Integrated immune dynamics define correlates of COVID-19 severity and antibody responses

Cell Rep Med. 2021 Mar 16;2(3):100208. doi: 10.1016/j.xcrm.2021.100208. Epub 2021 Feb 5.


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+cTFH1 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.

Keywords: CD38; HLA-DR; IL-18; IL-6; SARS-CoV-2; T follicular helper cells; acute COVID-19; antibody-secreting cells; convalescent COVID-19; soluble IL-6 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antibody Formation*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Female
  • Humans
  • Immunity, Innate
  • Interleukin-18 / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Receptors, CXCR3 / metabolism
  • Receptors, Interleukin-6 / metabolism
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / isolation & purification
  • Severity of Illness Index
  • Th1 Cells / cytology
  • Th1 Cells / metabolism
  • Young Adult


  • Antibodies, Viral
  • CXCR3 protein, human
  • Interleukin-18
  • Interleukin-6
  • Receptors, CXCR3
  • Receptors, Interleukin-6