Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and “brain fog”. Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia.

Cardiac resynchronization therapy (CRT) improves prognosis in patients with moderate-to-severe heart failure, reduced left ventricular ejection fraction, and wide QRS complexes. However, CRT may be under-utilized in women and data on long-term follow-up are still scarce. The aim was to investigate long-term mortality and hospitalization and prognostic impact of gender after CRT. Data on 619 consecutive patients (19% women) that received CRT at a single centre between 1998 and 2008 were collected from electronic medical records and national death and hospitalization registries up to 2010. The primary endpoint was death of any cause and the secondary endpoint was combined death of any cause or heart failure hospitalization. Over a mean follow-up of 1320 ± 786 days, 215 (35%) patients reached the primary endpoint and 437 (71%) the secondary endpoint. Overall, 1-, 5-, and 10-year survivals were 91, 63, and 39%, respectively. Female gender was the only independent predictor of all-cause mortality; hazard ratio (HR) 0.44 [95% confidence interval (CI), 0.21–0.90; P= 0.025]. Women also had a trend towards lower risk for the secondary endpoint, HR 0.68 (95% CI, 0.45–1.04; P= 0.072). In this registry analysis, patients with CRT had similarly high short-term survival to those in controlled trials, and this favourable prognosis was sustained over the long term.Women had lower all-cause mortality than men.

Objective: To compare muscle fiber type composition and muscle fiber area in patients with chronic polymyositis or dermatomyositis and healthy controls, and to determine whether physical training for 12 weeks could alter these muscle characteristics.Methods: Muscle fiber type composition and muscle fiber area were investigated by biochemical and immunohistochemistry techniques in repeated muscle biopsy samples obtained from 9 patients with chronic myositis before and after a 12‐week exercise program and in healthy controls. Muscle performance was evaluated by the Functional Index (FI) in myositis and by the Short Form 36 (SF‐36) quality of life instrument.Results: Before exercise, the proportion of type I fibers was lower (mean ± SD 32% ± 10%) and the proportion of type IIC fibers was higher (3% ± 3%) in patients compared with healthy controls. After exercise, percentage of type I fiber increased to 42% ± 13% (P < 0.05), and type IIC decreased to 1% ± 1%. An exercise‐induced 20% increase of the mean fiber area was also observed. The functional capacity measured by the FI in myositis and the physical functioning subscale of the SF‐36 increased significantly. Improved physical functioning was positively correlated with the proportion of type I fibers (r = 0.88, P < 0.01) and type II muscle fiber area (r = 0.70, P < 0.05).Conclusion: Low muscle endurance in chronic polymyositis or dermatomyositis may be related to a low proportion of oxidative, slow‐twitch type I fibers. Change in fiber type composition and increased muscle fiber area may contribute to improved muscle endurance and decreased muscle fatigue after a moderate physical training program.

Objective:Erythropoietin receptor (EPOR) expression in non-hematological tissues has been shown to be activated by locally produced and/or systemically delivered EPO. Improved oxygen homeostasis, a well-established consequence of EPOR activation, is very important for human skeletal muscle performance. In the present study we investigate whether human skeletal muscle fibers and satellite cells express EPOR and if it is activated by exercise.Design and methods: Ten healthy males performed 65 min of cycle exercise. Biopsies were obtained from the vastus lateralis muscle and femoral arterio-venous differences in EPO concentrations were estimated.Results: The EPOR protein was localized in areas corresponding to the sarcolemma and capillaries. Laser dissection identified EPOR mRNA expression in muscle fibers. Also, EPOR mRNA and protein were both detected in human skeletal muscle satellite cells. In the initial part of the exercise bout there was a release of EPO from the exercising leg to the circulation, possibly corresponding to an increased bioavailability of EPO. After exercise, EPOR mRNA and EPOR-associated JAK2 phosphorylation were increased.Conclusions: Interaction with JAK2 is required for EPOR signaling and the increase found in phosphorylation is therefore closely linked to the activation of EPOR. The receptor activation by acute exercise suggests that signaling through EPOR is involved in exercise-induced skeletal muscle adaptation, thus extending the biological role of EPO into the skeletal muscle.