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.

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.

Objective General fatigue is one of the most frequent chief complaints in primary care, and an accurate assessment of fatigue has a direct impact on a patient\'s quality of life and treatment decisions. The Fatigue Assessment Scale (FAS), a measure of general fatigue, is useful for assessing fatigue in diverse cultures and diseases. However, there has been no study showing the reliability and validity of the scale in the Japanese context. The present study assessed the reliability and validity of the Japanese version of the FAS. Methods This study was conducted on 649 patients with long COVID who had a high frequency of general fatigue. To test the structural validity of the FAS, the patients were randomly divided into two groups: one in which an exploratory factor analysis (EFA) was conducted and one in which a confirmatory factor analysis (CFA) was conducted. Cronbach\'s alpha was calculated to assess internal consistency reliability. Results As 58 patients had missing values, we analyzed the data of 591 patients. The EFA led to an FAS comprising two factors. The CFA showed an acceptable fit for this two-factor model. The internal consistency was found to be good (Cronbach\'s alpha =0.89). Conclusion This study verified the structural validity and internal consistency and reliability of the Japanese version of the FAS. The results indicate that the Japanese version of the FAS is useful for assessing general fatigue in patients with long COVID in Japan.

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.

OBJECTIVE: 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).
CONCLUSIONS: 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.

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.

UNASSIGNED: Post-COVID-19 condition (PCC) encompasses long-lasting symptoms in individuals with COVID-19 and is estimated to affect between 31-67% of patients, with women being more commonly affected. No definitive biomarkers have emerged in the acute stage that can help predict the onset of PCC, therefore we aimed at describing sex-disaggregated data of PCC patients from a local cohort and explore potential acute predictors of PCC and neurologic PCC.
UNASSIGNED: A local cohort of consecutive patients admitted with COVID-19 diagnosis between June 2020 and July 2021 were registered, and clinical and laboratory data were recorded. Only those <65 years, discharged alive and followed up at 6 and 12 months after admission were considered in these analyses. Multivariable logistic regression analysis was performed to explore variables associated with PCC (STATA v 18.0).
UNASSIGNED: From 130 patients in the cohort, 104 were contacted: 30% were women, median age of 42 years. At 6 months, 71 (68%) reported PCC symptoms. Women exhibited a higher prevalence of any PCC symptom (87 vs. 60%, p = 0.007), lower ferritin (p = 0.001) and procalcitonin (p = 0.021) and higher TNF levels (p = 0.042) in the acute phase compared to men. Being women was independently associated to 7.60 (95% CI 1.27-45.18, p = 0.026) higher risk for PCC. Moreover, women had lower return to normal activities 6 and 12 months.
UNASSIGNED: Our findings highlight the lasting impact of COVID-19, particularly in young women, emphasising the need for tailored post-COVID care. The lower ferritin levels in women are an intriguing observation, warranting further research. The study argues for comprehensive strategies that address sex-specific challenges in recovery from COVID-19.

Post COVID-19 conditions (PCC) present with a wide range of symptoms. Headache is one of the most frequently reported neurological symptoms by patients with PCC. We aimed to assess the prevalence of headache in patients with PCC who attended the Post-COVIDLMU outpatient department at LMU University Hospital in Munich. We hypothesized that headaches occur more frequently in patients with PCC than in the control group. Patients answered a questionnaire containing sociodemographic characteristics, their current symptoms, and prior psychiatric and somatic diagnoses, the WHO Quality of Life assessment (WHOQOL-BREF), 9-item Patient Health Questionnaire (PHQ-9), and the Fatigue Severity Scale (FSS). 188 PCC patients were included in this study and compared to a control group of patients with a history of COVID-19 or a different infectious disease - but no consecutive post-infectious condition (nc=27). 115 (61%) of our PCC patients were female. The median age was 41 years. 60 (32%, p = 0.001) had a pre-existing psychiatric diagnosis. PCC was associated with worse outcomes in all four domains of the WHOQOL-BREF (p < 0.001), high levels of fatigue (FSS; p < 0.001), and a higher likeliness for symptoms of depression (PHQ-9; p < 0.001). We were able to confirm that psychiatric disorders are more frequently associated with headaches in PCC patients. Headache should be assessed and treated in the context of PCC not only by neurologists but by multi-professional teams and regarding all PCC symptoms.

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UNASSIGNED: This study aimed to assess the association of anxiety, headache, and insomnia on the QoL of patients with long COVID-19.
UNASSIGNED: We conducted a cross-sectional survey between August 2020 and March 2023. A total of 200 participants were eligible, 53 were excluded and 147 patients with long COVID were included. QoL was evaluated across eight domains using the 36-Item Short Form Health Survey (SF-36). Standardized protocols including the Beck Anxiety Inventory (BAI) (n = 103), Pittsburgh Sleep Quality Index (PSQI) (n = 73), and Migraine Disability Assessment (MIDAS) (n = 67) were also used.
UNASSIGNED: Participants with sleep disorders had significantly lower Vitality (p < 0.001). Participants with anxiety disorders had significantly lower Vitality (p = 0.001), poorer Mental Health (p = 0.008), and more severe Bodily Pain (p = 0.008). Participants with headache had significantly lower Vitality (p = 0.032), poorer Mental Health (p = 0.036), and poorer Physical Functioning (p = 0.016). Participants with both headache and anxiety had significantly lower Vitality (p = 0.005) and Mental Health (p = 0.043) domain scores. Correlation analysis revealed that higher scores for anxiety, sleep disorder, and headache were independently correlated with poorer QoL across various domains. The presence of sleep disorder was associated with a fourfold increase in risk of experiencing diminished Vitality (odds ratio [OR]4.47; 95% CI 1.01-19.69; p = 0.048).
UNASSIGNED: Participants with anxiety, sleep, and headache disorders tended to have a worse QoL. The Vitality and Mental Health domains were the most adversely affected in patients with long COVID. Sleep disorders were associated with a fourfold increase in the risk of poor Vitality.