The Role of Circulating Therapeutic MicroRNAs in Pulmonary and Muscular Function in Post-COVID-19 Athletes.

SARS-CoV-2 infection causes significant acute and long-term morbidity, including persistent pulmonary and muscular dysfunction in athletes. Physical exercise alters circulating microRNA (miR) profiles, and specific microRNAs have documented roles in inflammation, immune regulation, muscle metabolism, and regeneration. This study characterizes circulating microRNAs relevant to COVID-19 pathogenesis and post-viral recovery, including miR-155, miR-146a, the let-7 family, miR-21, miR-424, miR-1, miR-133, miR-499, miR-208, miR-486, and miR-22, and examines how different exercise modalities may modulate these microRNAs to support pulmonary and muscular function in post-COVID-19 athletes. miR-155 and miR-146a are highlighted as modulators of innate and adaptive inflammatory signaling and as mediators of cytokine responses implicated in severe COVID-19. Moreover, several microRNAs, such as miR-21, miR-155, miR-146a, and the let-7 family, converge on NF-κB and related pathways, linking altered miR expression to immune dysregulation and cytokine-driven tissue injury. Additionally, muscle-enriched and metabolism-associated microRNAs regulate myogenesis, mitochondrial biogenesis, and key metabolic pathways (PGC-1α, AMPK, mTOR)-processes essential for muscle repair, endurance recovery, and respiratory muscle support after SARS-CoV-2 infection. Different types of exercise produce distinct miR signatures; notably, moderate-intensity exercise consistently promotes anti-inflammatory and pro-repair miR patterns. We emphasize the therapeutic potential of moderate-intensity exercise as a non-pharmacological strategy to regulate miR expression, reduce cytokine-mediated damage, and support functional recovery in post-COVID-19 athletes. To our knowledge, this is the first study to link exercise-driven miR changes with functional pulmonary and muscular recovery in athletic populations recovering from COVID-19, supporting moderate-intensity exercise as a promising strategy for rehabilitation and performance restoration.