The production and clinical implications of SARS-CoV-2 antibodies

  1. Qianfang Hu
  2. Xiaoping Cui
  3. Xinzhu Liu
  4. Bin Peng
  5. Jinyue Jiang
  6. Xiaohui Wang
  7. Yan Li
  8. Wenhui Hu
  9. Zhi Ao
  10. Jun Duan
  11. Xue Wang
  12. Linxiao Zhu
  13. Guicheng Wu
  14. Shuliang Guo

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), a novel betacoronavirus, has caused an outburst of pneumonia cases in Wuhan, China. We report the production of specific IgM and IgG antibodies after the infection of SARS-CoV-2 and its implication for the diagnosis, pathology and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge.

Methods

Test results for SARS-CoV-2 IgM and IgG antibodies of 221 confirmed COVID-19 patients were retrospectively examined, and their clinical data were collected and analyzed based on various subgroups. SARS-CoV-2 IgM and IgG antibodies were determined with the chemiluminescence method.

Findings

The concentration (S/CO) of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, with a median of 17.38 (IQR 4.39-36.4) for IgM and 5.59 (IQR 0.73-13.65) for IgG. Detection rates reached highest on day 16-18 and day 19-21 for IgM and IgG, which were 73.6% and 98.6%, respectively, with significantly higher concentration of IgG in critically ill patients than in those with mild to moderate disease (P=0.027). The concentration of the antibodies on day 16-21 is not correlated with the course or outcome of the disease (Spearman r < 0.20, P > 0.05). Nasopharyngeal swabs revealed positive SARS-CoV-2 RNA in up to 52.7% of recovered patients after discharge, whose IgG proved to be significantly lower than that of those with negative RNA results (P = 0.009). IgG and IgM were tested twice within 14 days after discharge with a 7-day interval, and the second testing of these antibodies displayed a decrease in concentration of 21.2% (IQR, 11.2%,34.48%) for IgG and 23.05% (IQR, −27.96%,46.13%) for IgM, without statistical significance between the patients with re-detectable positive RNA results and those with negative RNA results after discharge. However, those with positive results experienced a count decrease in lymphocyte subsets.

Interpretation

The concentration of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, and antibody testing on day 16-21 is associated with increased detection rates, but the antibody concentration does not affect the course and outcome of the infection. Recovering patients with re-detectable positive SARS-CoV-2 RNA displayed lower concentration of IgG, but the downward trend of IgG during recovery indicated its limited duration of protection, and the protective effect of IgG remains to be investigated.

Funding

Chongqing Education Board, Chongqing Science and Technology Bureau, Famous teacher project of Chongqing talent plan

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  1. ScreenIT

    SciScore for 10.1101/2020.04.20.20065953: (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 Chongqing Medical University (approval number 20200601).
    Consent: Due to the special reasons of the epidemic, the patients’ informed consent was not obtained.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThere were 86 female and 135 male patients, with an average age of 47·8 (47·8±15·1) years.

    Table 2: Resources

    Antibodies
    SentencesResources
    The 145 patients with initial antibody testing results upon admission were divided according to positive and negative IgM and positive and negative IgG, and the following information and their association with antibody production were examined: age, the length between antibody detection and symptom onset, severity of the disease, comorbidity, fever at symptom onset, count of white blood cells, neutrophils, lymphocytes, T and B lymphocytes, CD4 and CD8 lymphocytes, natural killer cells and CD4/CD8 ratio, procaicitonin, interleukin-6, tumor necrosis factor-α, γ-interferon within 3 days after admission and pulmonary inflammation index (PII) value calculated according to Jiong Wu et al.6 The relation of antibody concentration with the duration of positive virus detection (the duration between first and last positive nucleic acid testing), duration of fever (the duration between first and last detection of fever as defined by temperature > 37·3°C), length hospital stay, the progression of PII (PII value on day 7-10 after admission minus that within 3 days after admission) and outcome of the disease was investigated with the antibody testing result of 78 patients on day 16-21 after symptom onset.
    CD4
    suggested: None
    CD8
    suggested: None
    interleukin-6
    suggested: None
    The predictive value of SARS-CoV-2 IgG and IgM antibody concentration for re-detectable positive nucleic acid testing was investigated with antibody testing results of 74 recovered patients within 7 days after discharge.
    IgM
    suggested: None
    The recombinant antigens containing the nucleoprotein and a peptide from the SARS-CoV-2 spike protein were conjugated with fluorescein isothiocyanate (FITC) and immobilized on the anti-FITC antibody-conjugated magnetic particles.
    anti-FITC
    suggested: None
    Alkaline phosphatase-conjugated human IgG/IgM antibody was used as the detection antibody.
    human IgG/IgM
    suggested: None

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2020.04.20.20065953v1 on medRxiv