Fine Analysis of Lymphocyte Subpopulations in SARS-CoV-2 Infected Patients: Differential Profiling of Patients With Severe Outcome

  1. Giovanna Clavarino
  2. Corentin Leroy
  3. Olivier Epaulard
  4. Tatiana Raskovalova
  5. Antoine Vilotitch
  6. Martine Pernollet
  7. Chantal Dumestre-Pérard
  8. Federica Defendi
  9. Marion Le Maréchal
  10. Audrey Le Gouellec
  11. Pierre Audoin
  12. Jean-Luc Bosson
  13. Pascal Poignard
  14. Matthieu Roustit
  15. Marie-Christine Jacob
  16. Jean-Yves Cesbron

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Abstract

COVID-19 is caused by the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in widespread morbidity and mortality. CD4 + T cells, CD8 + T cells and neutralizing antibodies all contribute to control SARS-CoV-2 infection. However, heterogeneity is a major factor in disease severity and in immune innate and adaptive responses to SARS-CoV-2. We performed a deep analysis by flow cytometry of lymphocyte populations of 125 hospitalized SARS-CoV-2 infected patients on the day of hospital admission. Five clusters of patients were identified using hierarchical classification on the basis of their immunophenotypic profile, with different mortality outcomes. Some characteristics were observed in all the clusters of patients, such as lymphopenia and an elevated level of effector CD8 + CCR7 - T cells. However, low levels of T cell activation are associated to a better disease outcome; on the other hand, profound CD8 + T-cell lymphopenia, a high level of CD4 + and CD8 + T-cell activation and a high level of CD8 + T-cell senescence are associated with a higher mortality outcome. Furthermore, a cluster of patient was characterized by high B-cell responses with an extremely high level of plasmablasts. Our study points out the prognostic value of lymphocyte parameters such as T-cell activation and senescence and strengthen the interest in treating the patients early in course of the disease with targeted immunomodulatory therapies based on the type of adaptive response of each patient.

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  1. Version published to 10.3389/fimmu.2022.889813
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    SciScore for 10.1101/2021.08.31.21262538: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Patients were informed and non-opposition (BioMarCoViD retrospective study) or written consent (AcNT-COVID-19 prospective study) was obtained, according to French law.
    IRB: Ethical approval for the prospective study was given by the relevant ethics committee (Comité de Protection des Personnes Ile de France II, N°IDRCB: 2020-A00904-35) and registered in clinicaltrial.gov (NCT04596098).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Acquisition was performed using BD FACSCanto-II flow cytometer (BD Biosciences, San José, CA) and analysis done with BD FACSDiva 8 software (BD Biosciences, San José, CA).
    BD FACSDiva
    suggested: (BD FACSDiva Software, RRID:SCR_001456)

    Results from OddPub: Thank you for sharing your data.

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04596098RecruitingImmune Responses to COVID-19; Isolation of Neutralizing Anti…

    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.

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  3. Version published to 10.1101/2021.08.31.21262538v1 on medRxiv