Background: Following acute COVID-19, a substantial proportion of patients showed symptoms and sequelae for several months, namely the post-acute sequelae of COVID-19 (PASC) syndrome. Major phenomena are exercise intolerance, muscle weakness and fatigue. We aimed to investigate the physiopathology of exercise intolerance in patients with PASC syndrome by structural and functional analyses of skeletal muscle.Methods: At least 3 months after infection, non-hospitalized patients with PASC (n=11,ys:54±11; PASC) and patients without long-term symptoms (n=12,ys:49±9; CTRL) visited the laboratory on four non-consecutive days. Spirometry, lung diffusion capacity and quality of life were assessed at rest. Cardiopulmonary incremental exercise test was performed. Oxygen consumption (VO2) kinetics were determined by moderate-intensity exercises. Muscle oxidative capacity (k) was assessed by near-infrared spectroscopy. Histochemical analysis, O2 flux (JO2) by high-resolution respirometry, and quantification of key molecular markers of mitochondrial biogenesis and dynamics were performed in vastus lateralis biopsies.Results: Pulmonary and cardiac functions were within normal range in all patients. VO2peak was lower in PASC than CTRL (24.7±5.0vs32.9±7.4mL*min-1*kg-1, respectively, P<.05). VO2 kinetics was slower in PASC than CTRL (41±12vs30±9s-1, P<.05). k was lower in PASC than CTRL (1.54±0.49vs2.07±0.51min-1, P<.05). Citrate synthase, PGC1alfa and JO2 for mitochondrial complex II were significantly lower in PASC vs CTRL (all P<.05).Conclusion: In our cohort of patients with PASC, we showed limited exercise tolerance mainly due to "peripheral" determinants. Substantial reductions were observed for biomarkers of mitochondrial function, content, and biogenesis. PASC syndrome appears to negatively impact skeletal muscle function, although the disease is an heterogenous condition.

Structural and functional impairments of skeletal muscle in patients with post-acute sequelae of {SARS}-{CoV}-2 infection / M. Colosio, L. Brocca, M.F. Gatti, M. Neri, E. Crea, F. Cadile, M. Canepari, M.A. Pellegrino, B. Polla, S. Porcelli, R. Bottinelli. - In: JOURNAL OF APPLIED PHYSIOLOGY. - ISSN 8750-7587. - 135:4(2023), pp. 902-917. [10.1152/japplphysiol.00158.2023]

Structural and functional impairments of skeletal muscle in patients with post-acute sequelae of {SARS}-{CoV}-2 infection

M. Colosio
Primo
;
2023

Abstract

Background: Following acute COVID-19, a substantial proportion of patients showed symptoms and sequelae for several months, namely the post-acute sequelae of COVID-19 (PASC) syndrome. Major phenomena are exercise intolerance, muscle weakness and fatigue. We aimed to investigate the physiopathology of exercise intolerance in patients with PASC syndrome by structural and functional analyses of skeletal muscle.Methods: At least 3 months after infection, non-hospitalized patients with PASC (n=11,ys:54±11; PASC) and patients without long-term symptoms (n=12,ys:49±9; CTRL) visited the laboratory on four non-consecutive days. Spirometry, lung diffusion capacity and quality of life were assessed at rest. Cardiopulmonary incremental exercise test was performed. Oxygen consumption (VO2) kinetics were determined by moderate-intensity exercises. Muscle oxidative capacity (k) was assessed by near-infrared spectroscopy. Histochemical analysis, O2 flux (JO2) by high-resolution respirometry, and quantification of key molecular markers of mitochondrial biogenesis and dynamics were performed in vastus lateralis biopsies.Results: Pulmonary and cardiac functions were within normal range in all patients. VO2peak was lower in PASC than CTRL (24.7±5.0vs32.9±7.4mL*min-1*kg-1, respectively, P<.05). VO2 kinetics was slower in PASC than CTRL (41±12vs30±9s-1, P<.05). k was lower in PASC than CTRL (1.54±0.49vs2.07±0.51min-1, P<.05). Citrate synthase, PGC1alfa and JO2 for mitochondrial complex II were significantly lower in PASC vs CTRL (all P<.05).Conclusion: In our cohort of patients with PASC, we showed limited exercise tolerance mainly due to "peripheral" determinants. Substantial reductions were observed for biomarkers of mitochondrial function, content, and biogenesis. PASC syndrome appears to negatively impact skeletal muscle function, although the disease is an heterogenous condition.
long COVID; mitochondria; muscle oxidative metabolism; muscle weakness; myopathy
Settore BIO/09 - Fisiologia
2023
7-set-2023
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1013108
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