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 implication