SARS-CoV-2 infection reduces the frequencies of angiogenic CD4 and CD8 T cells (T-ang)

Abstract SARS-CoV-2 is one of the leading causes of mortality worldwide with rising death toll over 5.4 million. The severe presentation of the disease is associated with systemic inflammation, activation of the coagulation cascade and immunological dysfunction. Numerous studies implicate endothelial activation and dysfunction as playing an important role; however, the pathways involved are not well-understood. Endothelial injury and damage trigger a mechanism of vascular repair mediated by bone marrow derived endothelial progenitor cells and recently discovered a type of T cells with angiogenic properties. In this study, we hypothesize that SARS-COV-2 alters this pathway. To address this hypothesis, we determined changes in the frequency and phenotype of these two cell types, the circulating endothelial progenitor (EPC) (LIN4−CD45−CD34+) and Tang cells (CXCR4+CD31+) using PBMCs from hospitalized COVID-19 positive (n = 10) and healthy (n = 11) donors. Our results indicate a decrease in the frequency of CD4 and CD8 Tang cells compared with healthy controls (p=0.003; p=0.01). In addition, Tang cells showed a significant increase in the expression of progenitor marker (CD49f) (p<0.001; p=0.016), and no changes were observed in the frequency and phenotype of the LIN4−CD45−CD34+. Moreover, a negative association was observed between Tang cells and plasma levels of the procoagulant PAI-1 biomarker (r=−0.806, p=0.007; r=−0.818, p=0.006), and CD8 Tang cells were inversely correlated with the levels of MMP9 and TNFa, (r=−0.879, p=0.002; r=−0.709, p=0.027). Altogether these data suggest that SARS-CoV-2 infection reduces the frequency of Tang cells and promote activation and may interfere with their vascular repair function.