SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells

  1. Yogesh Singh
  2. Christoph Trautwein
  3. Rolf Fendel
  4. Naomi Krickeberg
  5. Georgy Berezhnoy
  6. Rosi Bissinger
  7. Stephan Ossowski
  8. Madhuri S. Salker
  9. Nicolas Casadei
  10. Olaf Riess
  11. the Deutsche COVID-19 OMICS Initiative (DeCOI)

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

The SARS-CoV-2 virus is the causative agent of the global COVID-19 infectious disease outbreak, which can lead to acute respiratory distress syndrome (ARDS). However, it is still unclear how the virus interferes with immune cell and metabolic functions in the human body. In this study, we investigated the immune response in acute or convalescent COVID19 patients. We characterized the peripheral blood mononuclear cells (PBMCs) using flow cytometry and found that CD8 + T cells were significantly subsided in moderate COVID-19 and convalescent patients. Furthermore, characterization of CD8 + T cells suggested that patients with a mild and moderate course of the COVID-19 disease and convalescent patients have significantly diminished expression of both perforin and granzyme A in CD8 + T cells. Using 1 H-NMR spectroscopy, we characterized the metabolic status of their autologous PBMCs. We found that fructose, lactate and taurine levels were elevated in infected (mild and moderate) patients compared with control and convalescent patients. Glucose, glutamate, formate and acetate levels were attenuated in COVID-19 (mild and moderate) patients. In summary, our report suggests that SARS-CoV-2 infection leads to disrupted CD8 + T cytotoxic functions and changes the overall metabolic functions of immune cells.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.09.04.282780: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics statement: The study protocols were approved by the University of Tübingen, Germany Human Research Ethics Committee (
    Consent: All participants provided written informed consent in accordance with the Declaration of Helsinki.
    RandomizationBlood was collected from COVID-19 patients enrolled into two different prospective randomized, placebo-controlled, double blind clinical trials evaluating safety and efficacy of hydroxychloroquine in COVID-19 outpatients (COMIHIY) and hospitalized patients (COV-HCQ).
    BlindingBlood was collected from COVID-19 patients enrolled into two different prospective randomized, placebo-controlled, double blind clinical trials evaluating safety and efficacy of hydroxychloroquine in COVID-19 outpatients (COMIHIY) and hospitalized patients (COV-HCQ).
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Amongst this cohort, 3 persons reported mild fever for 10-11 days and 1 individual reported no fever but found positive for SARS-CoV-2 antibodies.
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analysed using Flow Jo (Tree Star) and fluorescence minus one controls (FMO) were used for setting up the arbitrary gates for the major cell markers.
    Flow Jo
    suggested: (FlowJo, RRID:SCR_008520)
    FACS data were analysed using one-way ANOVA for multiple group comparisons (mild, moderate, convalescent and HC) in GraphPad Prism software.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Metabolites data were analysed with MetaboAnalyst 4.0 software.
    MetaboAnalyst
    suggested: (MetaboAnalyst, RRID:SCR_015539)

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

    IdentifierStatusTitle
    NCT04340544TerminatedHydroxychloroquine for the Treatment of Mild COVID-19 Diseas…
    NCT04342221RecruitingHydroxychloroquine for COVID-19

    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.

    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.

  2. Version published to 10.1101/2020.09.04.282780 on bioRxiv