Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm

Sci Adv. 2020 Dec 9;6(50):eabe3024. doi: 10.1126/sciadv.abe3024. Print 2020 Dec.


We pursued a study of immune responses in coronavirus disease 2019 (COVID-19) and influenza patients. Compared to patients with influenza, patients with COVID-19 exhibited largely equivalent lymphocyte counts, fewer monocytes, and lower surface human leukocyte antigen (HLA)-class II expression on selected monocyte populations. Furthermore, decreased HLA-DR on intermediate monocytes predicted severe COVID-19 disease. In contrast to prevailing assumptions, very few (7 of 168) patients with COVID-19 exhibited cytokine profiles indicative of cytokine storm syndrome. After controlling for multiple factors including age and sample time point, patients with COVID-19 exhibited lower cytokine levels than patients with influenza. Up-regulation of IL-6, G-CSF, IL-1RA, and MCP1 predicted death in patients with COVID-19 but were not statistically higher than patients with influenza. Single-cell transcriptional profiling revealed profound suppression of interferon signaling among patients with COVID-19. When considered across the spectrum of peripheral immune profiles, patients with COVID-19 are less inflamed than patients with influenza.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • COVID-19 / diagnosis
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • Cells, Cultured
  • Cytokine Release Syndrome / genetics
  • Cytokine Release Syndrome / immunology*
  • Cytokine Release Syndrome / metabolism
  • Cytokines / genetics
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Diagnosis, Differential
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology*
  • Influenza, Human / diagnosis
  • Influenza, Human / genetics
  • Influenza, Human / immunology*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Young Adult


  • Cytokines