Avaliação da influência de fatores transgênicos, transcricionais e séricos relacionados às células natural killer desfecho clínico e a gravidade em pacientes com Covid-19

Abstract

Introduction: COVID-19 is a highly transmissible respiratory disease that, although it has become less severe in most parts of the world, continues to pose a significant challenge to public health. This is due to the fact that it still results in thousands of deaths and raises concerns because of the emergence of new variants, in addition to gaps in knowledge regarding the complex interaction between the virus and the host. Natural killer (NK) cells play a crucial role in host defense against viruses. Despite reports of decreased NK cell counts in COVID-19 patients, particularly in severe cases, the contribution of their cytotoxic proteins to the pathogenesis of the disease remains unclear. Objective: This cohort study aimed to evaluate the role of genes related to the activation, development, and effector mechanisms of NK cells, as well as the potential immunomodulatory role of viral infection. Methods: The study included 140 COVID-19 patients from hospitals in Uberaba, MG, Brazil, in 2020 and 2021. The analysis involved assessing the presence of the A91V polymorphism in the perforin gene, the Q48R polymorphism in the granzyme B gene, and quantifying the gene expression of PRF1, GZMB, TBX21, EOMES, IL15, RUNX3, and IFNG. The association of these data with clinical outcomes and disease severity was evaluated. Additionally, a functional assay was performed on peripheral blood mononuclear cells (PBMCs) stimulated with plasma from infected patients, quantifying the cytotoxic proteins perforin and granzyme B, and the cytokines IL-17A, IFN-γ, TNF, IL-10, IL-6, IL-4, and IL-2, as well as gene expression under stimulation. Results and discussion: The presence of the analyzed polymorphisms did not differ between severity parameters and outcomes. Furthermore, patients who were discharged had higher expression of perforin, granzyme B, Eomes, and IL-15 genes compared to those who died. The same was observed in patients with less severe disease, for perforin, granzyme B, and IL-15, indicating greater lymphocyte activation and consequently higher expression of these genes, leading to a better prognosis. Additionally, cells incubated with plasma from infected individuals showed lower expression of cytotoxic proteins and higher expression of pro-inflammatory cytokines. Considering these aspects, the present research provides a better understanding of the virus-host relationship, which may be useful in more appropriate patient management, identifying those at higher risk, as well as in the development or identification of more effective drugs.