RESUMO
BACKGROUND: Post COVID-19 condition (PCC) is a complication of SARS-COV-2 infection and can lead to long-term disability. METHODS: The present study was designed to analyse the gene expression patterns of PCC through bulk RNA sequencing of whole blood and to explore the potential molecular mechanisms of PCC. Whole blood was collected from 80 participants enrolled in a prospective cohort study following SARS-CoV-2 infected and non-infected individuals for 6 months after recruitment and was used for bulk RNA sequencing. Identification of differentially expressed genes (DEG), pathway enrichment and immune cell deconvolution was performed to explore potential biological pathways involved in PCC. RESULTS: We have found 13 differentially expressed genes associated with PCC. Enriched pathways were related to interferon-signalling and anti-viral immune processes. CONCLUSION: The PCC transcriptome is characterized by a modest overexpression of interferon-stimulated genes, pointing to a subtle ongoing inflammatory response.
Assuntos
COVID-19 , Humanos , Adolescente , Adulto Jovem , SARS-CoV-2 , Estudos Prospectivos , Síndrome de COVID-19 Pós-Aguda , Análise de Sequência de RNA , Doença Crônica , InterferonsRESUMO
BACKGROUND: Long-term stress causing altered hypothalamic-pituitary-adrenal (HPA) axis dynamics with cortisol dysfunction may be involved in the pathophysiology of functional somatic disorders (FSD), but studies on adolescents with multi-system FSD are lacking. Therefore, we investigated: 1) whether hair cortisol concentration (HCC) differentiates adolescents with multi-system FSD from a) a population-based sample and b) a subgroup derived from the sample reporting a high physical symptom load, and 2) whether FSD population HCC is associated with primary symptom presentations and self-perceived stress. METHODS: We used data from a clinical sample with multi-system FSD (N = 91, age 15-19 years) and a population-based sample (N = 1,450, age 16-17 years) including a subgroup with top 10% total scores on physical symptoms (N = 147). Density plots and multiple linear regression were applied to compare HCC between groups. In the clinical sample, multiple linear regression was employed to assess the association between HCC and primary symptom clusters and self-perceived stress. RESULTS: Median HCC was lower in the clinical sample than in the population-based sample (ß = 0.80 (95%CI: 0.66, 0.97)), but not significantly different from median HCC in the derived subgroup (ß = 0.84 (95%CI: 0.66, 1.07)). In the clinical sample, HCC was not significantly associated with primary symptom clusters (F(2, 82) = 0.13, p = 0.88) or self-perceived stress (F(4, 83) = 1.18, p = 0.33). CONCLUSION: Our findings indicate that HCC is lowered in adolescents with multi-system FSD but not significantly associated with primary symptom presentations or self-perceived stress. Future studies including multiple measures of HPA axis dynamics alongside psychological measures may further elucidate the role of long-term stress in FSD. TRIAL REGISTRATION: The AHEAD study was pre-registered at ClinicalTrials.gov (NCT02346071), 26/01/2015.
Assuntos
Hidrocortisona , Sistema Hipotálamo-Hipofisário , Humanos , Adolescente , Adulto Jovem , Adulto , Síndrome , Sistema Hipófise-Suprarrenal , Estresse Psicológico/psicologia , CabeloRESUMO
BACKGROUND: Chronic fatigue syndrome (CFS) is defined according to subjective symptoms only, and several conflicting case definition exist. Previous research has discovered certain biological alterations. The aim of the present study was to explore possible subgroups based on biological markers within a widely defined cohort of adolescent CFS patients and investigate to what extent eventual subgroups are associated with other variables. METHODS: The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) has previously performed detailed investigation of immunological, autonomic, neuroendocrine, cognitive and sensory processing functions in an adolescent group of CFS patients recruited according to wide diagnostic criteria. In the present study, hierarchical cluster analyses (Ward's method) were performed using representative variables from all these domains. Associations between clusters and constitutional factors (including candidate genetic markers), diagnostic criteria, subjective symptoms and prognosis were explored by standard statistical methods. RESULTS: A total of 116 patients (26.7% males, mean age 15.4 years) were included. The final cluster analyses revealed six clusters labelled pain tolerant & good cognitions, restored HPA dynamics, orthostatic intolerance, low-grade inflammation, pain intolerant & poor cognitions, and high vagal (parasympathetic) activity, respectively. There was substantial overlap between clusters. The pain intolerant & poor cognitions-cluster was associated with low functional abilities and quality of life, and adherence to the Canada 2003 diagnostic criteria for CFS. No other statistically significant cluster associations were discovered. CONCLUSION: Within a widely defined cohort of adolescent CFS patients, clusters could be delineated, but no distinct subgroups could be identified. Associations between clusters and constitutional factors, subjective symptoms and prognosis were scarce. These results question the clinical usefulness of searching for CFS subgroups, as well as the validity of the most "narrow" CFS diagnostic criteria. TRIAL REGISTRATION: Clinical Trials NCT01040429.
