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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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Bergamaschi, Laura 
Turner, Lorinda 
Hanson, Aimee L 
Kotagiri, Prasanti 


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



COVID-19, SARS-CoV-2, TNF-α, bystander CD8+ T cell, complement, immune pathology, interferon, recovery, systemic inflammation, Biomarkers, CD8-Positive T-Lymphocytes, COVID-19, Cytokines, Disease Susceptibility, Gene Expression Profiling, Host-Pathogen Interactions, Humans, Inflammation Mediators, Longitudinal Studies, Lymphocyte Activation, Oxidative Phosphorylation, Phenotype, Prognosis, Reactive Oxygen Species, SARS-CoV-2, Severity of Illness Index, Transcriptome

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Elsevier BV
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (084957/Z/08/Z)
Wellcome Trust (108070/Z/15/Z)
Wellcome Trust (200871/Z/16/Z)
Medical Research Council (MR/P008801/1)
Wellcome Trust (207498/Z/17/Z)
MRC (MR/V011561/1)
Medical Research Council (MR/S036113/1)
Medical Research Council (MC_PC_17230)
Medical Research Council (MR/S00081X/1)
MRC (MR/W014556/1)
MRC (via University of Birmingham) (MR/V028448/1)
Wellcome Trust (210688/Z/18/Z)
Wellcome Trust (209749/Z/17/Z)
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