Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease.

L. Bergamaschi; F. Mescia; L. Turner; A.L. Hanson; P. Kotagiri; B.J. Dunmore; H. Ruffieux; A. De Sa; O. Huhn; M.D. Morgan; P.P. Gerber; M.R. Wills; S. Baker; F. J. Calero‐Nieto; R. Doffinger; G. Dougan; A. Elmer; I.G. Goodfellow; R.K. Gupta; M. Hosmillo; K. Hunter; N. Kingston; P.J. Lehner; N.J. Matheson; J.K. Nicholson; A.M. Petrunkina; S. Richardson; C. Saunders; J.E.D. Thaventhiran; E.J.M. Toonen; M.P. Weekes; B. Göttgens; M. Toshner; C. Hess; J.R. Bradley; P.A. Lyons; K.G.C. Smith

doi:10.1016/j.immuni.2021.05.010

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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.

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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.

L. Bergamaschi, F. Mescia, L. Turner, A.L. Hanson, P. Kotagiri, B.J. Dunmore, H. Ruffieux, A. De Sa, O. Huhn, M.D. Morgan, …

Immunity, Vol.54(6), pp.1257-1275.e8

2021

DOI: https://doi.org/10.1016/j.immuni.2021.05.010

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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+ 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.

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Title: Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease.
Authors/Creators: L. Bergamaschi (Author/Creator) - Addenbrooke's Hospital
F. Mescia (Author/Creator) - Addenbrooke's Hospital
L. Turner (Author/Creator) - Addenbrooke's Hospital
A.L. Hanson (Author/Creator) - Addenbrooke's Hospital
P. Kotagiri (Author/Creator) - Addenbrooke's Hospital
B.J. Dunmore (Author/Creator) - Addenbrooke's Hospital
H. Ruffieux (Author/Creator) - MRC Biostatistics Unit
A. De Sa (Author/Creator) - Addenbrooke's Hospital
O. Huhn (Author/Creator) - Addenbrooke's Hospital
M.D. Morgan (Author/Creator) - European Bioinformatics Institute
P.P. Gerber (Author/Creator) - Addenbrooke's Hospital
M.R. Wills (Author/Creator) - Addenbrooke's Hospital
S. Baker (Author/Creator) - Addenbrooke's Hospital
F. J. Calero‐Nieto (Author/Creator)
R. Doffinger (Author/Creator) - Addenbrooke's Hospital
G. Dougan (Author/Creator) - Addenbrooke's Hospital
A. Elmer (Author/Creator) - Cambridge University Hospitals NHS Foundation Trust
I.G. Goodfellow (Author/Creator) - Addenbrooke's Hospital
R.K. Gupta (Author/Creator) - Addenbrooke's Hospital
M. Hosmillo (Author/Creator) - Addenbrooke's Hospital
K. Hunter (Author/Creator) - Addenbrooke's Hospital
N. Kingston (Author/Creator) - Cambridge University Hospitals NHS Foundation Trust
P.J. Lehner (Author/Creator) - Addenbrooke's Hospital
N.J. Matheson (Author/Creator) - Addenbrooke's Hospital
J.K. Nicholson (Author/Creator) - Murdoch University
A.M. Petrunkina (Author/Creator) - Addenbrooke's Hospital
S. Richardson (Author/Creator) - MRC Biostatistics Unit
C. Saunders (Author/Creator) - Cambridge University Hospitals NHS Foundation Trust
J.E.D. Thaventhiran (Author/Creator)
E.J.M. Toonen (Author/Creator) - Hycult Biotech (Netherlands)
M.P. Weekes (Author/Creator) - University of Cambridge
B. Göttgens (Author/Creator) - Wellcome/MRC Cambridge Stem Cell Institute
M. Toshner (Author/Creator) - Papworth Hospital NHS Foundation Trust
C. Hess (Author/Creator) - University of Cambridge
J.R. Bradley (Author/Creator) - Cambridge University Hospitals NHS Foundation Trust
P.A. Lyons (Author/Creator) - Addenbrooke's Hospital
K.G.C. Smith (Author/Creator) - Addenbrooke's Hospital
Publication Details: Immunity, Vol.54(6), pp.1257-1275.e8
Publisher: Cell Press/Elsevier
Identifiers: 991005544569807891
Copyright: © 2021 Published by Elsevier Inc.
Murdoch Affiliation: Health Futures Institute
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.104 Virology - General; 1.104.1353 Coronavirus Research
Web Of Science research areas: Immunology
ESI research areas: Immunology