Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery.

Introduction: We have acquired significant knowledge regarding the pathogenesis of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). However, the underlying mechanisms responsible for disease recovery still need to be fully understood. Methods: To gain insights into critical immune markers involved in COVID-19 etiopathogenesis, we studied the evolution of the immune profile of peripheral blood samples from patients who had recovered from COVID-19 and compared them to subjects with severe acute respiratory illness but negative for SARS-CoV-2 detection (controls). In addition, linear and clustered correlations between different parameters were determined. Results: The data obtained revealed a significant reduction in the frequency of inflammatory monocytes (CD14+CD16+) at hospital discharge vs. admission. Remarkably, nitric oxide (NO) production by the monocyte compartment was significantly reduced at discharge. Furthermore, interleukin (IL)-6 plasma levels were negatively correlated with the frequency of NO+CD14+CD16+ monocytes at hospital admission. However, at the time of hospital release, circulating IL-6 directly correlated with the NO production rate by monocytes. In line with these observations, we found that concomitant with NO diminution, the level of nitrotyrosine (NT) on CD8 T-cells significantly diminished at the time of hospital release. Considering that purinergic signaling constitutes another regulatory system, we analyzed the kinetics of CD39 and CD73 ectoenzyme expression in CD8 T-cells. We found that the frequency of CD39+CD8+ T-cells significantly diminished while the percentage of CD73+ cells increased at hospital discharge. In vitro, IL-6 stimulation of PBMCs from COVID-19 patients diminished the NT levels on CD8 T-cells. A clear differential expression pattern of CD39 and CD73 was observed in the NT+ vs. NT-CD8+ T-cell populations. Discussion: The results suggest that early after infection, IL-6 controls the production of NO, which regulates the levels of NT on CD8 T-cells modifying their effector functions. Intriguingly, in this cytotoxic cell population, the expression of purinergic ectoenzymes is tightly associated with the presence of nitrated surface molecules. Overall, the data obtained contribute to a better understanding of pathogenic mechanisms associated with COVID-19 outcomes.

Associations between objectively measured physical activity, sedentary time, and cardiorespiratory fitness with inflammatory and oxidative stress markers and heart rate variability.

Background: To assess the associations between physical activity (PA) and sedentary time (SEDT) with inflammatory and oxidative stress markers, heart rate variability (HRV) and post-exercise recovery (HRR) controlling for cardiorespiratory fitness (CRF) and potential confounders. Design and methods: The following data was collected from 44 participants during 2019 (age = 49.5 ± 6.4 years, 66% women): Plasma levels of C-reactive protein (CRP) and cytokines (IL-1ß, INF-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-18, IL-23); catalase (CAT) and glutathione peroxidase (GPX) activities; resting heart (HR) rate for HRV analysis, anthropometric measures, a submaximal cycling test to evaluate CRF with active recovery to assess and HRR (absolute and ΔHR), and 7-day accelerometry. Results: Women spent significantly more SEDT (p = 0.035), had higher inflammatory markers (IL-6 and TNF) and lower HRV indices [SDNN, LF/HF, SD2 (p > 0.05)]. Significant associations were found between SEDT and markers of inflammation [CRP, B = 0.006, p = 0.001; MCP-1, B = 0.003, p = 0.038]. HRV indices were significantly associated with inflammatory/oxidative stress markers [IL-10 (p = 0.04), GPX (p = 0.014), ln-IL 23 (p = 0.036), CAT (p = 0.026)] while HRR was positively associated with light PA [Δ3 (B = 0.051, p = 0.043), Δ4 (B = 0.062, p = 0.021)] and inversely related to catalase [Δ3 (B = -54.7, p = 0.042), Δ4 (B = -54.1, p = 0.021] and CRP [Δ5 (B = -19.8, p = 0.033)]. Higher CRF showed lower values for TNF-α (p = 0.02) and IL-10 (p = 0.003) and better HRV/HRR indices [RMSSD, PNS, SampEn, SD1 (p < 0.05)]. Conclusions: SEDT had a higher impact on inflammation and autonomic balance, independently of PA levels with differences by sex and CRF. PA appears to be more important for a better HRR. Lower HRV and HRR could be indicative of inflammatory status.