Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease

Abstract

Immune response dysregulation plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. In this study, we evaluated immune and endothelial blood cell profiles of patients with coronavirus disease 2019 (COVID-19) to determine critical differences between those with mild, moderate, or severe COVID-19 using spectral flow cytometry. We examined a suite of immune phenotypes, including monocytes, T cells, NK cells, B cells, endothelial cells, and neutrophils, alongside surface and intracellular markers of activation. Our results showed progressive lymphopenia and depletion of T cell subsets (CD3+, CD4+, and CD8+) in patients with severe disease and a significant increase in the CD56+CD14+Ki67+IFN-γ+ monocyte population in patients with moderate and severe COVID-19 that has not been previously described. Enhanced circulating endothelial cells (CD45−CD31+CD34+CD146+), circulating endothelial progenitors (CD45−CD31+CD34+/−CD146−), and neutrophils (CD11b+CD66b+) were coevaluated for COVID-19 severity. Spearman correlation analysis demonstrated the synergism among age, obesity, and hypertension with upregulated CD56+ monocytes, endothelial cells, and decreased T cells that lead to severe outcomes of SARS-CoV-2 infection. Circulating monocytes and endothelial cells may represent important cellular markers for monitoring postacute sequelae and impacts of SARS-CoV-2 infection during convalescence and for their role in immune host defense in high-risk adults after vaccination.

Philadelfia-negative myeloproliferative neoplasms display alterations in monocyte subpopulations frequency and immunophenotype

“…These cells are associated with IFN-γ and granzyme B secretion and highactivated pro le; their number increase in the rst ve days of infection and they remain proliferative at the sixteenth day after the PCR test con rmation. CD56 + monocytes probably participate in the exacerbated immune response that lead to tissue and organ damage and dysfunction in COVID-19 and the frequency of these cells positively correlate with hypertension in these patients [45].…”

Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C—Can We Match the Puzzle?

“…For example, in patients with COVID-19, the number of CD14++CD16− T lymphocytes is typically low, while CD14++CD16+ (intermediate) and CD14+CD16++ (non-classical) monocytes increase [ 38 , 39 ]. Recently described CD56+CD14+Ki67+IFN-γ+ monocyte may play a crucial role in severe COVID-19 [ 40 ].…”

“…In children, novel insights showed that the typical polyclonal Vβ21.3+ T cell expansions might be associated with MIS-C [ 40 ]. The activated phenotype of Vβ21.3+ T cells express high levels of CX3CR1, a marker of patrolling monocytes and cytotoxic lymphocytes.…”

“…Moreover, the CX3CR1-CX3CL1 axis probably leads to vascular inflammation in MIS-C. Furthermore, it is possible that Vβ21.3+ CD4 and CD8 T cell expansions may be the distinctive marker of MIS-C compared to KD and COVID-19 [ 40 ].…”

Diffuse mononuclear inflammatory response to COVID-19: friendly fire or smoldering enemy?

“…However, because many of the necrotic myocytes showed evidence of contraction band necrosis, we believe that the majority injury is due to microvascular/endothelial injury and consequent ischemia/reperfusion injury. Interestingly, a recent report by Dutt et al demonstrates that enhanced circulating endothelial cells (CD452CD31+ CD34+ CD146+), circulating endothelial progenitors (CD452CD31+ CD34+/2CD1462), and neutrophils (CD11b+ CD66b+) correlated with the severity of COVID-19 disease suggesting that SARS-CoV-2 infection causes damage and increased turnover of endothelial cells [9] . In our recent review article we pointed out a possible important role of monocyte-derived macrophages in the pathogenesis of severe COVID-19 induced myocardial damage either by causing a cytokine-mediated endothelial damage and/or by causing localized endothelial damage/apoptosis [10] .…”