Assuntos
Síndrome de Fadiga Crônica , Adolescente , Biomarcadores , Canadá , Análise por Conglomerados , Feminino , Humanos , Masculino , Noruega , Qualidade de VidaRESUMO
PURPOSE: Heart transplantation (HTx) implies denervation of afferent neural connections. Reinnervation of low-pressure cardiopulmonary baroreceptors might impact the development and treatment of hypertension, but little is known of its occurrence. The present prospective study investigated possible afferent reinnervation of low-pressure cardiopulmonary baroreceptors during the first year after heart transplantation. METHODS: A total of 50 heart transplant recipients (HTxRs) were included and were evaluated 7-12 weeks after transplant surgery, with follow-up 6 and 12 months later. In addition, a reference group of 50 healthy control subjects was examined once. Continuous, non-invasive recordings of cardiovascular variables were carried out at supine rest, during 15 min of 20° head-up tilt, during Valsalva maneuver and during 1 min of 30% maximal voluntary handgrip. In addition, routine clinical data including invasive measurements were used in the analyses. RESULTS: During the first year after HTx, the heart rate (HR) response to 20° head-up tilt partly normalized, a negative relationship between resting mean right atrial pressure and HR tilt response developed, low-frequency variability of the RR interval and systolic blood pressure at supine rest increased, and the total peripheral resistance response to Valsalva maneuver became stronger. CONCLUSION: Functional assessments suggest that afferent reinnervation of low-pressure cardiopulmonary receptors occurs during the first year after heart transplantation, partially restoring reflex-mediated responses to altered cardiac filling.
Assuntos
Sistema Cardiovascular/inervação , Força da Mão/fisiologia , Frequência Cardíaca/fisiologia , Transplante de Coração , Pulmão/inervação , Pressorreceptores/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
INTRODUCTION: Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue and Chronic Fatigue Syndrome (CFS). This study investigated baseline predictors of chronic fatigue six months after an acute EBV infection. MATERIALS AND METHODS: A total of 200 adolescents (12-20â¯years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. We performed linear regression to assess possible associations between baseline predictors and fatigue (Chalder Fatigue Questionnaire total score) six months after the acute EBV infection. A total of 70 healthy controls were included for cross-sectional reference. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). RESULTS: In the final multiple linear regression model, fatigue six months after acute EBV infection was significantly and independently predicted by the following baseline variables (regression coefficient B[95% CI]): Sensory sensitivity (0.8[0.09-1.6]), pain severity (0.2[0.02-0.3]), functional impairment (1000â¯steps/day) (-0.3[-0.5 to -0.08]), negative emotions (anxiety) (0.4[0.2-0.6]), verbal memory (correct word recognition) (1.7[0.1-3.3]), plasma C-reactive protein (2.8[1.1-4.4] for CRP values >0.86) and plasma Vitamin B12 (-0.005[-0.01 to -0.001]). CONCLUSIONS: Development of fatigue after acute EBV infection is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes. TRIAL REGISTRATION: ClinicalTrials, ID: NCT02335437, https://clinicaltrials.gov/ct2/show/NCT02335437.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Síndrome de Fadiga Crônica/etiologia , Adolescente , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Criança , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Infecções por Vírus Epstein-Barr/imunologia , Fadiga , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/fisiopatologia , Feminino , Previsões/métodos , Herpesvirus Humano 4/patogenicidade , Humanos , Mononucleose Infecciosa , Modelos Lineares , Masculino , Estudos Prospectivos , Adulto JovemRESUMO
