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BACKGROUND: Many patients with post COVID-19 condition (PCC) require healthcare services. However, qualitative studies indicate that patients with PCC encounter many barriers to healthcare access. This cross-sectional study aimed to determine how many PCC patients report barriers to healthcare access and which barriers are reported, and to explore differences between subgroups. METHODS: Data were collected via an online survey from 10,462 adult patients with a confirmed or suspected COVID-19 infection in the Netherlands, who experienced persisting symptoms ≥ 3 months after the initial infection. To study self-perceived barriers, a list of eleven possible barriers was used, covering multiple aspects of healthcare access. Differences between subgroups based on sociodemographic characteristics, medical characteristics, PCC symptoms (fatigue, dyspnoea, cognitive problems, anxiety and depression), and healthcare use (general practitioner, paramedical professional, medical specialist, occupational physician and mental health professional) were studied through multivariable multinomial (0 vs. 1 vs. > 1 barrier) and binomial regression analyses (for each individual barrier). RESULTS: A total of 83.2% of respondents reported at least one barrier to healthcare access. Respondents reported a median of 2.0 (IQR = 3.0) barriers. The barriers "I didn't know who to turn to for help" (50.9%) and "No one with the right knowledge/skills was available" (36.8%) were most frequently reported. Respondents with younger age, higher educational level, not hospitalized during acute COVID-19 infection, longer disease duration, who had more severe PCC symptoms, and who did not consult an occupational physician or paramedical professional, were more likely to report barriers. Analyses per barrier showed that women were more likely to report financial and help-seeking barriers, while men were more likely to report barriers related to availability of care. Hospitalized respondents were less likely to report barriers related to availability of care, but not less likely to report financial or help-seeking barriers. CONCLUSIONS: This study shows that the majority of patients with PCC experiences barriers to healthcare access. Particular attention should be paid to younger, non-hospitalized patients with a long disease duration and severe PCC symptoms. Efforts to remove barriers should focus not only on improving availability of care, but also on helping patients navigate care pathways.

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Background: Individuals affected by the post-covid condition (PCC) show an increased fatigue and the so-called post-exertion malaise (PEM) that led health professionals to advise against exercise although accumulating evidence indicates the contrary. The goal of this study is to determine the impact of a closely monitored 8-week mixed exercise program on physical capacity, symptoms, fatigue, systemic oxidative stress and plasma proteomic profiles of PCC cases. Methods: Twenty-five women and men with PCC were assigned sequentially to exercise (n = 15) and non-exercise (n = 10) groups. Individuals with no PCC served as a control group. The exercise program included cardiovascular and resistance exercises. Physical capacity, physical activity level and the presence of common PCC symptoms were measured before and after the intervention. Fatigue was measured the day following each exercise session. Plasma and PBMC samples were collected at the beginning and end of the training program. Glutathione and deoxyguanosine levels in PBMC and plasma proteomic profiles were evaluated. Results: Bicep Curl (+15% vs 4%; p = 0.040) and Sit-to-Stand test (STS-30 (+31% vs +11%; p = 0.043)) showed improvement in the exercise group when compared to the non-exercise group. An interaction effect was also observed for the level of physical activity (p =0.007) with a positive effect of the program on their daily functioning and without any adverse effects on general or post-effort fatigue. After exercise, glutathione levels in PBMCs increased in women but remained unchanged in men. Discernable changes were observed in the plasma proteomics profile with certain proteins involved in inflammatory response decreasing in the exercise group. Conclusions: Supervised exercise adapted to the level of fatigue and ability is safe and effective in PCC patients in improving their general physical capacity and wellbeing. Systemic molecular markers that accompany physical improvement can be monitored by analyzing plasma proteomics and markers of oxidative stress. Large-scale studies will help identify promising molecular markers to objectively monitor patient improvement.

