Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study.

BACKGROUND: In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort. METHODS: In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found. RESULTS: According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients. CONCLUSIONS: This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.

Insomnia and sleep characteristics in post COVID-19 fatigue: A cross-sectional case-controlled study.

OBJECTIVE: Following COVID-19 many patients report persistent fatigue and insomnia. Given the overlapping features, insomnia can be underdiagnosed in post-COVID-19 fatigue patients. This study aimed to determine insomnia severity, prevalence of clinical insomnia and sleep characteristics of post-COVID-19 fatigue patients. Data of post-COVID-19 fatigue patients were compared with those of patients with chronic fatigue syndrome (ME/CFS), a condition resembling post-COVID-19 fatigue. METHODS: In this cross-sectional case-controlled study, insomnia severity, assessed with the Insomnia Severity Index (ISI), and prevalence of clinical insomnia (ISI score ≥ 10), were determined in patients with post-COVID-19 fatigue (n = 114) and compared with ME/CFS (n = 59) using ANCOVA and logistic regression, respectively. Linear regression analyses were used to evaluate whether mood, concentration problems, pain, fatigue (assessed with questionnaires) and diagnosis were associated with insomnia. Sleep characteristics were determined with a sleep diary and accelerometer in post-COVID-19 fatigue and compared with ME/CFS using ANCOVA. RESULTS: In patients with post-COVID-19 fatigue mean (SD) insomnia severity was 11.46 (5.7) and 64% reported clinical insomnia. Insomnia severity was significantly associated with depressive symptoms (ß = 0.49, p = 0.006) and age (ß = 0.08, p = 0.04). The mean (SD) subjective sleep duration was 7.4 (1.0) hours with a sleep efficiency of 82 (11)%. Several subjective sleep characteristics of the post-COVID-19 fatigue patients differed from ME/CFS patients; only sleep duration, being significantly shorter in post-COVID-19 fatigue patients (p = 0.003), seemed clinically relevant (d = 0.58). CONCLUSION: Insomnia severity and prevalence of clinical insomnia are high in patients with post-COVID-19 fatigue. Insomnia should be assessed and if present treated with insomnia focused therapy.

Increased risk of chronic fatigue syndrome following infection: a 17-year population-based cohort study.

BACKGROUND: Previous serological studies have indicated an association between viruses and atypical pathogens and Chronic Fatigue Syndrome (CFS). This study aims to investigate the correlation between infections from common pathogens, including typical bacteria, and the subsequent risk of developing CFS. The analysis is based on data from Taiwan's National Health Insurance Research Database. METHODS: From 2000 to 2017, we included a total of 395,811 cases aged 20 years or older newly diagnosed with infection. The cases were matched 1:1 with controls using a propensity score and were followed up until diagnoses of CFS were made. RESULTS: The Cox proportional hazards regression analysis was used to estimate the relationship between infection and the subsequent risk of CFS. The incidence density rates among non-infection and infection population were 3.67 and 5.40 per 1000 person-years, respectively (adjusted hazard ratio [HR] = 1.5, with a 95% confidence interval [CI] 1.47-1.54). Patients infected with Varicella-zoster virus, Mycobacterium tuberculosis, Escherichia coli, Candida, Salmonella, Staphylococcus aureus and influenza virus had a significantly higher risk of CFS than those without these pathogens (p < 0.05). Patients taking doxycycline, azithromycin, moxifloxacin, levofloxacin, or ciprofloxacin had a significantly lower risk of CFS than patients in the corresponding control group (p < 0.05). CONCLUSION: Our population-based retrospective cohort study found that infection with common pathogens, including bacteria, viruses, is associated with an increased risk of developing CFS.

Occupation-Induced Fatigue and Impacts on Emergency First Responders: A Systematic Review.

Fatigue in emergency first responders (EFRs) is known to affect performance abilities and safety outcomes for both patients and EFRs. The primary aim of this review was to determine the main contributors to occupation-induced fatigue in EFRs and its subsequent impacts. Following the PRIMSA checklist, academic databases (Medline, Embase, CINAHL, and SPORTDiscus) were searched using key terms with results subjected to inclusion and exclusion criteria. Populations of interest were firefighters, paramedics, or emergency call centre personnel. Of the 5633 records identified, 43 studies, which reported on 186 unique measures from a total population of 6373 participants, informed the review. Synthesis revealed fatigue was caused by lack of sleep during the shift and consistent poor sleep quality which negatively impacted cognitive function, alertness, and physical and mental health while increasing safety-compromising behaviours and injuries. Both subjective and objective assessments of fatigue are necessary for effective risk management in EFRs. EFRs that are consistently fatigued are at a greater risk of poor physical and mental health, reduced cognitive function, and increased injuries. No studies reported on fatigue in emergency call centre personnel, highlighting a literature gap. Funding was provided by the Australian Capital Territory Emergency Services Agency. Preregistration was filed in OSF: osf.io/26f3s.

