Adoptive transfer of natural killer cells in therapeutic treatment of COVID-19 patients

Abstract Background Natural killer (NK) cells are crucial constituents of innate immunity, playing a vital role in the early defense against viral infections and cancer. Their antiviral capabilities stem from direct cytotoxic activity against infected cells and immunoregulatory functions that modulate adaptive immune responses. In the context of Coronavirus disease (COVID-19), NK cells contribute to controlling viral replication and limiting excessive inflammatory responses. Aims This review highlights the mechanisms underlying NK cell-mediated antiviral activity, focusing on their interactions with severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). We discuss potential sources of NK cells for adoptive transfer therapy, critical factors influencing their therapeutic efficacy, and considerations for clinical translation in COVID-19 treatment. Methods Various NK cell sources for adoptive therapy are discussed, including peripheral blood, cord blood, and genetically engineered NK cells. Key factors influencing the therapeutic efficacy and safety of NK cell-based therapies are analyzed, including cytokine modulation, NK cell subset selection, and delivery methods. Conclusion Understanding the mechanisms underlying NK cell-mediated antiviral activity and the factors that influence the success of adoptive NK cell therapy can inform the design of more effective immunotherapies for COVID-19 patients. Strategies for improving NK cell function, such as genetic modification and optimizing therapy protocols, are highlighted to enhance therapeutic outcomes. Graphical Abstract NK cells neutralize SARS-CoV-2 by releasing cytotoxic granules, inhibiting replication, and modulating inflammation. They originate from peripheral blood, cord blood, and genetic engineering. Therapeutic strategies include adoptive transfer, cytokine modulation, and optimized delivery. Inflammation is controlled, reducing excessive immune responses.