@article{Bergamaschi_L-2021_119615,
title = {Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease},
author = {Bergamaschi, L. and Mescia, F. and Turner, L. and Hanson, A. and Kotagiri, P. and Dunmore, B. and Ruffieux, H. and Sa, A. and Huhn, O. and Morgan, M. and Gerber, P. and Wills, M. and Baker, S. and Calero-Nieto, F. and Doffinger, R. and Dougan, G. and Elmer, A. and Goodfellow, I. and Gupta, R. and Hosmillo, M. and Hunter, K. and Kingston, N. and Lehner, P. and Matheson, N. and Nicholson, J. and Petrunkina, A. and Richardson, S. and Saunders, C. and Thaventhiran, J. and Toonen, E. and Weekes, M. and Göttgens, B. and Toshner, M. and Hess, C. and Bradley, J. and Lyons, P. and Smith, K.},
month = {may},
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+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.},
pages = {1257-1275},
volume = {54},
issue = {6},
journal = {Immunity},
publisher = {Elsevier},
url = {https://doi.org/10.1016/j.immuni.2021.05.010},
}
