tetano
Editor, Senior Moderator
Exp Physiol
. 2025 Jul 20.
doi: 10.1113/EP092850. Online ahead of print. Persistence of fatigue in the absence of pathophysiological mechanisms in some patients more than 2 years after the original SARS-CoV-2 infection
Giovanni Baldassarre[SUP] 1 [/SUP], Lucrezia Zuccarelli[SUP] 1 [/SUP], Thomas Favaretto[SUP] 1 [/SUP], Caterina Ursella[SUP] 1 [/SUP], Andrea Palomba[SUP] 1 [/SUP], Paulo Cesar do Nascimento Salvador[SUP] 1 [/SUP], Emanuela Sozio[SUP] 2 [/SUP], Ernesto Crisafulli[SUP] 3 [/SUP], Massimo Imazio[SUP] 1 4 [/SUP], Carlo Tascini[SUP] 1 2 [/SUP], Bruno Grassi[SUP] 1 [/SUP]
Affiliations
Following an acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a substantial percentage of patients report the persistence of debilitating symptoms, often grouped in a syndrome termed 'long COVID'. We sought to identify potential pathophysiological mechanisms responsible for the persistence, in some long COVID patients, of symptoms related to fatigue/exercise intolerance (excessive or early fatigue, excessive or early dyspnoea, muscle weakness, and myalgias) more than 2 years after the original infection. Twelve patients who reported persistent symptoms (Long COVID group; 57 ± 6 years, mean ± SD), and 14 patients without the symptoms (Control group; 57 ± 8 years) were evaluated. An extensive series of measurements were performed to identify pathophysiological mechanisms potentially responsible for the symptoms. In long COVID patients, all items evaluating quality of life (SF-36 questionnaire) had lower scores (P < 0.01) compared to control. The habitual level of physical activity, muscle size and strength, maximal aerobic power and the ventilatory thresholds, peak cardiac function, the mechanical efficiency of cycling, pulmonary ˙VO2
kinetics, microvascular/endothelial function (hyperemic response in the common femoral artery during passive leg movements), skeletal muscle oxidative metabolism (peak fractional O[SUB]2[/SUB] extraction and muscle ˙VO2 recovery kinetics by the repeated occlusions test, by near-infrared spectroscopy) were not different in the two groups. Evidence of ventilatory inefficiency was described in a subgroup of long COVID patients. More than 2 years after the original SARS-CoV-2 infection, a discrepancy was observed between the persistence of debilitating symptoms of fatigue/exercise intolerance and the absence of several investigated pathophysiological mechanisms. The discrepancy may be due to factors that remain to be elucidated.
Keywords: exercise intolerance; exercise ventilatory inefficiency; long COVID; oxidative metabolism.
. 2025 Jul 20.
doi: 10.1113/EP092850. Online ahead of print. Persistence of fatigue in the absence of pathophysiological mechanisms in some patients more than 2 years after the original SARS-CoV-2 infection
Giovanni Baldassarre[SUP] 1 [/SUP], Lucrezia Zuccarelli[SUP] 1 [/SUP], Thomas Favaretto[SUP] 1 [/SUP], Caterina Ursella[SUP] 1 [/SUP], Andrea Palomba[SUP] 1 [/SUP], Paulo Cesar do Nascimento Salvador[SUP] 1 [/SUP], Emanuela Sozio[SUP] 2 [/SUP], Ernesto Crisafulli[SUP] 3 [/SUP], Massimo Imazio[SUP] 1 4 [/SUP], Carlo Tascini[SUP] 1 2 [/SUP], Bruno Grassi[SUP] 1 [/SUP]
Affiliations
- PMID: 40684361
- DOI: 10.1113/EP092850
Following an acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a substantial percentage of patients report the persistence of debilitating symptoms, often grouped in a syndrome termed 'long COVID'. We sought to identify potential pathophysiological mechanisms responsible for the persistence, in some long COVID patients, of symptoms related to fatigue/exercise intolerance (excessive or early fatigue, excessive or early dyspnoea, muscle weakness, and myalgias) more than 2 years after the original infection. Twelve patients who reported persistent symptoms (Long COVID group; 57 ± 6 years, mean ± SD), and 14 patients without the symptoms (Control group; 57 ± 8 years) were evaluated. An extensive series of measurements were performed to identify pathophysiological mechanisms potentially responsible for the symptoms. In long COVID patients, all items evaluating quality of life (SF-36 questionnaire) had lower scores (P < 0.01) compared to control. The habitual level of physical activity, muscle size and strength, maximal aerobic power and the ventilatory thresholds, peak cardiac function, the mechanical efficiency of cycling, pulmonary ˙VO2
kinetics, microvascular/endothelial function (hyperemic response in the common femoral artery during passive leg movements), skeletal muscle oxidative metabolism (peak fractional O[SUB]2[/SUB] extraction and muscle ˙VO2 recovery kinetics by the repeated occlusions test, by near-infrared spectroscopy) were not different in the two groups. Evidence of ventilatory inefficiency was described in a subgroup of long COVID patients. More than 2 years after the original SARS-CoV-2 infection, a discrepancy was observed between the persistence of debilitating symptoms of fatigue/exercise intolerance and the absence of several investigated pathophysiological mechanisms. The discrepancy may be due to factors that remain to be elucidated.
Keywords: exercise intolerance; exercise ventilatory inefficiency; long COVID; oxidative metabolism.