Análise epidemiológica e imunológica de pacientes com obesidade hospitalizados com síndrome respiratória aguda grave causada por COVID-19 no Brasil

Abstract

During the COVID-19 pandemic, it was observed that obesity influences the prognosis of this disease. However, its relationship with the clinical outcomes of COVID-19 needs to be investigated in the Brazilian population, as well as the characteristics of the immunological response that this population with obesity may present in a severe condition. Thus, the goal was to investigate the influence of obesity in cases of severe acute respiratory syndrome (SARS) by COVID-19 in Brazil, its association with severity and mortality, and the immune response of critically ill patients. This thesis resulted in two studies, both with data from 2020. Study 1 is an ecological study developed from the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe), with data from adults and elderly people hospitalized with SARS due to COVID-19 with a known clinical outcome. Descriptive and comparative data analysis was performed to investigate the differences between patients with (OB) and without (N-OB) obesity. Then, a spatial analysis was performed between Brazilian regions. Finally, logistic regression was applied to the total population and, later, only to the obese population. Study 2 involved a cross-sectional analysis with the inclusion of 27 severe COVID-19 patients (67% women, 56.33 ± 19.55 years), assigned to OB group (BMI ≥ 30 kg/m², n = 9) or N -OB (BMI < 30 kg/ m², n = 18). Immune cells (monocytes, neutrophils, NK cells and T lymphocytes) were isolated from peripheral blood and the frequency and expression of surface receptors were analyzed by flow cytometry. In both phases, the assumed significance level was 5%. In study 1, obesity was the third most frequent among hospitalizations (8.5%), however, it had a significantly higher odds ratio (OR) for invasive ventilatory support (OR: 2.48; 95%CI: 2. 37 – 2.60), non-invasive (OR: 1.59; 95%CI: 1.53 – 1.65), ICU admission (OR: 1.74; 95%CI: 1.69 – 1.79) and mortality (OR: 1.36; 95%CI: 1.32 – 1.40), compared to the most prevalent diseases. OB patients were younger than N-OB (p < 0.001). The mixed-race and black ethnic groups, the North and Northeast regions and illiterates were more affected in mortality rates. Chronic kidney disease was the only comorbidity associated with mortality in the OB population. OB patients on invasive ventilatory support had a seven times greater chance of mortality. In study 2, a negative association was observed between the frequency of monocytes and lymphocytes and BMI, while NK and neutrophils were positively associated (p < 0.05). OB patients had monocytes with high expression of PD-L1 (p < 0.05) and a significant reduction in CD3+ lymphocytes, specifically cytotoxic, as well as a higher frequency of the CD4+CD28+CD279+ phenotype (p < 0.05). In these patients, a higher frequency of NK cells and TREM-1+ expression on neutrophils was observed (p < 0.05). Finally, expression of receptors related to antigen presentation, phagocytosis, chemotaxis, inflammation, and suppression were strongly associated with clinical markers only in OB patients (p < 0.05). These data support that obesity influenced to the severity and mortality of COVID-19 in Brazil and it differentially affects the immune response in severe cases.