Background: No previous research has investigated the direct effects of exercise interventions on COVID-19 outcomes. The aim is to investigate the effect of 8 weeks of home-based moderate-intensity continuous training (MICT), resistance training (RT), and combined aerobic and resistance training (CET) on biochemical and hematologic markers associated with COVID-19 symptoms and severity in COVID-19 survivors. Methods: A total of 547 male and female COVID-19 survivors were screened, and 296 (aged 20–93 years) were randomly assigned in a 1:1:1:1 ratio to one of four groups: MICT (n = 74), RT (n = 74), CET (n = 74), or non-exercise (NON-EX, n = 74). Blood samples were taken at baseline, at week 4, and week 8 after training. Results: After the intervention, compared with the NON-EX group, all 3 MICT, RT, and CET interventions caused significant improvements in the levels of creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive protein (CRP), troponin-I, d-dimer, creatinine, urea, potassium (K), sodium (Na), white blood cell (WBC), neutrophils, lymphocytes, red blood cells (RBC), platelets, hemoglobin, and hematocrit concentrations (P < 0.05). CET was effectively superior to MICT and RT in the improvements in the biochemical and hematological variables studied (P < 0.05). Conclusions: Overall, the present study demonstrates that long-term MICT plus RT interventions have a synergistic effect in accelerating and enhancing the recovery in patients surviving COVID-19. Trial registration IRCT20160605028270N3, 6 September 2020.

Physical exercise triggers the release of short-lived exerkines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10), which may help reduce systemic inflammation and mitigate the risk of chronic disease. Despite their potential, the effects of these exercise-induced cytokines (termed exerkines) across diverse populations remain underexplored. This study evaluated how exercise-induced exerkines modulate inflammatory markers, based on changes observed before and after intervention. We systematically searched PubMed, Scopus, and Web of Science from January 2015 up to 7 February 2025, identifying 11 randomized controlled trials (RCTs) involving 1135 participants. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model to assess changes in IL-6, TNF-α, IL-10, C-reactive protein (CRP), and interferon-gamma (IFN-γ). Study quality was evaluated using the Cochrane Risk of Bias 2 tool. Exercise significantly reduced CRP (SMD = −0.77, 95% CI: −1.20 to −0.33, p = 0.001) and TNF-α (SMD = −1.09, 95% CI: −2.14 to −0.03, p = 0.043) while increasing IL-6 (SMD = 0.81, 95% CI: 0.10 to 1.53, p = 0.026). IL-10 showed a non-significant increase (SMD = 0.66, 95% CI: −0.09 to 1.41, p = 0.084), with no effect on IFN-γ. Heterogeneity was moderate for CRP (I² = 52.5%) but high for other markers (I² > 87%). These findings suggest that exerkines contribute to an anti-inflammatory shift in the short term, which is consistent with mechanisms that may underlie the preventive effects of exercise against cardiometabolic diseases; however, standardized protocols and longitudinal studies with clinical endpoints are needed to confirm any long-term benefits.