Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild to disease

Immunophenotyping, RNA sequence and serum cytokine analyses using blood samples from COVID-19 patients with a range of disease severity for over 12 weeks from disease onset reveals that an early robust bystander CD8+ T cell immune response without systemic inflammation is correlated with asymptomatic or mild diseases. Hospitalized patients with severe disease had delayed bystander CD8+ T cell response and systemic inflammation. Bystander CD8+ T cells involves activation of memory CD8+ T cells independent of TCR stimulation, driven by type I IFN. Immune cell abnormalities correlated with altered inflammatory responses, with signature associated with increased oxidative phosphorylation often persist for weeks to months after SARS-CoV-2 infection.