T Cell Activation, Highly Armed Cytotoxic Cells and a Shift in Monocytes CD300 Receptors Expression Is Characteristic of Patients With Severe COVID-19

  1. Olatz Zenarruzabeitia
  2. Gabirel Astarloa-Pando
  3. Iñigo Terrén
  4. Ane Orrantia
  5. Raquel Pérez-Garay
  6. Iratxe Seijas-Betolaza
  7. Javier Nieto-Arana
  8. Natale Imaz-Ayo
  9. Silvia Pérez-Fernández
  10. Eunate Arana-Arri
  11. Francisco Borrego

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Abstract

COVID-19 manifests with a wide diversity of clinical phenotypes characterized by dysfunctional and exaggerated host immune responses. Many results have been described on the status of the immune system of patients infected with SARS-CoV-2, but there are still aspects that have not been fully characterized or understood. In this study, we have analyzed a cohort of patients with mild, moderate and severe disease. We performed flow cytometric studies and correlated the data with the clinical characteristics and clinical laboratory values of the patients. Both conventional and unsupervised data analyses concluded that patients with severe disease are characterized, among others, by a higher state of activation in all T cell subsets (CD4, CD8, double negative and T follicular helper cells), higher expression of perforin and granzyme B in cytotoxic cells, expansion of adaptive NK cells and the accumulation of activated and immature dysfunctional monocytes which are identified by a low expression of HLA-DR and an intriguing shift in the expression pattern of CD300 receptors. More importantly, correlation analysis showed a strong association between the alterations in the immune cells and the clinical signs of severity. These results indicate that patients with severe COVID-19 have a broad perturbation of their immune system, and they will help to understand the immunopathogenesis of COVID-19.

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  1. Version published to 10.3389/fimmu.2021.655934
  2. ScreenIT

    SciScore for 10.1101/2020.12.22.423917: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All donors provided written and signed informed consent in accordance with the Declaration of Helsinki.
    IRB: This study was approved by the Basque Ethics Committee for Research with Medicines (CEIm-E) with the number CES-BIOEF 2020-13.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Flow cytometry data analysis: FCS 3.0 files were exported from the FACSDiva and imported into FlowJo v.10.7.1. for subsequent analysis.
    FACSDiva
    suggested: (BD FACSDiva Software, RRID:SCR_001456)
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    The following plug-ins were used: DownSample (1.1), tSNE and FlowSOM (2.6).
    FlowSOM
    suggested: (FlowSOM, RRID:SCR_016899)
    Statistical analysis and data representation: GraphPad Prism v.
    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:
    A possible limitation of our study is the size of the cohort of patients with COVID-19 (n=44) and HC (n=12). However, and to avoid problems related to the diversity of participants, we have been very careful in choosing a cohort that is as uniform as possible before we performed the study. Thus, in this way, it is very important to point out that there are no significant differences between the groups of patients in relation to age, gender or between the number of days since the symptoms onset and samples collection. It is widely accepted that immune dysregulation contributes to the pathology seen in severe cases of SARS-CoV-2 infection. A consistent finding in many studies, including ours, is that COVID-19 patients display robust activation of the T cell pool, although a considerable portion of patients have minimal levels of activation compared to HC (Mathew et al., 2020). Our study shows that the frequency of activated T cells increases with the degree of severity of the disease. The frequency of activated memory, effectormemory and TEMRA CD4, CD8, DN, and even circulating TFH cells, is increased in patients with severe COVID-19. Furthermore, a very significant correlation was observed between many of these activated T cell subsets with severe disease while, as expected, an inverse association was observed with patients that experienced a mild disease. We also observed that CD4 and CD8 T cells from patients with severe disease tended to have higher levels of perforin. How ...

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 37, 39, 41, 43, 44 and 46. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

    About SciScore

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  3. Version published to 10.1101/2020.12.22.423917v1 on bioRxiv