Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in early COVID-19 infection

  1. Xiaomei Zhang
  2. Xian Wu
  3. Dan Wang
  4. Minya Lu
  5. Xin Hou
  6. Hongye Wang
  7. Te Liang
  8. Jiayu Dai
  9. Hu Duan
  10. Yingchun Xu
  11. Yongzhe Li
  12. Xiaobo Yu

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Abstract

Rapid and accurate tests that detect IgM and IgG antibodies to SARS-CoV-2 proteins are essential in slowing the spread of COVID-19 by identifying patients who are infected with COVID-19. Using a SARS-CoV-2 proteome microarray developed in our lab, we comprehensively profiled both IgM and IgG antibodies in forty patients with early-stage COVID-19, influenza, or non-influenza who had similar symptoms. The results revealed that the SARS-CoV-2 N protein is not an ideal biomarker for COVID-19 diagnosis because of its low immunogenicity, thus tests that rely on this marker alone will have a high false negative rate. Our data further suggest that the S protein subunit 1 receptor binding domain (S1-RBD) might be the optimal antigen for IgM antibody detection, while the S protein extracellular domain (S1+S2ECD) would be the optimal antigen for both IgM and IgG antibody detection. Notably, the combination of all IgM and IgG biomarkers can identify 87% and 73.3% COVID-19 patients, respectively. Finally, the COVID-19-specific antibodies are significantly correlated with the clinical indices of viral infection and acute myocardial injury (p≤0.05). Our data may help understand the function of anti-SARS-CoV-2 antibodies and improve serology tests for rapid COVID-19 screening.

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    SciScore for 10.1101/2020.04.14.20064535: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: All serum samples were collected under the approval of the intuitional review board (IRB) from Peking Union Medical College Hospital (Ethical number: ZS-2303) and Beijing Proteome Research Center.
    Consent: Written informed consent was waived due to the rapid emergence of this infectious disease.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The array was then incubated for 30 min with a mixture containing Cy3 Affinipure donkey anti-human IgG(H+L) and Alexa Fluor 647 Affinipure goat anti-human IgM FC5µ antibody (Jackson ImmunoResearch, USA) (2μg/mL).
    anti-human IgG(H+L
    suggested: None
    anti-human IgM FC5µ
    suggested: None
    Differentially-expressed SARS-CoV-2 antibodies were identified using Mann Whitney U-test with a p-value of 0.05.
    Differentially-expressed SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    The circos plot was made using circos (http://circos.ca/).
    circos
    suggested: (Circos, RRID:SCR_011798)

    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 10.1101/2020.04.14.20064535 on medRxiv