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Mazer MB, Davitt E, Turnbull IR, et al. In Vitro-Administered Dexamethasone Suppresses T Cell Function With Reversal by Interleukin-7 in Coronavirus Disease 2019. Crit Care Explor. 2021;3(4):e0378doi: 10.1097/CCE.0000000000000378.
Mazer, M. B., Davitt, E., Turnbull, I. R., Caldwell, C. C., Brakenridge, S. C., Remy, K. E., & Hotchkiss, R. S. (2021). In Vitro-Administered Dexamethasone Suppresses T Cell Function With Reversal by Interleukin-7 in Coronavirus Disease 2019. Critical care explorations, 3(4), e0378. https://doi.org/10.1097/CCE.0000000000000378
Mazer, Monty B, et al. "In Vitro-Administered Dexamethasone Suppresses T Cell Function With Reversal by Interleukin-7 in Coronavirus Disease 2019." Critical care explorations vol. 3,4 (2021): e0378. doi: https://doi.org/10.1097/CCE.0000000000000378
Mazer MB, Davitt E, Turnbull IR, Caldwell CC, Brakenridge SC, Remy KE, Hotchkiss RS. In Vitro-Administered Dexamethasone Suppresses T Cell Function With Reversal by Interleukin-7 in Coronavirus Disease 2019. Crit Care Explor. 2021 Apr 02;3(4):e0378. doi: 10.1097/CCE.0000000000000378. eCollection 2021 Apr. PMID: 33834168; PMCID: PMC8021361.
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Crit Care Explor. 2021 Apr 02;3(4):e0378. doi: 10.1097/CCE.0000000000000378. eCollection 2021 Apr.

In Vitro-Administered Dexamethasone Suppresses T Cell Function With Reversal by Interleukin-7 in Coronavirus Disease 2019.

Critical care explorations

Monty B Mazer, Ethan Davitt, Isaiah R Turnbull, Charles C Caldwell, Scott C Brakenridge, Kenneth E Remy, Richard S Hotchkiss

Affiliations

  1. Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO.
  2. Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
  3. Department of Surgery, Washington University School of Medicine, St. Louis, MO.
  4. Division of Research, Department of Surgery, University of Cincinnati, Cincinnati, OH.
  5. Department of Surgery, University of Florida College of Medicine, Gainesville, FL.
  6. Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.

PMID: 33834168 PMCID: PMC8021361 DOI: 10.1097/CCE.0000000000000378

Abstract

OBJECTIVES: Corticosteroid therapy has become standard of care therapy for hospitalized patients infected with the severe acute respiratory syndrome coronavirus-2 global pandemic-causing virus. Whereas systemic inflammation is a notably important feature in coronavirus disease 2019 pathogenesis, adaptive immune suppression and the inability to eradicate effectively the virus remain significant factors as well. We sought to evaluate the in vitro effects of dexamethasone phosphate on T cell function in peripheral blood mononuclear cells derived from patients with acute, severe, and moderate coronavirus disease 2019.

DESIGN: Prospective in vitro laboratory study.

SETTING: Coronavirus disease 2019-specific medical wards and ICUs at a single-center, quaternary-care academic hospital between October 1, 2020, and November 15, 2020.

PATIENTS: Eleven patients diagnosed with coronavirus disease 2019 admitted to either the ICU or hospital coronavirus disease 2019 unit. Three patients had received at least one dose of dexamethasone prior to enrollment.

INTERVENTIONS: Fresh whole blood was collected, and peripheral blood mononuclear cells were immediately isolated and plated onto precoated enzyme-linked immunospot plates for detection of interferon-γ production. Samples were incubated with CD3/CD28 antibodies alone and with three concentrations of dexamethasone. These conditions were also stimulated with recombinant human interleukin-7. Following overnight incubation, the plates were washed and stained for analysis using Cellular Technology Limited ImmunoSpot S6 universal analyzer (ImmunoSpot by Cellular Technology Limited, Cleveland, OH).

MEASUREMENTS AND MAIN RESULTS: Functional cytokine production was assessed by quantitation of cell spot number and total well intensity after calculation for each enzyme-linked immunospot well using the Cellular Technology Limited ImmunoSpot Version 7.0 professional software (CTL Analyzers, Shaker Heights, OH). Comparisons were made using

CONCLUSIONS: Further evaluation of the effect of immunomodulatory therapies is warranted in coronavirus disease 2019. A refined functional, precision medicine approach that evaluates the cellular immune function of individual patients with coronavirus disease 2019 is needed to better define which therapies could have benefit or cause harm for specific patients.

Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.

Keywords: coronavirus disease 2019; corticosteroids; cytokine storm; dexamethasone; immunosuppression

Conflict of interest statement

The authors have disclosed that they do not have any potential conflicts of interest.

References

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