Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19
Open accessAbstract
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 CD14 Low CD16 High monocytes, accumulation of HLA-DR Low classical monocytes (Human Leukocyte Antigen - DR isotype), and release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10 Low CD101-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.
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Monocytes and neutrophils in severe COVID-19 patients expressed more genes involved in NF-κB signalling and ROS/NOS production throughout the disease course.
“monocytes and neutrophils in severe COVID-19 patients expressed more genes involved with NF-κB signaling and ROS/NOS production throughout the course of disease109.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [109]
Peripheral blood from mild COVID-19 patients contained more classical monocytes with an early and transient type I interferon signature.
“Peripheral blood of mild COVID-19 patients contained more classical monocytes (CD14+CD16−) exhibiting an early and transient type I IFN signature109,110.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [109]
HLA-DR expression on monocytes from severe COVID-19 patients is lower than on monocytes from mild patients.
“HLA-DR expression on monocytes from severe COVID-19 patients is also reduced relative to those from mild patients109,110,112,122.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [109]
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Local and systemic responses to SARS-CoV-2 infection in children and adults
Yoshida, M., Worlock, K. B., Huang, N., Lindeboom, R. G. H., Butler, C. R., Kumasaka, N., Dominguez Conde, C., Mamanova, L., Bolt, L., Richardson, L., et al. (2022) · Nature · doi:10.1038/s41586-021-04345-x · Cited by 365 · see citing works
Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection
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A blood atlas of COVID-19 defines hallmarks of disease severity and specificity
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Epigenetic memory of coronavirus infection in innate immune cells and their progenitors
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- Authors
- Silvin, A., Chapuis, N., Dunsmore, G., Goubet, A.-G., Dubuisson, A., Derosa, L., Almire, C., Hénon, C., Kosmider, O., Droin, N., Rameau, P., Catelain, C., Alfaro, A., Dussiau, C., Friedrich, C., Sourdeau, E., Marin, N., Szwebel, T.-A., Cantin, D., Mouthon, L., Borderie, D., Deloger, M., Bredel, D., Mouraud, S., Drubay, D., Andrieu, M., Lhonneur, A.-S., Saada, V., Stoclin, A., Willekens, C., Pommeret, F., Griscelli, F., Ng, L. G., Zhang, Z., Bost, P., Amit, I., Barlesi, F., Marabelle, A., Pène, F., Gachot, B., André, F., Zitvogel, L., Ginhoux, F., Fontenay, M., & Solary, E.
- Affiliations
- Inserm (FR)
- Centre National de la Recherche Scientifique (FR)
- Hôpital Cochin (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Institut Gustave Roussy (FR)
- Agency for Science, Technology and Research (SG)
- Southern University of Science and Technology (CN)
- Weizmann Institute of Science (IL)
- Corresponding author
- Ginhoux, Florent
- ORCID
- Silvin, Aymeric
- Chapuis, Nicolas
- Dunsmore, Garett
- Goubet, Anne-Gaëlle
- Dubuisson, Agathe
- Derosa, Lisa
- Almire, Carole
- Kosmider, Olivier
- Droin, Nathalie
- Rameau, Philippe
- Catelain, Cyril
- Alfaro, Alexia
- Dussiau, Charles
- Friedrich, Chloé
- Mouthon, Luc
- Borderie, Didier
- Deloger, Marc
- Bredel, Delphine
- Mouraud, Severine
- Drubay, Damien
- Andrieu, Muriel
- Saada, Véronique
- Stoclin, Annabelle
- Willekens, Christophe
- Pommeret, Fanny
- Griscelli, Frank
- Ng, Lai Guan
- Zhang, Zheng
- Bost, Pierre
- Amit, Ido
- Marabelle, Aurélien
- Pène, Frédéric
- André, Fabrice
- Zitvogel, Laurence
- Ginhoux, Florent
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 182
- Issue
- 6
- Pages
- 1401-1418.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7405878
- OpenAlex
- W3047168254
- Cited by
- 834
- References
- 71
- Citations by year
- 2026: 46 · 2025: 58 · 2024: 112 · 2023: 128 · 2022: 186 · 2021: 246 · 2020: 57
- FWCI
- 20.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc)
- HAL (submittedVersion)
- Funders
- Ligue Nationale Contre le Cancer (Equipes labellisées)
- Agence Nationale de la Recherche (IHU PRISM)
- Institut National du Cancer (SIRIC CARPEM, SOCRATE)
- Fondation ARC
- Fondation pour la Recherche Médicale
- Dassault Systems
- Agnes B
- Izipizi
- Ralph Lauren
- Malakoff Humanis
- Singapore Immunology Network
- Singapore National Research Foundation (NRF2016NRF-NRFI001-02)
- European Molecular Biology Organization
- SIgN
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- COVID-19 pandemic, SARS-CoV-2, disease severity, calprotectin, S100A8/S100A9, myeloid cells, non-classical monocytes, classical monocytes, emergency myelopoiesis, innate immunity, prognostic factors, peripheral blood
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Flow Cytometry, Humans, Monocytes, Pneumonia, Viral, Prospective Studies, Coronavirus, Coronavirus Infections, Myeloid Cells, Leukocyte L1 Antigen Complex, Pandemics
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