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This systematic review aimed to investigate the prevalence of symptoms of post-COVID-19 condition (long COVID), in children hospitalized with COVID-19. We searched PUBMED and EMBASE on 15 March, 2023, using search strategy: "long COVID" OR "post-COVID-19" OR "postacute COVID-19" OR "long-term COVID" OR "COVID-19 sequelae" OR "persistent COVID-19" OR "chronic COVID-19". We included observational studies (case-control, cross-sectional, cohort, or case series) that investigated symptoms of post-COVID-19 condition (long COVID) in children (<18 years) admitted with COVID-19. We used the WHO case definition of post-COVID-19 condition. Long COVID was defined as persistence of otherwise unexplained symptoms for at least three months after SARS-CoV-2 infection. We used the command "metaprop" to perform random-effects meta-analysis. Eleven studies involving 2279 patients were included. In the period between ≥3 months and <12 months after acute COVID-19, the most frequent symptom was exercise intolerance with a pooled prevalence of 29% (95% CI: 7%-57%, I2 = 95%), followed by nonspecific respiratory symptoms (12%, 95% CI: 0%-48%, I2 = 0%), psychological disorders (10%, 95% CI: 1%-25%, I2 = 97%), and nonspecific gastrointestinal symptoms (10%, 95% CI: 0%-37%, I2 = 99%). In the period ≥12 months after the initial infection, the pooled prevalence of post COVID symptoms was lower, with 6% (95% CI: 2%-10%, I2 = 83%) for exercise intolerance and 3% (95% CI: 0%-8%, I2 = 89%) for fatigue. In conclusion, symptoms of post-COVID condition (long COVID) in hospitalized children affect multiple organ systems, with higher prevalence in the period up to 12 months after the acute phase of COVID-19.

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Purpose: New-onset chronic musculoskeletal (MSK) pain is one of the common persistent symptoms in Long COVID (LC). This study investigated its clinical characteristics, underlying mechanisms, and impact on function, psychological health, and quality of life. Patients and Methods: Thirty adults (19 female, 11 male) with LC and new-onset chronic MSK pain underwent clinical examination, Quantitative Sensory Testing (QST), and blood tests for inflammatory markers and completed the following outcome measures: Timed Up and Go test (TUG), handgrip strength test, COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), Brief Pain Inventory (BPI), Pain Self-Efficacy Questionnaire (PSEQ), Pain Catastrophizing Scale (PCS), International Physical Activity Questionnaire-short form (IPAQ-sf), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and EuroQol Five Dimensions health-related quality of life (EQ-5D-5L). Results: New-onset chronic MSK pain was widespread and continuous in nature, and worse in the joints. When compared to normative values reported in the literature: a) QST revealed mechanical hyperalgesia, heightened temporal summation of pain, and hypoesthesia to vibration stimuli, which is strongly suggestive of central sensitization; b) Plasma cytokine assays indicated distinct pro-inflammatory profiles; c) TUG time indicated reduced balance and mobility; d) handgrip strength revealed general weakness; e) physical activity was lower; and f) there were moderate levels of depression and anxiety with lower self-efficacy scores and lower levels of pain catastrophizing. LC symptoms were of moderate severity (44.8/100), moderate functional disability (22.8/50) and severely compromised overall health (2.6/10) when compared to pre-COVID scores. Conclusion: New-onset chronic MSK pain in LC tends to be widespread, constant, and associated with weakness, reduced function, depression, anxiety, and reduced quality of life. There is associated central sensitization and proinflammatory state in the condition. Further research is essential to explore the longitudinal progression and natural evolution of the new-onset chronic MSK pain in LC.

