Cell
Volume 182, Issue 6, 17 September 2020, Pages 1401-1418.e18
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Article
Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19

https://doi.org/10.1016/j.cell.2020.08.002Get rights and content
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Highlights

  • Patients with severe COVID-19 accumulate HLA-DRLow monocytes and immature neutrophils in blood/lungs

  • Calprotectin level positively correlates with neutrophil count and disease severity

  • Loss of non-classical monocytes could identify high risk of severe COVID-19

Summary

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 CD10LowCD101CXCR4+/− 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
calprotectin
emergency myelopoiesis
monocyte subsets
neutrophils
S100A8
S100A9
SARS-CoV-2
type I interferon

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These authors contributed equally

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