Exercise And Lymphocyte Activation Responses In Patients With Post-covid-19 Syndrome: An Exploratory Analysis From “Exer-covid” Trial

OBJECTIVES: Regular exercise is associated with changes in peripheral blood mononuclear cell (PBMC) proportions that have enhanced effector functions in humans; however, the effects of physical exercise on PBMCs in patients with long COVID-19 are unknown. To fill this gap, the activation status of isolated PBMCs was characterized before and after muscle power resistance training (PRT) followed by 6 weeks of usual care (n = 20) or 6 weeks of usual care followed by 6 weeks of muscle PRT (n = 20). METHODS: The crossover study included 40 patients with post-COVID-19 conditions at a single center in Spain from March 1, 2021, to September 30, 2022. PBMCs were isolated by FICOL gradients. Immune cell subpopulations were quantified using FlowJo. The percentages of the different immune subpopulations were studied prior to the initiation of and after each period of intervention. RESULTS: The intervention significantly improved the peak V̇O2 by 5.73 mL/kg/min [95% CI 8.04 to 3.42], P < 0.001. After power PRT, strength (1RM) was improved for bilateral leg-press and knee extension (P < 0.001). Significant decreases were found in psychological distress scores (P < 0.001). Regarding immunity, despite the modest number of patients and the relatively short period (6 weeks) of exercise, specific changes in the proportions of several immune cell subpopulations were observed in the patients who practiced PRT. Particularly, an increase in memory/memory effector CD4 T cells, as well as a decrease in the proportion of PD-1+ CD8+ naive T cells, were observed after 6 weeks of physical exercise. PD-1 is usually described as a marker of exhaustion, although it is also known as a marker of activation. A trend toward decreased levels of exhausted effector CD4 T cells and senescent effector CD8+ T cells was also detected, supporting this hypothesis, although statistical significance was not reached. CONCLUSIONS: A supervised 6-week PRT intervention program safely improved fitness in participants with post-COVID-19 conditions. When evaluating the evolution of the immune cell subpopulations taking into account the cross-design of the trial, we observed that the changes in the proportion of these cells induced by PRT did not persist after the control period, suggesting that continuous activity was needed to achieve long-term modification of immunity.