Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19

Cell. 2020 Sep 17;182(6):1401-1418.e18. doi: 10.1016/j.cell.2020.08.002. Epub 2020 Aug 5.


Blood myeloid cells are known to be dysregulated in coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate immunity discriminate high-risk patients. Thus, we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14LowCD16High monocytes, accumulation of HLA-DRLow classical monocytes (Human Leukocyte Antigen - DR isotype), and release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101-CXCR4+/- neutrophils with an immunosuppressive profile accumulated in the blood and lungs, suggesting emergency myelopoiesis. Finally, we show that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe form of COVID-19, suggesting a predictive value that deserves prospective evaluation.

Keywords: COVID-19; S100A8; S100A9; SARS-CoV-2; calprotectin; emergency myelopoiesis; monocyte subsets; neutrophils; type I interferon.

MeSH terms

  • Betacoronavirus
  • COVID-19
  • Coronavirus Infections*
  • Coronavirus*
  • Flow Cytometry
  • Humans
  • Leukocyte L1 Antigen Complex
  • Monocytes
  • Myeloid Cells
  • Pandemics*
  • Pneumonia, Viral*
  • Prospective Studies
  • SARS-CoV-2


  • Leukocyte L1 Antigen Complex