TY - JOUR
AU - Bergamaschi, Laura
AU - Mescia, Federica
AU - Turner, Lorinda
AU - Hanson, Aimee L.
AU - Kotagiri, Prasanti
AU - Dunmore, Benjamin J.
AU - Ruffieux, Hélène
AU - Sa, Aloka De
AU - Huhn, Oisín
AU - Morgan, Michael D.
AU - Gerber, Pehuén Pereyra
AU - Wills, Mark R.
AU - Baker, Stephen
AU - Calero-Nieto, Fernando J.
AU - Doffinger, Rainer
AU - Dougan, Gordon
AU - Elmer, Anne
AU - Goodfellow, Ian G.
AU - Gupta, Ravindra K.
AU - Hosmillo, Myra
AU - Hunter, Kelvin
AU - Kingston, Nathalie
AU - Lehner, Paul J.
AU - Matheson, Nicholas J.
AU - Nicholson, Jeremy K.
AU - Petrunkina, Anna M.
AU - Richardson, Sylvia
AU - Saunders, Caroline
AU - Thaventhiran, James E.D.
AU - Toonen, Erik J.M.
AU - Weekes, Michael P.
AU - Göttgens, Berthold
AU - Toshner, Mark
AU - Hess, Christoph
AU - Bradley, John R.
AU - Lyons, Paul A.
AU - Smith, Kenneth G.C.
PY - 2021
DA - May
TI - Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease
JO - Immunity
EP - 1275
VL - 54
IS - 6
DO - https://doi.org/10.1016/j.immuni.2021.05.010
AB - 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.
PB - Elsevier
UR - https://hdl.handle.net/2164/20265
KW - Coronavirus (COVID-19)
ER