Serum SARS-CoV-2 Antigens for the Determination of COVID-19 Severity

  1. Julien Favresse
  2. Jean-Louis Bayart
  3. Clara David
  4. Constant Gillot
  5. Grégoire Wieërs
  6. Gatien Roussel
  7. Guillaume Sondag
  8. Marc Elsen
  9. Christine Eucher
  10. Jean-Michel Dogné
  11. Jonathan Douxfils

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Abstract

The diagnostic of SARS-CoV-2 infection relies on reverse transcriptase polymerase chain reactions (RT-PCRs) performed on nasopharyngeal (NP) swabs. Nevertheless, false-negative results can be obtained with inadequate sampling procedures, making the use of other biological matrices worthy of investigation. This study aims to evaluate the kinetics of serum N antigens in severe and non-severe patients and compare the clinical performance of serum antigenic assays with NP RT-PCR. Ninety patients were included in the study and monitored for several days. Disease severity was determined according to the WHO clinical progression scale. Serum N antigen levels were measured with a chemiluminescent assay (CLIA) and the Single Molecular Array (Simoa) assay. Viremia thresholds for severity were determined and proposed. In severe patients, the peak antigen response was observed 7 days after the onset of symptoms, followed by a decline. No real peak response was observed in non-severe patients. Severity thresholds for the Simoa and the CLIA provided positive likelihood ratios of 30.0 and 10.9 for the timeframe between day 2 and day 14, respectively. Sensitive detection of N antigens in serum may thus provide a valuable new marker for COVID-19 diagnosis and evaluation of disease severity. When assessed during the first 2 weeks since the onset of symptoms, it may help in identifying patients at risk of developing severe COVID-19 to optimize better intensive care utilization.

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  1. Version published to 10.3390/v14081653
  2. ScreenIT

    SciScore for 10.1101/2021.11.18.21266478: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol is available upon request and was in accordance with the Declaration of Helsinki and approved by the Medical Ethical Committee of Saint-Luc Bouge (Bouge, Belgium, approval number B0392020000005).
    Sex as a biological variableAmong the 90 included patients, 44 (48.9%) were females (median age = 78 years, min-max = 20-97) and 46 (51.1%) were male (median age = 77 years, min-max =
    Randomizationnot detected.
    Blinding(18) Reviewers of the medical records and technicians who performed the analyses were blinded and not allow to communicate on the results.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Briefly, diluted sample and anti-N protein antibody coated capture beads and detector antibodies are combined for 35 minutes in the cuvette in a first step.
    anti-N protein
    suggested: None
    Antigens in the sample will react with anti-2019-nCoV antibodies coated on paramagnetic particles and with anti-2019-nCoV acridinium-ester-labeled conjugate to form a sandwich complex.
    anti-2019-nCoV
    suggested: None
    SARS-CoV-2 Spike IgG: SARS-CoV-2 Spike IgG antibodies were quantified automatically in patient sera by a Simoa immunoassay using the Simoa HD-X analyzer (Quanterix, Massachusetts, USA).
    Spike IgG: SARS-CoV-2 Spike IgG
    suggested: None
    (20) SARS-CoV-2 antibodies were available for 77 patients out of the 81 (95.1%) due to insufficient residual serum sample.
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Data analysis was performed using GraphPad Prism software (version 9.2.0, California, USA) and MedCalc software (version 14.8.1, Ostend, Belgium).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    MedCalc
    suggested: (MedCalc, RRID:SCR_015044)

    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.

    Results from scite Reference Check: We found no unreliable references.

    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.

  3. Version published to 10.1101/2021.11.18.21266478v1 on medRxiv