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

Abstract

Highlights d Patients with severe COVID-19 accumulate HLA-DR Low monocytes and immature neutrophils in blood/lungs d Calprotectin level positively correlates with neutrophil count and disease severity d Loss of non-classical monocytes could identify high risk of severe COVID-19

Mass cytometry and artificial intelligence define CD169 as a specific marker of SARS-CoV2-induced acute respiratory distress syndrome

“…Interestingly, we also found an upregulation of cytoplasmic S100A9 in monocyte subsets specifically amplified in COVID-19 patients irrespectively of their ARDS status. These data suggest that, in the early stage of the disease, monocytes could contribute to the burst of circulating calprotectin (S100A8/S100A9), recently proposed to contribute to the secondary cytokine release syndrome described in severe COVID-19 and attributed to neutrophils (18).…”

“…The amplification of CD169 pos circulating monocytes has already been highlighted in the context of COVID-19 (11,18,36,37), and is reminiscent of other inflammatory conditions found in viral infections, such as with Human Immunodeficiency Virus or Epstein-Barr Virus, in which the CD169 sialoadhesin is induced in an IFN-dependent manner on the surface of circulating monocytes (38,39). Consistent with the inflammatory response, we showed that the accumulation of CD169 pos monocytes in COVID-19 pos patients is positively correlated with an increase of plasmablasts and mature plasma cells, Th1-like CD8 effector T cells, cytotoxic mature NK cells, and activated CD4 effector memory T cells displaying a CTLA4 high PD1 high phenotype.…”

“…Immune response to COVID-19 infection has been recently intensively studied at transcriptomic and proteomic levels. However, most studies focused on either the lymphoid (15,17,19) or the myeloid compartments (9,16,18), and only few performed a wide analysis of the circulating immune landscape (10,12,13,20,32), thus precluding the definition of complex patterns of immune parameter alterations associated with COVID-19 severity or physiopathology. Moreover, these works were designed to identify differences in immune cell subset frequencies between COVID-19 patients and healthy donors, and eventually correlated with the severity of the disease, but did not include severe non-COVID-19 patients as controls, although critically ill patients were largely demonstrated previously to display immune reprogramming (33).…”

“…Consistent with the inflammatory response, we showed that the accumulation of CD169 pos monocytes in COVID-19 pos patients is positively correlated with an increase of plasmablasts and mature plasma cells, Th1-like CD8 effector T cells, cytotoxic mature NK cells, and activated CD4 effector memory T cells displaying a CTLA4 high PD1 high phenotype. CD169 pos activated monocytes were detected in mild disease (18), and were proposed to rise rapidly and transiently in patients with COVID-19, in association with a high expression of IFNγ and CCL8 (11). This could be due to the transient nature of this monocytic population, either losing CD169, being short-lived, or being recruited into tissues as CD169 pos macrophages, as suggested by the high expression of CCR2 on Mo243 and Mo180, the two monocyte subsets identified here in COVID-19 patients, and the local inflammation and lung tissue destruction mediated by monocytederived macrophages in severe cases of SARS-CoV2 infections (40,41).…”

“…A number of high-resolution studies have recently concentrated on the determination of circulating markers that can distinguish severe from mild forms of COVID-19, providing a tremendous amount of data describing phenotypic and functional alterations in T cell, B cell, and myeloid cell subsets (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). In particular, CD14 pos HLA-DR low , CD14 pos CD16 pos , CD14 low CD16 pos , and immature monocytes were demonstrated as increased among peripheral blood mononuclear cells (PBMCs) from critically ill COVID-19 patients (11,16,18,(21)(22)(23). Various alterations of lymphoid cells have also been described, including a T-cell lymphopenia, predictive of patient outcome, a broad T-cell activation including Th1, Th2, and Th17, an alteration of B-cell and T-cell repertoires, and a strong increase of plasmablasts, most prominent in ARDS COVID-19 patients (12,20,(24)(25)(26).…”