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INTRODUCTION: Long COVID (LC) occurs when people experience symptoms for weeks, months or even years after a COVID-19 infection. This review looks at research exploring the LC definitions, prevalence, symptoms, risk factors, and associated impacts in research on healthcare workers (HCWs). DATA SOURCES: We systematically searched five electronic databases (CINAHL, EMBASE, Medline, PsycInfo and PubMed) and compiled a narrative literature review based on 56 relevant studies. AREAS OF AGREEMENT: LC is prevalent among HCWs who become infected by COVID-19. Many of the most frequent symptoms associated with LC in the general population are also reported among HCWs. Some risk factors for LC are also similar to those in the general population, such as female sex, older age, and having a pre-existing respiratory illness. AREAS OF CONTROVERSY: The mechanism(s) responsible for LC remains unknown. A variety of terms, timeframes and symptoms are used to define LC, creating difficulties in comparing results across studies. Much of the research is cross-sectional and fails to explore the impacts that prolonged symptoms have on HCWs' personal and professional lives. GROWING POINTS: The need to support HCWs with LC is clear. Identifying the mechanism(s) responsible for LC is a key priority, as this will inform treatments. AREAS FOR DEVELOPING RESEARCH: Future research should move towards a standard definition for LC. Greater attention should be paid to longitudinal and qualitative studies, which could give insights into prognosis, lived experience and work participation. Finally, studies evaluating treatments suitable for people with LC are timely.

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Post COVID-19 Condition (PCC) is a clinical syndrome following COVID-19 disease. PCC symptoms in adults entail significant productivity loss and reduced quality of life. This study aimed at estimating the epidemiological and economic burden of PCC among the working-age population of Italy and the US. This ecological analysis was conducted on data from January 2020 to April 2023, regarding population aged 18-64. PCC incidence for the US was retrieved from publicly reported estimates, while for Italy it was estimated from COVID-19 cases. Prevalence of factors associated with PCC and parameters to calculate temporary productivity losses (TPL) were retrieved. An estimated incidence rate ratio (eIRR) of PCC incidence in Italy and the US was calculated. TPL for reduced earnings and total quality-adjusted life years (QALYs) lost were also estimated. The ecological eIRR Italy/US was 0.842 [95%CI 0.672-1.015], suggesting that, holding COVID-19 cases constant, 15.8% fewer PCC cases have occurred in Italy compared to the US. Overall PCC cases were found to be 12.0 [95%CI 9.9-14.1] million in the US, with 1.9 [95%CI 1.6-2.3] million QALYs lost, and 2.4 [95%CI 1.8-3.0] million in Italy, with 0.4 [95%CI 0.3-0.5] million QALYs lost. Up to April 2023, the TPL was estimated to be Int$7.5 [95%CI 5.8-10.1] billion in Italy and $41.5 [95%CI 34.3-48.7] billion in the US. PCC has had a significant epidemiological and economic impact on the working-age population. The findings from this study may be of use for health planning and policy regarding PCC in working-age adults.

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OBJECTIVE: Post COVID-19 condition is characterized by persistent symptoms after COVID-19 with yet unknown etiology. To explore whether media-related nocebo effects potentially contribute to post COVID-19 condition, we studied in an observational cohort whether frequencies of media coverage of symptoms after COVID-19 corresponded with prevalence rates of these symptoms in participants from a general population cohort diagnosed with COVID-19. METHODS: Prevalence rates and typology of symptoms after COVID-19 in the general population (N = 4231), adjusted for prevalence rates in a matched non-infected control population (n = 8462) were calculated by using data on 23 symptoms from the Lifelines COVID-19 Cohort collected between March 2020 and August 2021. Media coverage of post COVID-19 condition was assessed by coding 1266 Dutch post COVID-19-related news articles (inter-rater-κ ≥ 0.75), published during the corresponding timeframe. Herein, we assessed whether the same 23 symptoms were mentioned as being related to post COVID-19 condition. RESULTS: Core post COVID-19 condition symptoms were mentioned in 390 (30.8%) articles. Five of the ten core symptoms were mentioned by 10 or fewer articles. Ageusia/anosmia was most often persistently increased in COVID-19-positive participants (7.6%), yet was mentioned in 80 (6.3%) articles. General tiredness and breathing difficulties were frequently mentioned, in 23.9% and 17.1% of the articles respectively, while these were not the most frequently increased symptoms reported by participants (4.9% and 2.4%). CONCLUSION: If post COVID-19 condition was predominantly attributable to nocebo effects, its symptom profile would be expected to reflect levels of media coverage for symptoms after COVID-19. However, our findings do not support this.

