Related Experiment Video
Updated: Dec 11, 2025
The Isolation and Characterization of Low- and Normal- Density Neutrophils from Whole Blood
Published on: February 7, 2025
Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19
Aymeric Silvin1, Nicolas Chapuis2, Garett Dunsmore1
1INSERM U1015, Gustave Roussy Cancer Campus, Villejuif 94800, France.
Insights
Severe COVID-19 involves myeloid cell changes like monocyte depletion and immature neutrophils. Calprotectin levels and monocyte counts may predict severe disease, aiding early risk assessment.
Area of Science:
- Immunology
- Hematology
- Virology
Background:
- Dysregulation of blood myeloid cells is observed in COVID-19.
- The relationship between innate myeloid response, disease severity, and high-risk patient discrimination in COVID-19 remains unclear.
Purpose of the Study:
- To investigate differences in innate myeloid cell response based on COVID-19 severity.
- To determine if innate immunity markers can identify high-risk COVID-19 patients.
Main Methods:
- High-dimensional flow cytometry and single-cell RNA sequencing were used on peripheral blood cells from COVID-19 patients.
- Analysis focused on monocyte and neutrophil populations and their associated markers.
Main Results:
- Severe COVID-19 cases showed decreased non-classical monocytes (CD14LowCD16High) and accumulated HLA-DRLow classical monocytes.
- Massive calprotectin release (S100A8/S100A9) and immature, immunosuppressive neutrophils (CD10LowCD101-CXCR4+/-) were detected in severe cases, suggesting emergency myelopoiesis.
- Calprotectin plasma levels and reduced non-classical monocyte frequencies could distinguish severe COVID-19 patients.
Conclusions:
- Specific alterations in myeloid cell populations and calprotectin levels characterize severe COVID-19.
- Calprotectin and monocyte frequency show potential as predictive biomarkers for severe COVID-19, warranting further prospective studies.
Abstract:
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.
