Analysis of cell-mediated immunity in people with long COVID

  1. Nerea Montes
  2. Èlia Domènech
  3. Sílvia Guerrero
  4. Bárbara Oliván-Blázquez
  5. Rosa Magallón-Botaya

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Abstract

Introduction

The objective of this study is to analyse the specific immune response against SARS-CoV-2 in those affected by Long Covid (LC), attributable to T cells (cell-mediated immunity) and to carry out a parallel analysis of the humoral response and lymphocyte typing.

Methodology

Descriptive cross-sectional study of 74 patients with LC for at least 4 months since diagnosis. The collected data were: information on the COVID-19 episode and the persistent symptoms, medical history and a specific cell-mediated immunity to SARS-CoV-2 through flow cytometry, assessing the release of interferon-gamma (IFN-Ɣ) by T4 lymphocytes, T8 lymphocytes and NK cells. Descriptive and comparative analyses were carried out.

Results

Patients with LC had negative serology for Covid-19 in 89% of cases but 96% showed specific cellular immunity to SARS-CoV-2 an average of 9.5 months after infection: 89% of this response corresponded to T8 lymphocytes, 58% to NK cells, and 51% to T4 lymphocyte (20% negligibly positive). Most of them had altered immune cell typing and we found that T4 lymphocyte counts were low in 34% of cases and NK cell high in 64%. Macrophage populations were detected in the peripheral blood of 7% of them. Patients displayed a higher percentage of illnesses related to &[Prime]abnormal&[Prime] immune responses, either preceding SARS-CoV-2 infection (43%) or following it in 23% of cases.

Conclusion

The immune system appears to have an important involvement in the development of LC and viral persistence could be the cause or consequence of it. Further analysis with a control group should be performed.

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  1. Version published to 10.1101/2021.06.09.21258553v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.06.09.21258553: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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:
    This study has limitations and strengths. Its main strength is that it is an innovative study which aims to start/launch a research hypothesis for LC. However, there are also limitations: the principal limitation being the lack of a control group matched by age, sex and time passed since overcoming COVID-19, without presenting with persistent symptoms. Other limitations presented by this study are that the data analysed were gathered with a survey and the values of B lymphocytes and monocytes have not been provided by the laboratory in an independent manner. In addition, it is useful to note that the cellular response was recorded as being negative, positive and negligible (1-1.5%) or positive and significant (>1.5%) and it would be useful to quantify the value of IFN-gamma production by NK cells in response to SARS-CoV-2 compared to the NK cell baseline, this being a more non-specific innate response. This occurs only in group 4 which has 4 patients, and one of them has a specific antibody titre for SARS-CoV-2.

    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.
    • 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 10.1101/2021.06.09.21258553v1 on medRxiv