9 % ) in those with IgG antibodies to SARS-CoV-2 and was 3.3 % ( 95 % CI 0.4-6.2 % ) in those without ( Figure 1) .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">After infection with SARS-CoV-1 , patients start to produce SARS-specific IgG antibody in the second week , which persists for a long time31,32 .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>SARS-specific IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Even after 210 days after symptom onset , neutralizing viral antibodies ( anti-viral IgG ) are still detectable in recovered SARS patients33 .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>anti-viral IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">A recent study characterized the viral spike protein receptor-binding domainspecific monoclonal antibodies derived from single B cells of patients with COVID-19.43 In that study , the three most server cases ( one dead ) had much higher plasma binding activities to SARS-CoV-2 spike protein , spike protein receptor-binding domain , and nucleocapsid protein than the other five cases with mild symptoms , which casts some doubts on the relationship between antibody response and disease progression and the utilization of neutralizing antibodies as prophylactic and therapeutic SARS-CoV-2 interventions .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>nucleocapsid protein than the other five cases with mild symptoms , which casts some doubts on the relationship between antibody response and disease progression and the utilization of neutralizing antibodies as prophylactic and therapeutic SARS-CoV-2 interventions</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Second , COVID-19 IgG antibodies as tested by the kits may simply serve as a sign of the infection status and might not be protective neutralizing antibodies .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>COVID-19 IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">However , none of them developed long-lasting protective antibodies against SARS-CoV-2 .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>SARS-CoV-2</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Additionally , COVID-19 IgM/IgG test does not have perfect sensitivity and specificity for detecting IgG antibodies to SARS-CoV-2 in the serum .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>detecting IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">anti-human IgM monoclonal antibody , and anti-human IgG monoclonal antibody .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>anti-human IgM</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>anti-human IgG</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Statistical analyses were conducted using SAS software version 9.4</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>SAS</b></div>
        <div>suggested: (SASqPCR, <a href="https://scicrunch.org/resources/Any/search?q=SCR_003056">SCR_003056</a>)</div>
      </div>
    </td></tr></table>

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

    • Limitations of this study include that we do not have long-term follow-up data on recovered COVID-19 patients.
    • Whether or not those patients will lose COVID-19 IgG antibodies in the next few months is still to be studied.

    Results from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.06.13.20130252 on medRxiv