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• Female patients with long COVID exhibit lower cardiorespiratory fitness (CRF) than male patients. • Older age and higher body mass index are associated with lower CRF and health-related quality of life (HRQoL) in adults with long COVID. • Greater vigorous-intensity physical activity is associated with better CRF in adults with long COVID. • Greater total physical activity is associated with better CRF and sleep quality in adults with long COVID. • Greater moderate-intensity physical activity is associated with better HRQoL in adults with long COVID. To investigate the association between physical activity (PA) amount and gender differences on cardiorespiratory fitness (CRF), sleep quality, and health-related quality of life (HRQoL) in individuals with long COVID. Cross-sectional study. An integrated outpatient clinic for post-COVID-19 at a medical center. Convenience sample of patients (N=264) diagnosed with long COVID. Not applicable. PA amounts, sleep quality, and HRQoL were measured by the International Physical Activity Questionnaire, Pittsburgh Sleep Quality Index, and the World Health Organization Questionnaire on Quality of Life: Short Form, respectively. CRF was evaluated through graded exercise testing. The participants had a mean age of 42.5±13.5 years and a mean duration of post-COVID-19 symptoms of 12.7±6.8 weeks. More than half (n=149, 56.5%) were female patients. Female participants had significantly lower CRF than male participants (P <.05). Older age and higher body mass index were associated with worse CRF and HRQoL (P <.05). Less sitting behavior and greater amounts of vigorous-intensity PA (VPA) or total PA were associated with better CRF (P <.05). In addition, greater total PA and moderate-intensity PA (MPA) were associated with better sleep quality and HRQoL (P <.05), respectively. Gender differences were found in CRF among patients with long COVID. Greater self-reported VPA or total PA was associated with better CRF, whereas greater total PA and MPA were associated with better sleep quality and HRQoL, respectively, in patients with long COVID. Further research is needed to explore these associations in longitudinal studies. [ABSTRACT FROM AUTHOR]

• Telerehabilitation can increase exercise frequency and intensity in long COVID. • Telerehabilitation can enhance self-efficacy in long COVID. • Telerehabilitation can improve sleep quality in long COVID. • Telerehabilitation promotes a healthier lifestyle and improves health outcomes. Telerehabilitation has been developed and applied for years for cardiac and pulmonary diseases with good clinical outcomes. However, its application to participants with long COVID remains limited. To investigate the effectiveness of a 12-week telerehabilitation training program in participants with long COVID. The primary outcome was cardiorespiratory fitness (CRF), and secondary outcomes were physical activity (PA) amounts, exercise self-efficacy, sleep quality, and health-related quality of life (HRQOL). A parallel-group, randomized controlled trial was conducted. Eligible participants with long COVID (n = 182) were randomly assigned in a 1:1 ratio to either the experimental group (EG) or the control group (CG). The EG received 12 weeks of telerehabilitation training with weekly remote monitoring for exercise maintenance and support. The CG received PA counseling only. CRF, PA amounts, exercise self-efficacy, sleep quality, and HRQOL were assessed at baseline and 12 weeks. Generalized estimating equations were used to analyze the intervention effects by examining the interaction between time and group. One hundred twenty-two participants (67 %) completed the study, and 182 were included in the intention-to-treat analysis. The EG had greater walking behavior (β = –763.3, p < 0.001), total amount of PA (β= –711, p = 0.003), exercise self-efficacy (β = –1.19, p < 0.001), and better sleep quality (β = 1.69, p = 0.012) after the 12-weeks of telerehabilitation training than the CG. However, there were no significant differences in any CRF parameters or HRQOL at 12 weeks between the EG and CG. Telerehabilitation training offers a personalized and convenient approach that can increase exercise willingness and PA amounts and improve sleep quality. These findings underscore the potential benefits of telerehabilitation training for promoting healthier lifestyles and improving overall health outcomes. The study was registered at ClinicalTrials.gov (NCT05205460) on January 25, 2022. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of immunotherapy is limited in the majority of colorectal cancer patients due to the low mutational and neoantigen burdens in this immunogenically "cold" microsatellite stability-colorectal cancer (MSS-CRC) cohort. Here, we showed that DNA methyltransferase (DNMT) inhibition upregulated neoantigen-bearing gene expression in MSS-CRC, resulting in increased neoantigen presentation by MHC class I in tumor cells and leading to increased neoantigen-specific T-cell activation in combination with radiotherapy. The cytotoxicity of neoantigen-reactive T cells (NRTs) to DNMTi-treated cancer cells was highly cytotoxic, and these cells secreted high IFNγ levels targeting MSS-CRC cells after ex vivo expansion of NRTs with DNMTi-treated tumor antigens. Moreover, the therapeutic efficacy of NRTs further increased when NRTs were combined with radiotherapy in vivo. Administration of DNMTi-augmented NRTs and radiotherapy achieved an ∼50 % complete response and extended survival time in an immunocompetent MSS-CRC animal model. Moreover, remarkably, splenocytes from these mice exhibited neoantigen-specific T-cell responses, indicating that radiotherapy in combination with DNMTi-augmented NRTs prolonged and increased neoantigen-specific T-cell toxicity in MSS-CRC patients. In addition, these DNMTi-augmented NRTs markedly increase the therapeutic efficacy of cancer vaccines and immune checkpoint inhibitors (ICIs). These data suggest that a combination of radiotherapy and epi-immunotherapeutic agents improves the function of ex vivo- expanded neoantigen-reactive T cells and increases the tumor-specific cytotoxic effector population to enhance therapeutic efficacy in MSS-CRC. [Display omitted] • Demethylation agents upregulate neoantigen-bearing genes to increase cancer immunogenicity for antitumor immunity. • Combination of radiotherapy and demethylation agents improves the cytotoxicity of neoantigen-reactive T cells against MSS-CRC. • Neoantigen-reactive T cells and radiotherapy enhance the therapeutic efficacy of neoantigen-based cancer vaccines as well as immunotherapy. [ABSTRACT FROM AUTHOR]