Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.

Role of Body Mass and Physical Activity in Autonomic Function Modulation on Post-COVID-19 Condition: An Observational Subanalysis of Fit-COVID Study.

The harmful effects of coronavirus disease 2019 (COVID-19) can reach the autonomic nervous system (ANS) and endothelial function. Therefore, the detrimental multiorgan effects of COVID-19 could be induced by deregulations in ANS that may persist after the acute SARS-CoV-2 infection. Additionally, investigating the differences in ANS response in overweight/obese, and physically inactive participants who had COVID-19 compared to those who did not have the disease is necessary. The aim of the study was to analyze the autonomic function of young adults after mild-to-moderate infection with SARS-CoV-2 and to assess whether body mass index (BMI) and levels of physical activity modulates autonomic function in participants with and without COVID-19. Patients previously infected with SARS-CoV-2 and healthy controls were recruited for this cross-sectional observational study. A general anamnesis was taken, and BMI and physical activity levels were assessed. The ANS was evaluated through heart rate variability. A total of 57 subjects were evaluated. Sympathetic nervous system activity in the post-COVID-19 group was increased (stress index; p = 0.0273). They also presented lower values of parasympathetic activity (p < 0.05). Overweight/obese subjects in the post-COVID-19 group presented significantly lower parasympathetic activity and reduced global variability compared to non-obese in control group (p < 0.05). Physically inactive subjects in the post-COVID-19 group presented significantly higher sympathetic activity than active subjects in the control group. Parasympathetic activity was significantly increased in physically active subjects in the control group compared to the physically inactive post-COVID-19 group (p < 0.05). COVID-19 promotes changes in the ANS of young adults, and these changes are modulated by overweight/obesity and physical activity levels.