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

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-y(+) 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.

Automated summary

Immune response dysregulation plays a key role in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study evaluated immune and endothelial blood cell profiles of COVID-19 patients, revealing depletion of T cell subsets and an increase in CD56(+) monocytes in severe cases. Age, obesity, and hypertension were found to synergistically impact immune markers and disease severity in SARS-CoV-2 infection.