Skip to main content
. 2021 Jun 11;22(2):112–123. doi: 10.1038/s41577-021-00558-3

Fig. 3. NK cells in COVID-19.

Fig. 3

In the circulation, natural killer (NK) cells respond strongly to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and display an altered phenotype, including elevated expression of activation markers (HLA-DR, CD69 and CD38), inhibitory molecules (TIM3, LAG3 and possibly PD1) and tissue-homing markers (CCR5, CXCR3 and CD62L). Furthermore, circulating NK cells are highly proliferative and upregulate perforin and granzyme B expression. This response is primarily confined to less differentiated NK cells, suggestive of a cytokine-driven response. NK cells likely home to the lungs, where they exhibit an inflamed transcriptional signature. In severe coronavirus disease 2019 (COVID-19), adaptive-like NK cells are found at higher frequencies in the circulation, but it remains unclear whether these cells home to the lungs and interact with infected epithelia that show increased expression of HLA-E, a ligand for the activating receptor NKG2C. Furthermore, the transcriptional profile of NK cells in the lung microenvironment of patients with severe COVID-19 is even further skewed towards inflammation. This lung microenvironment also contains high numbers of myeloid-derived suppressor cells (MDSCs) and immature neutrophils. However, details on how NK cells might interact with these cells remain elusive. Additional outstanding questions related to NK cells in COVID-19 are highlighted in the figure. CCL, CC-chemokine ligand; CCR, CC-chemokine receptor; CXCL, CXC-chemokine ligand; CXCR, CXC-chemokine receptor; KIR, killer cell immunoglobulin-like receptor; LAG3, lymphocyte activation gene 3; TIGIT, T cell immunoreceptor with immunoglobulin and ITIM domains; TIM3, T cell immunoglobulin mucin receptor 3.