Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease
Laura Bergamaschi, Federica Mescia, Lorinda Turner, Aimee Hanson, Prasanti Kotagiri, Benjamin J. Dunmore, Hélène Ruffieux, Aloka De, Oisín Huhn, Michael D. Morgan, Pehuén Pereyra Gerber, Mark R. Wills, Stephen Baker, Fernando J. Calero‐Nieto, Rainer Döffinger, Gordon Dougan, Anne Elmer, Ian Goodfellow, Ravindra K. Gupta, Myra Hosmillo, Kelvin Hunter, Nathalie Kingston, Paul J. Lehner, Nicholas J. Matheson, Jeremy K. Nicholson, Anna M. Petrunkina, Sylvia Richardson, Caroline Saunders, James Thaventhiran, Erik J. M. Toonen, Michael P. Weekes, Berthold Göttgens, Mark Toshner, Christoph Hess, John R. Bradley, Paul Lyons, Kenneth G. C. Smith
Abstract
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.