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Corticosteroid treatment in COVID-19 modulates host inflammatory responses and transcriptional signatures of immune dysregulation.

Authors
  • Pinski, Amanda N1, 2, 3
  • Steffen, Tara L4
  • Zulu, Michael Z1, 2, 3
  • George, Sarah L5
  • Dickson, Alexandria4
  • Tifrea, Delia6
  • Maroney, Kevin J1
  • Tedeschi, Neil7
  • Zhang, Yun7
  • Scheuermann, Richard H7
  • Pinto, Amelia K4
  • Brien, James D4
  • Messaoudi, Ilhem1, 2, 3
  • 1 Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, USA.
  • 2 Center for Virus Research, University of California, Irvine, Irvine, California, USA.
  • 3 Institute for Immunology, University of California, Irvine, California, USA.
  • 4 Department of Molecular Microbiology and Immunology, Saint Louis University, St Louis, Missouri, USA.
  • 5 Department of Medicine, Division of Infectious Diseases, Saint Louis University, St Louis, Missouri, USA.
  • 6 Department of Pathology and Laboratory Medicine, University of California, Irvine, California, USA.
  • 7 J. Craig Venter Institute, La Jolla, California, USA.
Type
Published Article
Journal
Journal of Leukocyte Biology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Dec 01, 2021
Volume
110
Issue
6
Pages
1225–1239
Identifiers
DOI: 10.1002/JLB.4COVA0121-084RR
PMID: 34730254
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-2019 (COVID-19), a respiratory disease that varies in severity from mild to severe/fatal. Several risk factors for severe disease have been identified, notably age, male sex, and pre-existing conditions such as diabetes, obesity, and hypertension. Several advancements in clinical care have been achieved over the past year, including the use of corticosteroids (e.g., corticosteroids) and other immune-modulatory treatments that have now become standard of care for patients with acute severe COVID-19. While the understanding of the mechanisms that underlie increased disease severity with age has improved over the past few months, it remains incomplete. Furthermore, the molecular impact of corticosteroid treatment on host response to acute SARS-CoV-2 infection has not been investigated. In this study, a cross-sectional and longitudinal analysis of Ab, soluble immune mediators, and transcriptional responses in young (65 ≤ years) and aged (≥ 65 years) diabetic males with obesity hospitalized with acute severe COVID-19 was conducted. Additionally, the transcriptional profiles in samples obtained before and after corticosteroids became standard of care were compared. The analysis indicates that severe COVID-19 is characterized by robust Ab responses, heightened systemic inflammation, increased expression of genes related to inflammatory and pro-apoptotic processes, and reduced expression of those important for adaptive immunity regardless of age. In contrast, COVID-19 patients receiving steroids did not show high levels of systemic immune mediators and lacked transcriptional indicators of heightened inflammatory and apoptotic responses. Overall, these data suggest that inflammation and cell death are key drivers of severe COVID-19 pathogenesis in the absence of corticosteroid therapy. ©2021 Society for Leukocyte Biology.

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