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The protracted form of COVID-19 known as 'long covid' was first described in 2020. Its symptoms, course and prognosis vary widely; some patients have a multi-system, disabling and prolonged illness. In 2021, ring-fenced funding was provided to establish 90 long covid clinics in England; some clinics were also established in Scotland and Wales. The NIHR-funded LOCOMOTION project implemented a UK-wide quality improvement collaborative involving ten of these clinics, which ran from 2021 to 2023. At regular online meetings held approximately 8-weekly, participants prioritised topics, discussed research evidence and guidelines, and presented exemplar case histories and clinic audits. A patient advisory group also held a priority-setting exercise, participated in quality meetings and undertook a service evaluation audit. The goal of successive quality improvement cycles aimed at changing practice to align with evidence was sometimes hard to achieve because definitive evidence did not yet exist in this new condition; many patients had comorbidities; and clinics were practically constrained in various ways. Nevertheless, much progress was made and a series of 'best practice' guides was produced, covering general assessment and management; breathing difficulties; orthostatic tachycardia and other autonomic symptoms; fatigue and cognitive impairment; and vocational rehabilitation. This paper summarises key findings with the frontline clinician in mind.

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Introduction: Adults with Post-COVID-19 Condition (PCC) may show cognitive impairments in attention, processing speed, memory, and executive function. Multimodal programs that combine cognitive training, physical activity and emotional tasks, such as mindfulness-based interventions (MBIs), may offer a suitable alternative for improving PCC treatments. Immersive Virtual Reality (IVR) is a promising technology that can enhance traditional cognitive training, physical activity, and MBIs. The use of IVR technology may increase engagement with these interventions and potentially enhance the individual benefits of cognitive training, exercise and MBIs. The current study evaluated the impact of a multimodal IVR intervention, comparing this with a usual care intervention (control group), in order to assess changes in cognition and mental health in adults with PCC. We also aimed to assess user experience factors such as enjoyment, perceived improvement, and fatigue following each multimodal IVR session within the experimental group. Method: Thirty-one participants with PCC symptoms were assigned to either the experimental group (IVR, n = 15) or the control group (usual care intervention, n = 16) in a quasi-experimental design study. The multimodal IVR intervention consisted of MBI, cognitive training and physical exercise and was delivered in a 60-min group session with 5 participants, twice a week, for 8 weeks (16 sessions in total). Measures of global cognition, attention, processing speed, verbal episodic memory and subjective memory complaints (primary measures), and depressive and anxiety symptoms and fatigue (secondary measures) were assessed at baseline and also after 8 weeks (post-intervention). Results: Mixed between-group (group) and within-group (pre-post assessments) ANOVAs revealed significant group*time interactions in global cognition, simple attention, processing speed, memory and depressive symptoms, with large effect sizes (p < 0.05; partial η2 > 0.14). There was also a marginally significant group*time interaction for executive function (p = 0.05). Follow-up analyses comparing pre-and post-intervention outcomes for each group separately showed that the experimental group significantly improved in global cognition, processing speed, memory and depressive symptoms, while the control group showed no significant pre-post changes. Friedman tests showed a significant main effect of time (χ2(2) = 6.609, p = 0.04), with a gradual increase in enjoyment from the first, to the mid, and then to the final session. In addition, perceived improvement scores remained high throughout the intervention, and patient-reported fatigue levels did not fluctuate significantly throughout the intervention. Conclusion: To our knowledge, no previous research has combined cognitive training, physical exercise and MBI using an IVR paradigm in adults with PCC. Despite their inherent limitations, our findings mark a pioneering step toward improving cognition and mental health outcomes in PCC through the innovative use of new technology and multimodal approaches. This first study should be accompanied by more extensive, randomized clinical trials aimed at further exploring and refining these interventions.