A systematic review and meta-analysis of urinary biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness that affects many body systems including the immune, nervous, endocrine, cardiovascular, and urinary systems. There is currently no universal diagnostic marker or targeted treatment for ME/CFS. Urine is a non-invasive sample that provides biomarkers that may have the potential to be used in a diagnostic capacity for ME/CFS. While there are several studies investigating urine-based biomarkers for ME/CFS, there are no published systematic reviews to summarise existing evidence of these markers. The aim of this systematic review was to compile and appraise literature on urinary-based biomarkers in ME/CFS patients compared with healthy controls. METHODS: Three databases: Embase, PubMed, and Scopus were searched for articles pertaining to urinary biomarkers for ME/CFS compared with healthy controls published between December 1994 to December 2022. The final articles included in this review were determined through application of specific inclusion and exclusion criteria. Quality and bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. A meta-analysis according to Cochrane guidelines was conducted on select studies, in particular, those that investigate urinary free cortisol levels in ME/CFS patients compared to healthy controls using the program STATA 17. RESULTS: Twenty-one studies were included in this review. All of the studies investigated urinary-based markers in ME/CFS patients compared with healthy controls. The reported changes in urinary outputs include urinary free cortisol (38.10%), carnitine (28.6%), iodine (4.76%), and the metabolome (42.86%). In most cases, there was minimal overlap in the main outcomes measured across the studies, however, differences in urinary free cortisol between ME/CFS patients and healthy controls were commonly reported. Seven studies investigating urinary free cortisol were included in the meta-analysis. While there were significant differences found in urinary free cortisol levels in ME/CFS patients, there was also substantial heterogeneity across the included studies that makes drawing conclusions difficult. CONCLUSIONS: There is limited evidence suggesting a consistent and specific potential urinary-based biomarker for ME/CFS. Further investigations using more standardised methodologies and more stringent case criteria may be able to identify pathophysiological differences with diagnostic potential in ME/CFS patients compared with healthy controls.

Incidence and contributing factors of non-root canal treated teeth with chronic fatigue root fracture: A cross-sectional study.

BACKGROUND/PURPOSE: Chronic fatigue root fracture describes a root fracture in a non-root canal treated (non-RCT) tooth. This study aimed to report the incidence and contributing factors of non-RCT teeth with chronic fatigue root fracture in a Taiwanese population. METHODS: This cross-sectional study included teeth extracted at Taipei Veterans General Hospital in Taiwan between 2018 and 2019. The reasons for extractions were recorded and included vertical and horizontal root fractures (VRF and HRF). Comparisons of clinical factors between teeth with fatigue VRF and teeth with fatigue HRF were performed by chi-square or Fisher exact test, where appropriate. RESULTS: Of the 4207 extracted teeth examined, 263 (6.25%) had tooth fracture. Thirty-two non-RCT teeth had chronic fatigue root fracture, including 16 with VRF and 16 with HRF. The incidence was 0.76% (32/4207). The occurrence of chronic fatigue root fracture was higher in males (83.9%). The mean age of the 31 patients with chronic fatigue root fracture was 71.7 ± 13.1 years. More than half of these teeth had intact crowns with severe attrition. The fatigue VRF occurred more frequently in molars (P = 0.003), in roots with a long oval cross-section (P = 0.037), and in terminal teeth (P = 0.013) than the fatigue HRF. CONCLUSION: The incidence of chronic fatigue root fracture is 0.76%. Both VRF and HRF occur mainly in aged males, in posterior teeth with attrition, and in teeth without restoration. Tooth position, cross-section root morphology, and terminal tooth are contributing factors related to chronic fatigue root fracture.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Comorbidities: Linked by Vascular Pathomechanisms and Vasoactive Mediators?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often associated with various other syndromes or conditions including mast cell activation (MCA), dysmenorrhea and endometriosis, postural tachycardia (POTS) and small fiber neuropathy (SFN). The causes of these syndromes and the reason for their frequent association are not yet fully understood. We previously published a comprehensive hypothesis of the ME/CFS pathophysiology that explains the majority of symptoms, findings and chronicity of the disease. We wondered whether some of the identified key pathomechanisms in ME/CFS are also operative in MCA, endometriosis and dysmenorrhea, POTS, decreased cerebral blood flow and SFN, and possibly may provide clues on their causes and frequent co-occurrence. Our analysis indeed provides strong arguments in favor of this assumption, and we conclude that the main pathomechanisms responsible for this association are excessive generation and spillover into the systemic circulation of inflammatory and vasoactive tissue mediators, dysfunctional ß2AdR, and the mutual triggering of symptomatology and disease initiation. Overall, vascular dysfunction appears to be a strong common denominator in these linkages.

