Severe Acute Respiratory Syndrome Coronavirus 2 Nucleocapsid Antigen in Urine of Hospitalized Patients With Coronavirus Disease 2019

  1. Nicolas Veyrenche
  2. Amandine Pisoni
  3. Ségolène Debiesse
  4. Karine Bollore
  5. Anne Sophie Bedin
  6. Alain Makinson
  7. Clémence Niel
  8. Carmen Alcocer-Cordellat
  9. Anne Marie Mondain
  10. Vincent Le Moing
  11. Philippe Van de Perre
  12. Edouard Tuaillon

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen (N-Ag) can be detected in the blood of patients with coronavirus disease 2019 (COVID-19). We used a highly sensitive and specific assay to explore the presence of N-Ag in urine during the course of COVID-19 and its relationship with the severity of disease.

Methods

We studied urinary and plasma N-Ag using a highly sensitive immunoassay in 82 patients with SARS-CoV-2 infection proved by polymerase chain reaction.

Results

In the first and second weeks of COVID-19, hospitalized patients tested positive for urinary N-Ag (81.25% and 71.79%, respectively) and plasma N-Ag (93.75% and 94.87%, respectively). High urinary N-Ag levels were associated with the absence of SARS-CoV-2 nucleocapsid antibodies, admission in intensive care units, high C-reactive protein levels, lymphopenia, eosinopenia, and high lactate dehydrogenase levels. Higher accuracy was observed for urinary N-Ag as a predictor of severe COVID-19 than for plasma N-Ag.

Conclusions

Our study demonstrates that N-Ag is present in the urine of patients hospitalized in the early phase of COVID-19. As a direct marker of SARS-CoV-2, urinary N-Ag reflects the dissemination of viral compounds in the body. Urinary N-Ag may be a useful marker for disease severity in SARS-CoV-2 infections.

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  1. Version published to 10.1093/infdis/jiac073
  2. ScreenIT

    SciScore for 10.1101/2021.09.28.21264239: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The cohort study received an institutional ethics committee approval (CPP Ile de France III, n°2020-A00935−34; ClinicalTrials. gov Identifier: NCT04347850).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    This assay detects IgG and IgA antibodies directed against the nucleocapsid of SARS-CoV-2 in plasma samples.
    IgA
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analyzed using Excel 2016 (Microsoft Corp, Redmond, Washington) and GraphPad Prism 9.1.1.0 (Microsoft Corp, Redmond, Washington).
    Excel
    suggested: None
    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: We detected the following sentences addressing limitations in the study:
    Our study has several limitations. The population is not representative of SARS-CoV-2 infected individuals. All of the subjects had mild or severe forms of Covid-19 and required oxygen, whereas a majority of SARS-CoV-2 infected individuals do not require hospitalization. In addition, patients requiring critical care are over-represented because their urine samples frequently were collected in routine care. We did not assess the value of N-Ag as a predictive marker of adverse evolution but only as a marker associated to severe Covid-19. Finally, N-Ag levels were analysed on a single urine sample while results on urine samples collected taken over a 24-hour period would be more accurate. In conclusion, these results demonstrate that N-Ag is present in urine of patients hospitalized for Covid-19. As a direct marker of SARS-CoV-2 infection, urinary and blood N-Ag reflect the dissemination of viral compounds in the body and probably SARS-CoV-2 replication. Further studies are required to evaluate the value of urinary N-Ag to predict the adverse evolution of SARS-CoV-2 infections.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04347850RecruitingA Cohort of Patients With Possible or Confirmed SARS-CoV-2 (…

    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.

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

    About SciScore

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  3. Version published to 10.1101/2021.09.28.21264239v2 on medRxiv
  4. Version published to 10.1101/2021.09.28.21264239v1 on medRxiv