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Post-COVID-19 condition is recognized as a multifactorial disorder, with persistent presence of viral antigens, discordant immunity, delayed viral clearance, and chronic inflammation. Obesity has emerged as an independent risk factor for both SARS-CoV-2 infection and its subsequent sequelae. In this study, we aimed to predict the molecular mechanisms linking obesity and post-COVID-19 distress. Viral antigen-exposed adipose tissues display remarkable levels of viral receptors, facilitating viral entry, deposition, and chronic release of inflammatory mediators and cells in patients. Subsequently, obesity-associated inflammatory insults are predicted to disturb cellular and humoral immunity by triggering abnormal cell differentiation and lymphocyte exhaustion. In particular, the decline in SARS-CoV-2 antibody titers and T-cell exhaustion due to chronic inflammation may account for delayed virus clearance and persistent activation of inflammatory responses. Taken together, obesity-associated defective immunity is a critical control point of intervention against post-COVID-19 progression, particularly in subjects with chronic metabolic distress.

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Long COVID is a common sequela of SARS-CoV-2 infection. Data from numerous scientific studies indicate that long COVID involves a complex interaction between pathophysiological processes. Long COVID may involve the development of new diagnosable health conditions and exacerbation of pre-existing health conditions. However, despite this rapidly accumulating body of evidence regarding the pathobiology of long COVID, psychogenic and functional interpretations of the illness presentation continue to be endorsed by some healthcare professionals, creating confusion and inappropriate diagnostic and therapeutic pathways for people living with long COVID. The purpose of this perspective is to present a clinical and scientific rationale for why long COVID should not be considered as a functional neurologic disorder. It will begin by discussing the parallel historical development of pathobiological and psychosomatic/sociogenic diagnostic constructs arising from a common root in neurasthenia, which has resulted in the collective understandings of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and functional neurologic disorder (FND), respectively. We will also review the case definition criteria for FND and the distinguishing clinical and neuroimaging findings in FND vs. long COVID. We conclude that considering long COVID as FND is inappropriate based on differentiating pathophysiologic mechanisms and distinguishing clinical findings.

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Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.

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Purpose: The present study aimed to clarify the effects of a hyperglycemic condition on the clinical consequences of long COVID. Methods: Among 643 patients who visited the outpatient clinic of our hospital from February 2021 to September 2023, long COVID patients were classified into a hyperglycemic (HG) group with casual blood glucose levels above 140 mg/dL and a normoglycemic (NG) group. The patients' backgrounds, clinical symptoms, health status including the QOL evaluation scale (EQ-5D-5L), self-rating depression scale (SDS), and F-scale questionnaire (FSSG), blood test data, and recovery periods were analyzed. Results: The NG group included 607 patients with long COVID and the HG group included 36 patients with long COVID. Patients in the HG group were older than those in the NG group (55 vs. 41 years; p < 0.001) and included a larger percentage of males (67% vs. 44%; p = 0.009). The HG group had a larger percentage of patients with moderate-to-severe conditions in the acute infection phase (28% vs. 12%; p = 0.008), a higher BMI (25 vs. 22 kg/m2; p < 0.001), higher blood pressure (138/81 vs. 122/72 mmHg; p < 0.001), and a larger percentage of patients with an alcohol drinking habit (53% vs. 34%; p = 0.031). Long COVID symptoms and self-rated scales were not differed between the two groups; however, the laboratory data showed that liver and renal functions and metabolic data were significantly worse in the HG group. Although there was no apparent difference between the two groups in duration from the infection to the first visit, the HG group had a significantly longer period of recovery from long COVID (median period of 421 vs. 294 days; p = 0.019). Conclusion: A hyperglycemic state associated with other lifestyle-related diseases is associated with the prolongation of recovery from long COVID.