Psychiatric disorders comorbid with general medical illnesses and functional somatic disorders: The Lifelines cohort study.

OBJECTIVE: It is not clear why psychiatric disorders are more prevalent in the functional somatic syndromes than other general medical illnesses. This study assessed the correlates of psychiatric disorders in 3 functional syndromes and 3 general medical illnesses in a population-based sample. METHODS: The Lifelines cohort study included 122,366 adults with relevant data for 6 self-reported conditions: irritable bowel syndrome (IBS), fibromyalgia, chronic fatigue syndrome (CFS), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and diabetes. For each condition the proportion with a DSM-IV psychiatric disorder was assessed. In a cross-sectional design, logistic regression identified at baseline the variables most closely associated with current psychiatric disorder in participants with a pre-existing medical or functional condition. In a separate analysis the prevalence of psychiatric disorder prior to onset of these conditions was assessed. This was a longitudinal study with psychiatric disorder assessed at baseline in participants who subsequently developed a general medical or functional condition between baseline and follow-up. RESULTS: The prevalence of psychiatric disorder was higher (17-27%) in the functional somatic syndromes than the general medical illnesses (10.4-11.7%). The variables closely associated with psychiatric disorder were similar in the functional syndromes and general medical illnesses: stressful life events, chronic personal health difficulties, neuroticism, poor perception of general health, impairment of function due to physical illness and reported previous (lifetime) psychiatric disorder. The prevalence of psychiatric disorder prior to development of these disorder was similar to that of established disorders. CONCLUSION: Despite the difference in prevalence, the correlates of psychiatric disorders were similar in functional and general medical disorders and included predisposing and environmental factors. The increased rate of psychiatric disorder in functional somatic syndromes appears to be evident before onset of the syndrome.

Do diagnostic criteria for ME matter to patient experience with services and interventions? Key results from an online RDS survey targeting fatigue patients in Norway.

Public health and welfare systems request documentation on approaches to diagnose, treat, and manage myalgic encephalomyelitis and assess disability-benefit conditions. Our objective is to document ME patients' experiences with services/interventions and assess differences between those meeting different diagnostic criteria, importantly the impact of post-exertional malaise. We surveyed 660 fatigue patients in Norway using respondent-driven sampling and applied validated DePaul University algorithms to estimate Canadian and Fukuda criteria proxies. Patients on average perceived most interventions as having low-to-negative health effects. Responses differed significantly between sub-groups for some key interventions. The PEM score was strongly associated with the experience of most interventions. Better designed and targeted interventions are needed to prevent harm to the patient group. The PEM score appears to be a strong determinant and adequate tool for assessing patient tolerance for certain interventions. There is no known treatment for ME, and "do-no-harm" should be a guiding principle in all practice.

My experience with ME/CFS and implications: A personal narrative.

 Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating health condition characterized by overwhelming fatigue and post-exertional malaise, or exacerbation of symptoms following physical, mental, or emotional exertion. ME/CFS often impacts every aspect of an individual's life, and one's new reality may be much different from the daily life experienced before the onset of the condition. Though the long-term effects of COVID-19 have brought increased attention to chronic fatigue and related disorders, ME/CFS is still vastly understudied and frequently misunderstood. People with ME/CFS are often passed between various healthcare providers as evidence-based treatments remain scarce. These patients are sometimes sent to rehabilitation professionals, who often lack appropriate education and experience with this patient population. This article describes the experience of a young woman and physical therapist with ME/CFS following COVID-19 infection, as well as potential implications for rehabilitation professionals and those who care for those with this condition.

