Assessing the impact of COVID-19 on NK cells

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Severe COVID-19 induces strong alterations in the peripheral immune system. Some immune cell types take on a protective role in this disease, while others contribute to disease pathology. One cell type whose functional role in COVID-19 is not yet known is the natural killer (NK) cell. In order to better understand the NK cell response to this disease, we profiled NK cells and whole PBMC from donors across the COVID-19 severity spectrum using CyTOF, single-cell RNA sequencing, and single-cell ATAC sequencing. We found that severe COVID-19 induces strong activation of peripheral NK cells. The activated NK cells in severe COVID-19 patients also downregulate surface expression, but not transcriptional expression, of the activating receptors DNAM-1 and NKG2D. As both of these receptors can be internalized upon ligation, we assessed expression of the ligands for these receptors on other peripheral immune cells and identified a significant increase in the expression of the ligands for NKG2D and DNAM-1 on the monocytes of severe COVID-19 patients. Collectively, our results suggest that monocytes may activate NK cells via the ligation of activating receptors in severe COVID-19.