A possible role of immunopathogenesis in COVID-19 progression

  1. Moritz Anft
  2. Krystallenia Paniskaki
  3. Arturo Blazquez-Navarro
  4. Adrian Doevelaar
  5. Felix S. Seibert
  6. Bodo Hoelzer
  7. Sarah Skrzypczyk
  8. Eva Kohut
  9. Julia Kurek
  10. Jan Zapka
  11. Patrizia Wehler
  12. Sviatlana Kaliszczyk
  13. Sharon Bajda
  14. Constantin J. Thieme
  15. Toralf Roch
  16. Margarethe Justine Konik
  17. Thorsten Brenner
  18. Clemens Tempfer
  19. Carsten Watzl
  20. Sebastian Dolff
  21. Ulf Dittmer
  22. Timm H. Westhoff
  23. Oliver Witzke
  24. Ulrik Stervbo
  25. Nina Babel

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Abstract

Background

The efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities.

Methods

In this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity.

Results

Significantly diminished frequencies of CD8 + T-cells, CD4 + and CD8 + T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4 + frequencies underscore the role of specific immunity in disease progression.

Conclusion

Our data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.28.20083089: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study approval: The study was approved by the ethical committee of the Ruhr-University Bochum (20-6886) and University Hospital Essen (20-9214-BO)
    Consent: Written informed consent was obtained from all participants.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableMost patients in the critical groups were males.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistics: Flow cytometry data were analyzed using FlowJo version 10.6.2 (BD Biosciences); gating strategies are presented in Fig. S5-S9.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    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: 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.
    • Thank you for including a protocol registration statement.

    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 10.1101/2020.04.28.20083089v2 on medRxiv
  3. Version published to 10.1101/2020.04.28.20083089v1 on medRxiv