Natural Killer Cells in SARS-CoV-2 Infection: Pathophysiology and Therapeutic Implications

• Published in: Frontiers in immunology 2022-06, Vol.13, p.888248-888248
• Main Authors: Di Vito, Clara, Calcaterra, Francesca, Coianiz, Nicolò, Terzoli, Sara, Voza, Antonio, Mikulak, Joanna, Della Bella, Silvia, Mavilio, Domenico
• Format: Article
• Language: English
• Subjects: COVID-19; Immunology; immunotherapy; memory-like; NK cells; SARS-CoV-2 infection; single cell sequencing
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.888248

Natural Killer (NK) cells are lymphocytes of the innate immunity that play a crucial role in the control of viral infections in the absence of a prior antigen sensitization. Indeed, they display rapid effector functions against target cells with the capability of direct cell killing and antibody-dependent cell-mediated cytotoxicity. Furthermore, NK cells are endowed with immune-modulatory functions innate and adaptive immune responses via the secretion of chemokines/cytokines and by undertaking synergic crosstalks with other innate immune cells, including monocyte/macrophages, dendritic cells and neutrophils. Recently, the Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the specific role of NK cells in COVID-19 pathophysiology still need to be explored, mounting evidence indicates that NK cell tissue distribution and effector functions could be affected by SARS-CoV-2 infection and that a prompt NK cell response could determine a good clinical outcome in COVID-19 patients. In this review, we give a comprehensive overview of how SARS-CoV-2 infection interferes with NK cell antiviral effectiveness and their crosstalk with other innate immune cells. We also provide a detailed characterization of the specific NK cell subsets in relation to COVID-19 patient severity generated from publicly available single cell RNA sequencing datasets. Finally, we summarize the possible NK cell-based therapeutic approaches against SARS-CoV-2 infection and the ongoing clinical trials updated at the time of submission of this review. We will also discuss how a deep understanding of NK cell responses could open new possibilities for the treatment and prevention of SARS-CoV-2 infection.