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BACKGROUND: The study aimed to evaluate the prevalence and pattern of long COVID-19 (LC) symptoms among individuals who had contracted COVID-19, to calculate the incidence of LC, and to provide insights into risk factors associated with developing LC in this population. METHODS: This population-based cross-sectional survey was conducted in Fars province in 2023. Adult participants with a history of COVID-19 were recruited using a cluster random sampling method, alongside a control group with similar characteristics through the same methodology. Data were collected through in-person interviews using two researcher-developed data collection forms focused on demographic and clinical information. RESULTS: A total of 2010 participants, comprising 1561 (77.7%) and 449 (22.3%) individuals with and without a previous history of COVID-19 were included. Among those with COVID-19 history, the prevalence of experiencing any symptoms was 93.7% (95% CI of 92.3%-94.8%) during the disease acute phase and 36.4% (95% CI of 34.0%-38.8%) after recovery. The incidence of symptoms specifically related to COVID-19, calculated by comparing the symptom rates between participants with and without a history of COVID-19, was found to be 13%. Factors such as older age, previous hospitalization for COVID-19, presence of cardiovascular disease, and use of steroids/chemotherapy were associated with LC symptoms. CONCLUSIONS: Our investigation sheds light on long-term aspects of COVID-19, demonstrating a significant prevalence of LC with diverse manifestations. It also underscores the importance of establishing standardized criteria and control groups in research on LC to address challenges related to heterogeneity and potential overestimation of symptoms.

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Altered body composition and cytokine production due to SARS-CoV-2 antigens may affect homeostasis model assessment for insulin resistance (HOMA-IR) after SARS-CoV-2 infection. To elucidate this phenomenon, we conducted a longitudinal study involving 47 COVID-19 patients, who were followed up for 12 months. During recruitment, body composition and glucose indices were measured, and heparin blood samples were collected for measuring cytokine production. HOMA-IR was considered an elevated or non-elevated group based on the ratio between HOMA-IR at 12 months and 1 month of convalescence. Those with elevated HOMA-IR had a significantly higher body mass index, body fat percentage, and visceral fat rating and had a lower lean mass and lean/fat mass ratio than their counterparts. During the convalescent period, the elevated HOMA-IR group had lower TNFα, IFNγ, IL-2, IL-10, and granzyme B expression levels but had higher TNFα/IL-10, IFNγ/IL-10, IL-2/IL-10, and granzyme B/IL-10 ratios than the other group. The reduced cytokine production and pro-/anti-inflammatory imbalance in patients with elevated HOMA-IR may suggest immune cell dysfunction toward SARS-CoV-2. Patients with elevated HOMA-IR after SARS-CoV-2 infection may experience an increase in BMI and body fat percentage, leading to increased immune dysfunction and chronic inflammatory condition. A nutritional approach and promotion of physical activity may help reduce HOMA-IR and ameliorate glucose indices in these patients.

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BACKGROUND: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA). METHODS: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses. RESULTS: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; ß=-0.018, p=.035), except in the QFS group (ß=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658). CONCLUSION: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels.