Coping strategies in patients with good outcome but chronic fatigue after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Fatigue is a highly prevalent and debilitating symptom among patients in the chronic phase of aneurysmal subarachnoid haemorrhage (aSAH) with no identified effective treatment. Cognitive therapy has been shown to have moderate effects on fatigue. Delineating the coping strategies used by patients with post-aSAH fatigue and relating them to fatigue severity and emotional symptoms could be a step towards developing a behavioural therapy for post-aSAH fatigue. METHODS: Ninety-six good outcome patients with chronic post-aSAH fatigue answered the questionnaires Brief COPE, (a questionnaire defining 14 coping strategies and three Coping Styles), the Fatigue Severity Scale (FSS), Mental Fatigue Scale (MFS), Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory (BAI). The Brief COPE scores were compared with fatigue severity and emotional symptoms of the patients. RESULTS: The prevailing coping strategies were "Acceptance", "Emotional Support", "Active Coping" and "Planning". "Acceptance" was the sole coping strategy that was significantly inversely related to levels of fatigue. Patients with the highest scores for mental fatigue and those with clinically significant emotional symptoms applied significantly more maladaptive avoidant strategies. Females and the youngest patients applied more "Problem-Focused" strategies. CONCLUSION: A therapeutic behavioural model aiming at furthering "Acceptance" and reducing passivity and "Avoidant" strategies may contribute to alleviate post-aSAH fatigue in good outcome patients. Given the chronic nature of post-aSAH fatigue, neurosurgeons may encourage patients to accept their new situation so that they can start a process of positive reframing instead of being trapped in a spiral of futile loss of energy and secondary increased emotional burden and frustration.

Two symptoms can accurately identify post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND: Post-exertional malaise (PEM) is the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) yet its diverse manifestations make it difficult to recognize. Brief instruments for detecting PEM are critical for clinical and scientific progress. OBJECTIVE: To develop a clinical prediction rule for PEM. METHOD: 49 ME/CFS and 10 healthy, sedentary subjects recruited from the community completed two maximal cardiopulmonary exercise tests (CPETs) separated by 24 hours. At five different times, subjects reported symptoms which were then classified into 19 categories. The frequency of symptom reports between groups at each time point was compared using Fisher's exact test. Receiver operating characteristics (ROC) analysis with area under the curve calculation was used to determine the number of different types of symptom reports that were sufficient to differentiate between ME/CFS and sedentary groups. The optimal number of symptoms was determined where sensitivity and specificity of the types of symptom reports were balanced. RESULTS: At all timepoints, a maximum of two symptoms was optimal to determine differences between groups. Only one symptom was necessary to optimally differentiate between groups at one week following the second CPET. Fatigue, cognitive dysfunction, lack of positive feelings/mood and decrease in function were consistent predictors of ME/CFS group membership across timepoints. CONCLUSION: Inquiring about post-exertional cognitive dysfunction, decline in function, and lack of positive feelings/mood may help identify PEM quickly and accurately. These findings should be validated with a larger sample of patients.

Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan.

OBJECTIVE: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan. METHODS: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls. RESULTS: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04-1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59-2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09-1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women. CONCLUSION: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.

Role of selective attention in fatigue in neurological disorders.

BACKGROUND: Chronic fatigue is a significant symptom in several diseases including traumatic and degenerative neurological disorders. While several studies have investigated the correlates of chronic fatigue, there is as yet no unifying framework to explain chronic fatigue. METHODS: In this narrative review, I investigate the role of selective attention in the development of chronic fatigue and discuss results within the framework of the sensory attenuation model of fatigue, which posits that fatigue is the phenomenological output of altered attention to sensory input. Following a short introduction of this framework, I present results from investigations that address attentional mechanisms in fatigue in multiple sclerosis, stroke, traumatic brain injury and Parkinson's disease. RESULTS: Attention was quantified in all four disease models using a variety of outcome measures, including behavioural, neurophysiological, structural and functional brain connectivity. The range of measures precluded direct comparison of results across disease conditions; however, in all four disease models there was evidence of poor selective attention that explained levels of chronic fatigue, supporting the sensory attenuation model of fatigue as a disease-independent mechanism of fatigue. Evidence was lacking to draw any conclusions about the direction of causality. CONCLUSION: The role of selective attention in development of fatigue is indicated. Future studies must focus on establishing causality and exploring attentional circuitry as a potential therapeutic target.

A Causal-Pathway Phenotype of Chronic Fatigue Syndrome due to Hemodialysis in Patients with End-Stage Renal Disease.

