IgG Antibodies against SARS-CoV-2 Correlate with Days from Symptom Onset, Viral Load and IL-10

  1. Mary K. Young
  2. Christine Kornmeier
  3. Rebecca M. Carpenter
  4. Nick R. Natale
  5. Jennifer M. Sasson
  6. Michael D. Solga
  7. Amy J. Mathers
  8. Melinda D. Poulter
  9. Xiao Qiang
  10. William A. Petri

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Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a pandemic of the respiratory disease coronavirus disease 2019 (COVID-19). Antibody testing is essential to identify persons exposed to the virus and potentially in predicting disease immunity. 183 COVID-19 patients (68 of whom required mechanical ventilation) and 41 controls were tested for plasma IgG, IgA and IgM against the SARS-CoV-2 S1, S2, receptor binding domain (RBD) and N proteins using the MILLIPLEX ® SARS-CoV-2 Antigen Panel. Plasma cytokines were concurrently measured using the MILLIPLEX® MAP Human Cytokine/Chemokine/Growth Factor Panel A. As expected the 183 COVID-19 positive patients had high levels of IgG, IgA and IgM anti-SARS-CoV-2 antibodies against each of the viral proteins. Sensitivity of anti-S1 IgG increased from 60% to 93% one week after symptom onset. S1-IgG and S1-IgA had specificities of 98% compared to the 41 COVID-19 negative patients. The 68 ventilated COVID-19 positive patients had higher antibody levels than the 115 COVID-19 positive patients who were not ventilated. IgG antibody levels against S1 protein had the strongest positive correlation to days from symptom onset. There were no statistically significant differences in IgG, IgA and IgM antibodies against S1 based on age. We found that patients with the highest levels of anti-SARS-CoV-2 antibodies had the lowest viral load in the nasopharynx. Finally there was a correlation of high plasma IL-10 with low anti-SARS-CoV-2 antibodies. Anti-SARS-CoV-2 antibody levels, as measured by a novel antigen panel, increased within days after symptom onset, achieving > 90% sensitivity and specificity within one week, and were highest in patients who required mechanical ventilation. Antibody levels were inversely associated with viral load but did not differ as a function of age. The correlation of high IL-10 with low antibody response suggests a potentially suppressive role of this cytokine in the humoral immune response in COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2020.12.05.20244541: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The collection of blood samples and deidentified patient information was approved by the University of Virginia Institutional Review Board (IRB-HSR #22231 and 200110).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    IgG, IgA and IgM antibody levels against SARS-CoV-2 spike protein subunits S1 and S2, RBD and N were measured in duplicate plasma samples from the 224 patients using novel MILLIPLEX® SARS-CoV-2 Antigen Panel 1 IgG, SARS-CoV-2 Antigen Panel 1 IgA and SARS-CoV-2 Antigen Panel 1 IgM (Millipore Sigma, St. Louis, MO, Catalog Numbers: HC19SERG1-85K, HC19SERA1-85K, and HC19SERM1-85K respectively; For Research Use Only.
    IgM
    suggested: None
    SARS-CoV-2 spike protein subunits S1
    suggested: (Active Motif Cat# 91345, RRID:AB_2847847)
    novel MILLIPLEX® SARS-CoV-2 Antigen Panel 1 IgG, SARS-CoV-2 Antigen Panel 1 IgA
    suggested: None
    SARS-CoV-2 Antigen Panel 1 IgM (Millipore Sigma, St. Louis, MO, Catalog Numbers: HC19SERG1-85K, HC19SERA1-85K, and HC19SERM1-85K respectively; For Research Use
    suggested: None
    HC19SERA1-85K
    suggested: None
    50 µL of phycoerythrin-anti-human immunoglobulin (IgG, IgA or IgM per kit in use) detection antibody was added to each well, plate sealed and incubated 90 minutes at RT with constant shaking.
    phycoerythrin-anti-human immunoglobulin (IgG
    suggested: None
    Simple linear regression and Spearman correlations were used to associate antibody levels with days from symptom onset in COVID-19 and assess the relationship between viral load and IgG antibodies that are specific for SARS-CoV-2 antigens.
    IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Sensitivity and specificity were calculated in GraphPad Prism.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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.
    • Thank you for including a protocol registration statement.

    About SciScore

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  2. Version published to 10.1101/2020.12.05.20244541 on medRxiv