INTRODUCTION: Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and Chronic Fatigue Syndrome (CFS). The aim of this cross-sectional study was to explore clinical symptoms as well as markers of disease mechanisms in fatigued and non-fatigued adolescents 6â¯months after EBV-infection, and in healthy controls. MATERIALS AND METHODS: A total of 200 adolescents (12-20â¯years old) with acute EBV infection were assessed 6â¯months after the initial infectious event and divided into fatigued (EBV CF+) and non-fatigued (EBV CF-) cases based on questionnaire score. The EBV CF+ cases were further sub-divided according to case definitions of CFS. In addition, a group of 70 healthy controls with similar distribution of sex and age was included. Symptoms were mapped with a questionnaire. Laboratory assays included EBV PCR and serology; detailed blood leukocyte phenotyping and serum high-sensitive C-reactive protein; and plasma and urine cortisol and catecholamines. Assessment of autonomic activity was performed with continuous, non-invasive monitoring of cardiovascular variables during supine rest, controlled breathing and upright standing. Differences between EBV CF+ and EBV CF- were assessed by simple and multiple linear regression adjusting for sex as well as symptoms of depression and anxiety. A p-valueâ¯≤â¯0.05 was considered statistically significant. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). RESULTS: The EBV CF+ group had significantly higher scores for all clinical symptoms. All markers of infection and most immune, neuroendocrine and autonomic markers were similar across the EBV CF+ and EBV CF- group. However, the EBV CF+ group had slightly higher serum C-reactive protein (0.48 vs 0.43â¯mg/L, pâ¯=â¯0.031, high-sensitive assay), total T cell (CD3+) count (median 1573 vs 1481â¯×â¯106 cells/L, pâ¯=â¯0.012), plasma norepinephrine (1420 vs 1113â¯pmol/L, pâ¯=â¯0.01) and plasma epinephrine (363 vs 237â¯nmol/L, pâ¯=â¯0.032); lower low-frequency:high frequency (LF/HF) ratio of heart rate variability at supine rest (0.63 vs 0.76, pâ¯=â¯0.008); and an attenuated decline in LF/HF ratio during controlled breathing (-0.11 vs -0.25, pâ¯=â¯0.002). Subgrouping according to different CFS diagnostic criteria did not significantly alter the results. Within the EBV CF+ group, there were no strong correlations between clinical symptoms and markers of disease mechanisms. In a multiple regression analysis, serum CRP levels were independently associated with serum cortisol (Bâ¯=â¯4.5â¯×â¯10-4, pâ¯<â¯0.001), urine norepinephrine (Bâ¯=â¯9.6â¯×â¯10-2, pâ¯=â¯0.044) and high-frequency power of heart rate variability (Bâ¯=â¯-3.7â¯×â¯10-2, pâ¯=â¯0.024). CONCLUSIONS: In adolescents, CF and CFS 6â¯months after acute EBV infection are associated with high symptom burden, but no signs of increased viral load and only subtle alterations of immune, autonomic, and neuroendocrine markers of which no one is strongly correlated with symptom scores. A slight sympathetic over parasympathetic predominance is evident in CF and might explain slightly increased CRP levels.
