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

Mudd, Philip A.; Crawford, Jeremy Chase; Turner, Jackson S.; Souquette, Aisha; Reynolds, Daniel; Bender, Diane; Bosanquet, James P.; Anand, Nitin J.; Striker, David A.; Martin, R. Scott; Boon, Adrianus C. M.; House, Stacey L.; Remy, Kenneth E.; Hotchkiss, Richard S.; Presti, Rachel M.; O’Halloran, Jane A.; Powderly, William G.; Thomas, Paul G.; Ellebedy, Ali H.

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.