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This exploratory analysis of the double-blind, phase 3, SCORPIO-SR trial assessed the effect of ensitrelvir in preventing post coronavirus disease 2019 (COVID-19) condition (PCC). Patients with mild-to-moderate COVID-19 were randomized (1:1:1) within 120 h of symptom onset; received 5-day oral ensitrelvir 125 mg (375 mg on day 1), 250 mg (750 mg on day 1), or a matching placebo once daily; and were assessed for the severity of typical PCC symptoms using a self-administered questionnaire. In total, 341, 317, and 333 patients were assessed in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively (mean age, 35.6-36.5 years; men, 53.3%-58.3%). On days 85, 169, and 337, ensitrelvir 125-mg treatment showed 32.7% (95% confidence interval [CI]: -30.6, 66.1), 21.5% (95% CI: -37.3, 55.6), and 24.6% (95% CI: -43.7, 60.9) reductions versus placebo, respectively, in the risk of any of the 14 acute-phase COVID-19 symptoms (at least one mild, moderate, or severe symptom with general health not returning to the usual level). Ensitrelvir 250-mg treatment showed 10.9% (95% CI: -67.0, 52.8), 9.5% (95% CI: -56.6, 48.0), and 30.6% (95% CI: -36.2, 65.5) risk reductions versus placebo on days 85, 169, and 337, respectively. Risk reductions were observed in any of the 4 neurological symptoms and were more pronounced among patients with high acute-phase symptom scores at baseline and among those with a baseline body mass index ≥25 kg/m2. Ensitrelvir treatment in the acute phase of COVID-19 may reduce the risk of various symptoms associated with PCC. TRIAL REGISTRATION NUMBER: jRCT2031210350.

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PURPOSE: Post COVID-19 Condition (PCC), being persistent COVID-19 symptoms, is reminiscent of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-a chronic multi-systemic illness characterised by neurocognitive, autonomic, endocrinological and immunological disturbances. This novel cross-sectional investigation aims to: (1) compare symptoms among people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) to inform developing PCC diagnostic criteria; and (2) compare health outcomes between patients and people without acute or chronic illness (controls) to highlight the illness burdens of ME/CFS and PCC. METHODS: Sociodemographic and health outcome data were collected from n = 61 pwME/CFS, n = 31 pwPCC and n = 54 controls via validated, self-administered questionnaires, including the 36-Item Short-Form Health Survey version 2 (SF-36v2) and World Health Organization Disability Assessment Schedule version 2.0 (WHODAS 2.0). PwME/CFS and pwPCC also provided self-reported severity and frequency of symptoms derived from the Canadian and International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC. RESULTS: Both illness cohorts similarly experienced key ME/CFS symptoms. Few differences in symptoms were observed, with memory disturbances, muscle weakness, lymphadenopathy and nausea more prevalent, light-headedness more severe, unrefreshed sleep more frequent, and heart palpitations less frequent among pwME/CFS (all p < 0.05). The ME/CFS and PCC participants' SF-36v2 or WHODAS 2.0 scores were comparable (all p > 0.05); however, both cohorts returned significantly lower scores in all SF-36v2 and WHODAS 2.0 domains when compared with controls (all p < 0.001). CONCLUSION: This Australian-first investigation demonstrates the congruent and debilitating nature of ME/CFS and PCC, thereby emphasising the need for multidisciplinary care to maximise patient health outcomes.

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Since the emergence of the SARS-CoV-2 virus in 2019, nearly 700 million COVID-19 cases and 7 million deaths have been reported globally. Despite most individuals recovering within four weeks, the Center for Disease Control (CDC) estimates that 7.5% to 41% develop post-acute infection syndrome (PAIS), known as 'Long COVID'. This review provides current statistics on Long COVID's prevalence, explores hypotheses concerning epidemiological factors, such as age, gender, comorbidities, initial COVID-19 severity, and vaccine interactions, and delves into potential mechanisms, including immune responses, viral persistence, and gut dysbiosis. Moreover, we conclude that women, advanced age, comorbidities, non-vaccination, and low socioeconomic status all appear to be risk factors. The reasons for these differences are still not fully understood and likely involve a complex relationship between social, genetic, hormonal, and other factors. Furthermore, individuals with Long COVID-19 seem more likely to endure economic hardship due to persistent symptoms. In summary, our findings further illustrate the multifaceted nature of Long COVID and underscore the importance of understanding the epidemiological factors and potential mechanisms needed to develop effective therapeutic strategies and interventions.

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