Assuntos
Infecções por Vírus Epstein-Barr/fisiopatologia , Síndrome de Fadiga Crônica/metabolismo , Síndrome de Fadiga Crônica/fisiopatologia , Adolescente , Sistema Nervoso Autônomo/metabolismo , Biomarcadores/sangue , Proteína C-Reativa/análise , Sistema Cardiovascular/metabolismo , Estudos de Casos e Controles , Catecolaminas/análise , Catecolaminas/sangue , Catecolaminas/urina , Estudos Transversais , Epinefrina/metabolismo , Infecções por Vírus Epstein-Barr/metabolismo , Fadiga/metabolismo , Fadiga/fisiopatologia , Síndrome de Fadiga Crônica/sangue , Feminino , Frequência Cardíaca/fisiologia , Herpesvirus Humano 4/metabolismo , Herpesvirus Humano 4/patogenicidade , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Hidrocortisona/urina , Leucócitos/citologia , Masculino , Sistemas Neurossecretores/metabolismo , Norepinefrina/metabolismo , Projetos Piloto , Adulto JovemRESUMO
OBJECTIVES: The aim of this double-blinded randomised placebo-controlled trial was to investigate the efficacy of clonidine for delirium in medical inpatients greater than 65 years. METHODS: Acutely admitted medical patients greater than 65 years with delirium or subsyndromal delirium were eligible for inclusion. Included patients were given a loading dose of either placebo or clonidine; 75 µg every third hour up to a maximum of four doses to reach steady state and further 75 µg twice daily until delirium free for 2 days, discharge or a maximum of 7 days of treatment. The primary endpoint was the trajectory of the Memorial Delirium Assessment Scale (MDAS) for the 7 days of treatment. Presence of delirium according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria and severity measured by MDAS were assessed daily until discharge or a maximum of 7 days after end of treatment. RESULTS: Because of slower enrolment than anticipated, the study was halted early. Ten patients in each group were studied. The low recruitment rate was mainly due to the presence of multiple patient exclusion criteria for patient safety. There was no significant difference between the treatment group in the primary endpoint comparing the trajectory of MDAS for the 7 days of treatment using mixed linear models with log transformation, (P = .60). The treatment group did not have increased adverse effects. CONCLUSIONS: No effect of clonidine for delirium was found, although the study was under powered. Further studies in less frail populations are now required.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Clonidina/uso terapêutico , Delírio/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Delírio/etiologia , Método Duplo-Cego , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Alterations in autonomic nervous system (ANS) activity might be involved in the pathophysiology of delirium. The aim was to explore autonomic cardiovascular control in older patients with and without delirium. METHODS: Fourteen patients (five with delirium) acutely admitted to the geriatric ward with an infection were enrolled in the study. Patients with atrial fibrillation, a pacemaker, or on treatment with beta-blockers, calcium channel blockers or acetylcholinesterase inhibitors were not eligible. Continuous, non-invasive hemodynamic variables were measured during supine rest (5 min) and head-up tilt (HUT) to 15 degrees (10 min). Heart rate (HR), blood pressure (BP) and stroke volume (SV) were recorded beat-to-beat. Cardiac output (CO), total peripheral resistance (TPR), end-diastolic volume (EDV) and heart rate variability (HRV) values were calculated. RESULTS: Median age was 86 years. HR, BP, SV, CO, TPR and EDV were similar across the two groups at rest, but there was a trend towards a greater increase in systolic BP and HR during HUT in the delirium group. At rest, all HRV indices were higher in the delirium group, but the differences were not statistically significant. During HUT, the delirium group had higher power spectral density (PSD) (representing total variability) (p = 0.06) and a lower low frequency (LF)/high frequency (HF)-ratio (an index of sympathovagal balance) than the control group (p = 0.06). Also, delirious patients had a significantly greater reduction in standard deviation of RR-intervals (SDNN) (representing total variability) from baseline than controls (p = 0.01) during HUT. CONCLUSIONS: This explorative pilot study on autonomic cardiovascular control in delirium suggests that there may be differences in HRV that should be further investigated in larger samples.
