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Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease.
- Source :
-
Immunity [Immunity] 2021 Jun 08; Vol. 54 (6), pp. 1257-1275.e8. Date of Electronic Publication: 2021 May 16. - Publication Year :
- 2021
-
Abstract
- The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8 <superscript>+</superscript> T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications.<br />Competing Interests: Declaration of interests The authors declare they have no competing interests. E.J.M. Toonen is an employee of Hycult Biotechnology b.v.<br /> (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Biomarkers
CD8-Positive T-Lymphocytes metabolism
COVID-19 diagnosis
COVID-19 genetics
Cytokines metabolism
Disease Susceptibility
Gene Expression Profiling
Humans
Inflammation Mediators metabolism
Longitudinal Studies
Lymphocyte Activation genetics
Oxidative Phosphorylation
Phenotype
Prognosis
Reactive Oxygen Species metabolism
Severity of Illness Index
Transcriptome
CD8-Positive T-Lymphocytes immunology
COVID-19 immunology
COVID-19 virology
Host-Pathogen Interactions immunology
Lymphocyte Activation immunology
SARS-CoV-2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 54
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 34051148
- Full Text :
- https://doi.org/10.1016/j.immuni.2021.05.010