Avaliação da expressão dos genes SELPLG, ITGA4, ARG1, NOS2 em leucócitos totais e níveis plasmáticos das proteínas p-selectina e PSGL-1 em pacientes com COVID-19 e sua correlação com gravidade

Abstract

INTRODUCTION: COVID-19, a disease caused by the SARS-COV-2 virus, can progress to severe cases and promote Acute Respiratory Distress Syndrome (ARDS). The pathophysiology of severe COVID is not well understood, but it appears to be related to endothelial dysfunction combined with a dysregulated immune response and cytokine storm. COVID-19 evolves quickly into severe cases, so it is of great importance to evaluate laboratory tests and biomarkers that are indicators of the host's immune response that are effective in predicting the evolution of severe cases, with the aim of optimizing clinical and therapeutic management to avoid adverse outcomes. unfavorable events, such as death. OBJECTIVE: To evaluate the expression of the ARG1, NOS2, ITGA4 and SELPLG genes in total leukocytes and measure the levels of P-selectin and PSGL-1 proteins in the plasma of patients with COVID-19, associating it with the severity of the clinical picture and the prognosis of the disease. METHODOLOGY: In this controlled observational study approved by CONEP (Opinion No.: 4,014,165) 117 patients with confirmed diagnosis of COVID-19 disease (severe = 58 and mild = 59) were recruited. Demographic, clinical, and laboratory parameters were collected at study admission. We used the RT-qPCR assay to measure the relative expression of genes. We evaluated plasmatic levels of P-selectin and PSGL-1 with ELISA assay. RESULTS: we found that men, blacks, elderly people with pre-existing comorbidities (p<0.0001) were more likely to have severe outcomes. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) (p<0.0001) were altered in the severe group. Patients with severe symptoms exhibit increased expression of the ARG1 (p=0.032) and SELPLG (p<0.0001) genes, as well as higher plasma concentrations of P-selectin (p=0.031) and PSGL-1 (p<0.002) proteins. Multivariate analysis demonstrated that hematological parameters NLR, PLR, as well as SELPLG gene expression and sPSGL-1 proteins were independent predictors of COVID-19 severity. CONCLUSION: The present study suggests that the biomarkers of endothelial dysfunction (P-selectin) and dysregulated leukocyte responses (ARG1; SELPLG and sPSGL-1) are associated with the severity of COVID-19, serving as promising predictive tools for clinical management and outcome. patient monitoring.