Dysregulation of NK cell subsets and phenotypes in COVID-19 patients with comorbid type 2 diabetes.

Recent studies have linked natural killer (NK) cells to COVID-19. However, the role of NK cells in COVID-19 patients complicated with type 2 diabetes (T2D) remains unexplored. Our findings indicate no significant differences in the frequency or immunophenotype of total NK cells and the CD56bright CD16- subset among COVID-19 patients, T2D patients, and healthy individuals. Patients with severe COVID-19 had a greater prevalence of CD56dim CD16- cells subset and a lower prevalence of CD56dim CD16+ cells subset, with these trends being even more pronounced in those with comorbid T2D. The proportion of CD56dim CD16+ cell subset exhibited a significant negative correlation with both interleukin-6 levels and the duration of hospital stay. Furthermore, when COVID-19 patients were compared with patients with T2D or control subjects, a trend was noted toward increased expression of CD69, KIR, and CD52 and decreased expression of CD226, NKG2D, and CD62L. These immunophenotypic changes were particularly accentuated in COVID-19 patients with comorbid T2D. Importantly, the CD56dim CD16+ cells subset emerges as a substantial predictor of COVID-19 severity. Together, COVID-19 patients exhibit alterations in NK cell subsets, with aggravated dysregulation in individuals with T2D, and the CD56dim CD16+ cells subset may serve as an indicator of COVID-19 severity.