TY - JOUR
T1 - Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19
AU - Silvin, Aymeric
AU - Chapuis, Nicolas
AU - Dunsmore, Garett
AU - Goubet, Anne-Gaelle
AU - Dubuisson, Agathe
AU - Derosa, Lisa
AU - Almire, Carole
AU - Henon, Clemence
AU - Kosmider, Olivier
AU - Droin, Nathalie
AU - Rameau, Philippe
AU - Catelain, Cyril
AU - Alfaro, Alexia
AU - Dussiau, Charles
AU - Friedrich, Chloe
AU - Sourdeau, Elise
AU - Marin, Nathalie
AU - Szwebel, Tali-Anne
AU - Cantin, Delphine
AU - Mouthon, Luc
AU - Borderie, Didier
AU - Deloger, Marc
AU - Bredel, Delphine
AU - Mouraud, Severine
AU - Drubay, Damien
AU - Andrieu, Muriel
AU - Lhonneur, Anne-Sophie
AU - Saada, Veronique
AU - Stoclin, Annabelle
AU - Willekens, Christophe
AU - Pommeret, Fanny
AU - Griscelli, Frank
AU - Ng, Lai Guan
AU - Zhang, Zheng
AU - Bost, Pierre
AU - Amit, Ido
AU - Barlesi, Fabrice
AU - Marabelle, Aurelien
AU - Pene, Frederic
AU - Gachot, Bertrand
AU - Andre, Fabrice
AU - Zitvogel, Laurence
AU - Ginhoux, Florent
AU - Fontenay, Michaela
AU - Solary, Eric
N1 - Our teams are supported by grants from Ligue Nationale Contre le Cancer (Equipes labellisées), Agence Nationale de la Recherche (IHU PRISM), Institut National du Cancer (SIRIC CARPEM and SOCRATE), Fondation ARC, Fondation pour la Recherche Médicale, and private donations (Dassault Systems, Agnes B, Izipizi, Ralph Lauren, and Malakoff Humanis) as well as Fondation Gustave Roussy (including the Paediatric Campaign). F.G. is supported by Singapore Immunology Network (SIgN) core funding and Singapore National Research Foundation Senior Investigatorship (NRFI) NRF2016NRF-NRFI001-02 and is a European Molecular Biology Organization (EMBO) YIP awardee. L.G.N. is supported by SIgN core funding. We thank Emmanuelle Gallois, Jean-François Méritet, and Flore Rosenberg for SARS-CoV-2 PCR tests and the following individuals for technical support: Jean-Daniel Chiche and Jean-Paul Mira (Medical Intensive Care Unit, Cochin Hospital); Maela Francillette, Betty Leite, and Valérie Camara-Clayette (AMMICa platforms, CRB, Gustave Roussy); Audrey Naimo (AMMICa platforms, Gustave Roussy); Karine Bailly (CYBIO platform, Institut Cochin); and Jérôme Duchemin, Catherine Gicquel, Amandine Houvert, Georges Jourdi, Françoise Levavasseur, Laurence Marnet, Bruno Montout, Loetitia Rhino, Isabelle Souville, and Christine Scamps. We also thank Julien Hadoux and Jean-Marie Michot for providing samples, Dorothée Selimoglu-Buet and Xavier Mariette for helpful scientific discussions, and Dr. Lucy Robinson (Insight Editing London) for editing the manuscript. Author contributions - Conceptualization, A. Silvin, N.C., F. Ginhoux, M.F., and E. Solary; Methodology, L.G.N., I.A., Z.Z., L.Z., and B.G.; Investigation, G.D., A.-G.G., A.D., C.A., C.H., O.K., N.D., P.R., C.C., C.D., C.F., D.C., D. Bredel, S.M., M.A., A.-S.L., V.S., F. Griscelli, and P.B.; Formal Analysis, N.C., G.D., A.A., D. Borderie, M.D., and D.D.; Funding Acquisition, A.M., F.A., L.Z., F. Ginhoux, M.F., and E. Solary; Resources, L.D., E. Sourdeau, N.M., T.-A.S., D.C., L.M., A. Stoclin, C.W., F. Pommeret, F.B., A.M., and F. Pène; Data Curation, L.D., C.A., C.H., and M.F.; Validation, M.F., and E. Solary; Visualization, A. Silvin, G.D., A.-G.G., A.D., F. Ginhoux, M.F., and E. Solary; Writing – Original Draft, E. Solary; Writing – Review & Editing, A. Silvin, F. Ginhoux, M.F., and E. Solary; Supervision, F. Ginhoux, M.F., and E. Solary.
PY - 2020/9/17
Y1 - 2020/9/17
N2 - 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-DRLow 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.
AB - 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-DRLow 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.
UR - http://www.scopus.com/inward/record.url?scp=85089528043&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.08.002
DO - 10.1016/j.cell.2020.08.002
M3 - مقالة
SN - 0092-8674
VL - 182
SP - 1401
EP - 1418
JO - Cell
JF - Cell
IS - 6
ER -