Summary 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. Graphical abstract Highlights • Longitudinal analysis of COVID-19 patients with a range of disease severity • Early bystander CD8 + T cell and plasmablast responses characterize mild disease • Pronounced systemic inflammation evident at first presentation in more severe COVID-19 • Immune/inflammatory abnormalities persist in severe disease to 60 days post symptoms The immune changes that underlie COVID-19 severity have not been fully defined. By analyzing a longitudinal cohort of COVID-19 patients and integrating inflammatory factors, immunophenotyping, and transcriptome data, Bergamaschi et al. identify both early and persistent immune changes that distinguish mild and/or asymptomatic from more severe disease.
【저자키워드】 COVID-19, SARS-CoV-2, interferon, complement, recovery, TNF-α, systemic inflammation, bystander CD8+ T cell, immune pathology, 【초록키워드】 Transcriptome, Necrosis, Tumor, immune response, Cytokines, severe COVID-19, Inflammatory responses, severity, disease severity, COVID-19 severity, cytokine, Symptom, immunopathology, CD8, inflammatory factors, Kinetics, Cohort, T cell, Immunophenotyping, interleukin, tumor necrosis factor, Viral, Asymptomatic, Viral load, response, RNA sequencing, Mild, systemic inflammation, group, longitudinal, disease, COVID-19 patients, Mild disease, longitudinal analysis, TNF, cellular, Analysis, severe disease, COVID-19 patient, in some, tumor necrosis, symptom onset, bystander, Abstract, infected individuals, individual, complex, plasmablast responses, serum cytokine, disease severities, pathological response, abnormality, immune changes, clinical implications, oxidative phosphorylation, robust, defined, analyzed, identify, subsequent, characterized, individuals, driven by, underlie, replacing, immune change, immune defect, plasmablast response, 【제목키워드】 pathology, severe COVID-19, immune, Mild, longitudinal, disease, Analysis, bystander, Activation, CD8+, reveal,