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SARS CoV-2 has caused a global pandemic leading to significant morbidity and mortality. There is a need to elucidate and further understand the implications of COVID-19 disease on the immune system to develop improved therapeutic strategies. In particular, Natural Killer (NK) cells play an essential role in mediating the innate immune response against viral infections. To better understand the role of innate immunity in COVID-19, we characterized the phenotype of circulating NK cells from 74 COVID-19 patients and 25 controls. Through evaluating the protein expression of activating and inhibitory NK cell surface molecules using dimension reduction analysis and clustering, we identified 4 specific clusters of NK cells specific to disease state (COVID-19 positive or COVID-19 negative) and characterized COVID-19 positive NK cells as: NGK2A+KIR2DL1+NKG2C-. Utilizing blocking antibodies specific for receptors NKG2A and KIR2DL1, we found that both NKG2A and KIR2DL1 blockade markedly enhances the ability of NK cells from COVID-19 positive patients to lyse SARS-Cov-2 infected cells. Overall, this study reveals new insights into NK cell phenotypes during SARS-CoV-2 infection and suggests a therapeutic approach worthy of further investigation to enhance NK cell-mediated responses against the virus. [ABSTRACT FROM AUTHOR]

Keywords: chronic lymphocytic leukemia; clonal haematopoiesis; composite lymphoma; mantle cell lymphoma EN chronic lymphocytic leukemia clonal haematopoiesis composite lymphoma mantle cell lymphoma 660 664 5 02/21/23 20230301 NES 230301 Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia in the Western world, accounting for 25% of adult leukaemias. To further determine which lymphoma population displaying these cytogenetic changes, we sort-purified CLL cells and MCL cells from peripheral blood by flow cytometry (Figure 2A) and performed FISH using relevant probes. Previous studies have demonstrated that CLL and MCL in composite lymphoma cases are clonally unrelated.[[3]] For example, in the largest CLL/MCL case series, using micro-dissected tissues, Hoeller et al.[3] reported that all their seven cases of composite CLL/MCL lymphomas lacked a clonal relatedness. In addition to our findings, somatic mutations that are frequently observed in clonal haematopoiesis have also been detected in CLL and angioimmunoblastic T-cell lymphoma.[[12], [15]] However, it is unclear how these pro-myeloid mutations contribute to lymphomagenesis and at which developmental stage the mutated precursor cells transform to lymphoma initiating cells. [Extracted from the article]