OSTEOPONTINA COMO MARCADOR DE GRAVIDADE E PROGNÓSTICO EM PACIENTES COM COVID-19 E SUA RELAÇÃO COM VARIÁVEIS CLÍNICAS E EPIDEMIOLÓGICAS

Abstract

Predicting the severity and prognosis of COVID-19 through feasible biomarkers remains challenging for the scientific community. This study aims to identify in the literature evidence of the contribution of osteopontin (OPN) in the early assessment of the severity of COVID-19, its potential as a predictor of unfavorable outcomes, and to identify its correlation with other cytokines of the immune response. Two articles make up this volume: A systematic review composed of 13 articles, involving adult and pediatric participants, that investigated osteopontin as a marker of severity, prognosis, mortality, and immunopathogenesis aspects in COVID-19. The studies were carried out in Europe, Asia, and North America, and a gap in the behavior of this biomarker was evidenced in populations of developing countries. The outcomes evaluated indicate that OPN plays a role in the immunopathogenesis of COVID-19, identifies different levels of severity, and predicts poor prognosis. The OPN cut-off points for distinguishing severity and prognosis were different and difficult to compare between studies, reiterating the need for further investigations. The second article presents an evaluation of a prospective cohort, with participants ≥18 years old, with a confirmed diagnosis of COVID-19, admitted to the ICU of a Hospital in the Northeast of Brazil. The association of OPN with clinical and immunological parameters was performed using Poisson regression with robust variance. The OPN cutoff point at admission for the prognosis of death was estimated using the ROC curve. Of the 52 participants, 55.8% were male and 63.5% were 60 or older. The OPN cut-off point at admission was ≥31.0 ng/ml (AUC:0.743). High OPN at admission was associated with prognosis death (RR: 2.31, 95% CI: 1.34-3.98), severe anemia (RR: 1.67, 95% CI: 1.03-2.70), and elevated CRP ≥173.5 mg/dL (RR: 2.46, 95% CI: 1.34-4.52). The positively correlated immunological markers significantly associated with OPN at admission were IL-1β, IL-2, TGF β, and IFN-γ. Elevated osteopontin at admission emerged as a good marker of unfavorable prognosis at admission and after 5 days in the ICU. The associated immunological signatures of high OPN (≥31.0ng/ml) at admission favor hyperinflammatory responses, promote the migration and activation of macrophages and T cells, and a receptive microenvironment for pro-inflammatory and pro-fibrotic actions. Conclusion: In the population analyzed, OPN proved to be an important biomarker of unfavorable prognosis and higher mortality in COVID 19. OPN has an important relationship with inflammatory response, lasting longer as a predictor until the 5th day after ICU admission. Further studies are needed to better understand OPN with other cytokines and the longevity of this biomarker in long COVID.