| Popis: |
Unvaccinated COVID-19 patients display a large spectrum of symptoms, ranging from asymptomatic to severe symptoms, the latter even causing death. Distinct Natural killer (NK) and CD4 (+) and CD8 (+) T cells immune responses are generated in COVID-19 patients. However, the phenotype and functional characteristics of NK cells and T-cells associated with COVID-19 pathogenesis versus protection remain to be elucidated. In this study, we compared the phenotype and function of NK cells SARS-CoV-2-specific CD4 (+) and CD8 (+) T cells in unvaccinated symptomatic (SYMP) and unvaccinated asymptomatic (ASYMP) COVID-19 patients. The expression of senescent CD57 marker, CD45RA/CCR7differentiation status, exhaustion PD-1 marker, activation of HLA-DR, and CD38 markers were assessed on NK and T cells from SARS-CoV-2 positive SYMP patients, ASYMP patients, and Healthy Donors (HD) using multicolor flow cytometry. We detected significant increases in the expression levels of both exhaustion and senescence markers on NK and T cells from SYMP patients compared to ASYMP patients and HD controls. In SYMP COVID-19 patients, the T cell compartment displays several alterations involving naive, central memory, effector memory, and terminally differentiated T cells. The senescence CD57 marker was highly expressed on CD8 (+) T (EM) cells and CD8 (+) T (EMRA) cells. Moreover, we detected significant increases in the levels of proinflammatory TNF-α, IFN-γ, IL-6, IL-8, and IL-17 cytokines from SYMP COVID-19 patients, compared to ASYMP COVID-19 patients and HD controls. The findings suggest exhaustion and senescence in both NK and T cell compartment is associated with severe disease in critically ill COVID-19 patients. IMPORTANCE: Unvaccinated COVID-19 patients display a large spectrum of symptoms, ranging from asymptomatic to severe symptoms, the latter even causing death. Distinct Natural killer (NK) and CD4 (+) and CD8 (+) T cells immune responses are generated in COVID-19 patients. In this study, we detected significant increases in the expression levels of both exhaustion and senescence markers on NK and T cells from unvaccinated symptomatic (SYMP) compared to unvaccinated asymptomatic (ASYMP) COVID-19 patients. Moreover, we detected significant increases in the levels of proinflammatory TNF-α, IFN-γ, IL-6, IL-8, and IL-17 cytokines from SYMP COVID-19 patients, compared to ASYMP COVID-19 patients. The findings suggest exhaustion and senescence in both NK and T cell compartment is associated with severe disease in critically ill COVID-19 patients. TWEET: Significant exhaustion and senescence in both NK and T cells were detected in unvaccinated symptomatic COVID-19 patients, suggesting a weakness in both innate and adaptive immune systems leads to severe disease in critically ill COVID-19 patients. |