BACKGROUND: End-stage renal disease (ESRD) is associated with fatigue and physiosomatic symptoms. OBJECTIVE: The objective of this study is to delineate the associations between severity of fatigue and physio-somatic symptoms and glomerular filtration rate, inflammatory biomarkers, and Wnt/cateninpathway proteins. METHODS: The Wnt-pathway related proteins ß-catenin, Dickkopf-related protein 1 (DKK1), R-spondin- 1, and sclerostin were measured by ELISA technique in 60 ESRD patients and 30 controls. The Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to assess the severity of FF symptoms. RESULTS: ESRD is characterized by a significant increase in the total FF score, muscle tension, fatigue, sadness, sleep disorders, gastro-intestinal (GI) symptoms, and a flu-like malaise. The total-FF score was significantly correlated with serum levels of urea, creatinine, and copper (positively), and ß-catenin, eGFR, hemoglobin, albumin, and zinc (inversely). The total-FF score was associated with the number of total dialysis and weekly dialysis sessions, and these dialysis characteristics were more important in predicting FF scores than eGFR measurements. Partial Least Squares analysis showed that the FF score comprised two factors that are differently associated with biomarkers: a) 43.0% of the variance in fatigue, GI symptoms, muscle tension, sadness, and insomnia is explained by hemoglobin, albumin, zinc, ß-catenin, and R-spondin-1; and b) 22.3% of the variance in irritability, concentration and memory impairments by increased copper and cations/chloride ratio, and male sex. CONCLUSION: ESRD patients show high levels of fatigue and physio-somatic symptoms associated with hemodialysis and mediated by dialysis-induced changes in inflammatory pathways, the Wnt/catenin pathway, and copper.

Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? OBJECTIVE: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. METHODS: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. RESULTS: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. CONCLUSIONS: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Subjective and objective cognitive function in adolescent with chronic fatigue following Epstein-Barr virus infection.

OBJECTIVE: Cognitive difficulties are among the most disruptive and disabling problems reported by chronic fatigue syndrome (CFS) sufferers. Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and CFS. The aim of this study was to investigate subjectively reported and objectively measured cognitive functioning in fatigued and non-fatigued adolescents six months after EBV infection. METHODS: A total of 195 adolescents (12-19 years) with acute EBV infection were followed prospectively for six months, after which they were grouped as chronically fatigued (CF+) and non-fatigued (CF-) cases based on questionnaire score; the CF+-group was further subgrouped according to CFS diagnosis. A group of 70 healthy controls was also included. Groups were cross-sectionally compared on objective measures of processing speed, executive functions and memory, and subjective cognitive functioning. RESULTS: There were no group differences regarding objective cognitive measures, but the CF+-group reported significantly (p < 0.001) more cognitive problems (cognitive symptoms sum score = 9.5) compared to the CF--group (cognitive symptoms sum score = 5.3) and the healthy control group (cognitive symptoms sum score = 6.4). The CFS subgroup rated symptoms scores even higher but did not differ on cognitive performance tests. CONCLUSION: Subjective experiences of cognitive difficulties characterize adolescents with CF and CFS six months after acute EBV infection, whereas objective measures of cognitive impairment are inconspicuous.

Long-term sequelae of COVID-19 (myalgic encephalomyelitis): An international cross-sectional study.

BACKGROUND: As a result of prolonged effects on multiple organs, recovery from COVID-19 caused by SARS-CoV-2 cannot be verified. This study seeks to understand chronic and acute long-term symptoms of COVID-19 lasting from a few weeks after diagnosis. The study also aims to gain insight into prevalence of chronic fatigue syndrome/myalgic encephalomyelitis, a potentially comorbid condition for several months after the infection, in addition to taking a broad perspective on rare symptoms that may have developed during or after the infection. STUDY DESIGN: Cross-sectional questionnaire\descriptive study. METHODS: The questionnaire was developed to assess the long-term effects of the global pandemic of COVID-19 using DePaul Symptom Questionnaire-2. The DePaul Symptom Questionnaire, Patient Health Questionnaire, and other symptoms that have been introduced by literature review. DISCUSSION: A large cohort of people from all over the world will be examined to understand the differential effects of people who have experienced COVID-19, as well as the potential occurrence of ME. In total, 20,000 COVID patients are expected to be included in the study by Sep 1, 2022. Patients who have experienced COVID-19 will be asked about their persistent symptoms from 1 week up to more than 6 months after catching or recovery from the infection.

Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes.

COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as "long-COVID" or "post-COVID-19" syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge. A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms. Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories. Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.