Summary SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18, and IL-10 and broad activation marked by the upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3 + cT FH 1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralization activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, and IL-18, and hyperactivation of innate, adaptive, and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies. Graphical abstract Highlights Analyses of 184 immune features define kinetics of immune responses to SARS-CoV-2 Circulating T FH 1 cells in acute COVID-19 correlate with antibodies sIL-6R levels are elevated in severe COVID-19 but do not correlate with IL-6 Elevated IL-6 and IL-18 correlate with immune cell hyperactivation Koutsakos et al. perform a broad analysis of 184 immune features using blood samples from 85 COVID-19 cases across time and severity groups. The study defines circulating T FH 1 cells as a correlate of antibody responses and sIL-6R, IL-6, and IL-18 as correlates of disease severity.
【저자키워드】 SARS-CoV-2, IL-6, HLA-DR, CD38, T follicular helper cells, antibody-secreting cells, acute COVID-19, IL-18, convalescent COVID-19, soluble IL-6 receptor,