Elevated serum IgM levels indicate poor outcome in patients with coronavirus disease 2019 pneumonia: A retrospective case-control study

  1. Zhihua Wang
  2. Huijun Li
  3. Jingjing Li
  4. Chunguang Yang
  5. Xiaolin Guo
  6. Zhiquan Hu
  7. Zhiqiang Chen
  8. Shaogang Wang
  9. Jihong Liu

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Abstract

Background

The coronavirus disease 2019 (COVID-19) pneumonia outbreak began in Wuhan and pandemics tend to occur. Although SARS-CoV-2-specific immunoglobulins have been detected in serum of COVID-19 patients, their dynamics and association with outcomes have not been characterized.

Methods

A total of 116 hospitalized patients with confirmed COVID-19 pneumonia and SARS-CoV-2-specific immunoglobulins tested in Tongji hospital were retrospectively investigated. Clinical, laboratory, radiological characteristics and outcomes data were compared between mild-moderate group and died group. Further, a paired case-control study was conducted where each deceased case was matched to three mild-moderate patients of similar age.

Findings

Among 116 subjects included, 101 mild-moderate patients survived and 15 cases died. SARS-CoV-2-specific IgM levels peaked in forth week after onset of COVID-19 pneumonia, while serum IgG levels increased over 8 weeks. Serum IgM levels were higher in deceased patients than mild-moderate patients (P = 0.024), but not IgG. Serum IgM levels were negatively correlated with clinical outcome, eosinophil count and albumin levels (r = −0.269, P = 0.003; r = −0.188, P = 0.043; and r = −0.198, P = 0.033, resp.). The area under the ROC curve (AUC) for IgM antibody was 0.681 (95% CI: 0.517-0.845, P = 0.024). In case-control study paired by age, serum IgM was higher in deceased patients than mild-moderate patients (P = 0.019), positively correlated with leucocyte count (r = 0.260, P = 0.045), while negatively correlated with clinical outcome and albumin levels (r = −0.337, P = 0.008; r = −0.265, P = 0.041). AUC for IgM levels was 0.704 (95% CI: 0.534-0.873, P = 0.019).

Interpretation

These results indicate that dynamics of SARS-CoV-2 specific IgM and IgG antibodies was similar with that of SARS-CoV, while elevated serum IgM levels indicate poor outcome in patients with COVID-19 pneumonia.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.22.20041285: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was reviewed and approved by the Medical Ethical Committee of Tongji Hospital of Huazhong University of Science and Technology (IRB ID:TJ-IRB20200343).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    In brief, the patients in mild-moderate group described here were all probable hospitalized subjects in four wards of Tongji hospital with (1) serum IgM and IgG against SARS-CoV-2 examined, (2) chest radiographic evidence of pneumonia, (3) positive throat swab nucleic acid test by real-time RT-PCR methods or ≥ a fourfold increase in specific antibodies by the chemiluminescence kit.
    IgG against SARS-CoV-2 examined, (2
    suggested: None
    Antibody measurement: Serum IgM and IgG antibodies were detected by the chemiluminescence kit (iFlash-SARS-CoV-2 IgM, iFlash-SARS-CoV-2 IgG) and iFlash 3000 CLIA System supplied by Yhlo Biotech Co. LTD (Shenzhen, China), of which the chemiluminescence kit had completed the EU CE certification.
    IgG
    suggested: None
    iFlash-SARS-CoV-2 IgM, iFlash-SARS-CoV-2 IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: The statistical software SPSS 23.0 was used in this study.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    This study also has limitations. It is a single-centre retrospective study with limited cases. Majority of patients admitted in our hospital were critically ill, so population bias exists. In addition, results of viral load and antibody re-testing were not available. In summary, our results demonstrate that dynamics of IgM and IgG antibodies against SARS-CoV-2 was similar with that of SARS-CoV. Differently, elevated serum IgM levels indicate poor outcome in patients with COVID-19 pneumonia.

    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 10.1101/2020.03.22.20041285v1 on medRxiv