RESUMO
BACKGROUND: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight. RESULTS: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56+CD16-) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56+CD16+), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4+CD38+ cells than controls. Contrasting changes were reported in CD25+CD127low/neg regulatory T cells, with increased and decreased proportions found in CD4+ and CD8+ T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4+ and CD8+) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8+CD57+NKG2A+ cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19. CONCLUSIONS: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight.
RESUMO
BACKGROUND: Asthma control is not well reflected by spirometry, yet this is the most frequently used measure of lung function in asthma clinics. Oscillometry is an alternative technique suitable for those with severe asthma. OBJECTIVE: To investigate usefulness of oscillometry in subjects with severe asthma to determine which outcome variables best reflected asthma control. METHODS: Adults with severe asthma were recruited from a severe asthma clinic in Brazil. Oscillometry (conventional multifrequency measurements between 6 and 32 Hz; intrabreath tracking at 8 Hz) and spirometry were performed. Asthma control was determined by the asthma control test. RESULTS: A total of 60 adults were evaluated; mean age was 56.7 years. There was predominance of women (82%), and most patients (63%) reported onset of asthma symptoms in childhood or adolescence. There were no differences between controlled and uncontrolled asthma in spirometry. Uncontrolled asthma was associated with higher resistance (at 8 and 10 Hz) and more negative reactance (for 6, 8, and 10 Hz) (P < .05) on conventional oscillometry. Intrabreath oscillometry revealed significant differences between controlled and uncontrolled patients with asthma (P < .01 for changes in resistance and reactance between end expiration and end inspiration). The accuracy of the lung function tests in discriminating between controlled and uncontrolled asthma was higher for intrabreath variables (area under the curve = 0.65-0.72). CONCLUSION: Oscillometry, particularly the intrabreath technique, better reflected asthma control than spirometry measures. Our findings suggest that oscillometry may be a useful technique to aid management of severe asthma, with a potential to reflect loss of disease control.