Assuntos
Pressão Sanguínea/fisiologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/fisiopatologia , Delírio/epidemiologia , Delírio/fisiopatologia , Frequência Cardíaca/fisiologia , Idoso , Idoso de 80 Anos ou mais , Sistema Nervoso Autônomo/fisiologia , Feminino , Humanos , Masculino , Noruega/epidemiologia , Projetos Piloto , Posição Ortostática , Teste da Mesa Inclinada/métodosRESUMO
PURPOSE: Heart transplantation causes denervation of the donor heart, but the consequences for cardiovascular homeostasis remain to be fully understood. The present study investigated cardiovascular autonomic control at supine rest, during orthostatic challenge and during isometric exercise in heart transplant recipients (HTxR). METHODS: A total of 50 HTxRs were investigated 7-12 weeks after transplant surgery and compared with 50 healthy control subjects. Continuous, noninvasive recordings of cardiovascular variables were carried out at supine rest, during 15 min of 60° head-up tilt and during 1 min of 30% of maximal voluntary handgrip. Plasma and urine catecholamines were assayed, and symptoms were charted. RESULTS: At supine rest, heart rate, blood pressures and total peripheral resistance were higher, and stroke volume and end diastolic volume were lower in the HTxR group. During tilt, heart rate, blood pressures and total peripheral resistance increased less, and stroke volume and end diastolic volume decreased less. During handgrip, heart rate and cardiac output increased less, and stroke volume and end diastolic volume decreased less. Orthostatic symptoms were similar across the groups, but the HTxRs complained more of pale and cold hands. CONCLUSION: HTxRs are characterized by elevated blood pressures and total peripheral resistance at supine rest as well as attenuated blood pressures and total peripheral resistance responses during orthostatic challenge, possibly caused by low-pressure cardiopulmonary baroreceptor denervation. In addition, HTxRs show attenuated cardiac output response during isometric exercise due to efferent sympathetic denervation. These physiological limitations might have negative functional consequences.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Exercício Físico , Transplante de Coração/efeitos adversos , Intolerância Ortostática/epidemiologia , Transplantados , Adolescente , Adulto , Idoso , Pressão Sanguínea , Catecolaminas/sangue , Catecolaminas/urina , Feminino , Força da Mão , Coração/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Intolerância Ortostática/fisiopatologiaRESUMO
AIM: Acute Epstein-Barr virus (EBV) infection is a trigger of prolonged fatigue. This study investigated baseline predictors of physical activity six months after an acute EBV infection. METHODS: A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. In this exploratory study, we performed linear regression analysis to assess possible associations between baseline predictors and steps per day at six months. RESULTS: In the final multiple linear regression model, physical activity six months after acute EBV infection was significantly and independently predicted by baseline physical activity (steps per day), substance use (alcohol and illicit drugs) and human growth hormone (adjusted R2 = 0.20). CONCLUSION: Baseline physical activity, substance use and plasma growth hormone are independent predictors of physical activity six months after an acute EBV infection in adolescents, whereas markers of the infection and associated immune response do not seem to be associated with physical activity six months later.
Assuntos
Infecções por Vírus Epstein-Barr/reabilitação , Exercício Físico , Adolescente , Consumo de Bebidas Alcoólicas , Estudos Transversais , Infecções por Vírus Epstein-Barr/sangue , Feminino , Hormônio do Crescimento/sangue , Humanos , Estilo de Vida , Masculino , Estudos ProspectivosAssuntos
Síndrome de Fadiga Crônica , Adolescente , Biomarcadores , Estudos Transversais , Fadiga , Herpesvirus Humano 4 , HumanosRESUMO
Introduction: The post-COVID-19 condition (PCC) is characterized by debilitating persistent symptoms, including symptoms suggesting neurological aberrations such as concentration difficulties, impaired memory, pain, and sleep disturbances. The underlying mechanisms remain elusive. This study aimed to investigate brain injury biomarkers, neurocognitive test performance, and self-reported neurological and neuropsychological symptoms in young people with PCC. Methods: A total of 404 non-hospitalized adolescents and young adults aged 12-25 years who tested positive for SARS-CoV-2, along with 105 matched SARS-CoV-2 negative individuals, were prospectively enrolled and followed-up for 6 months (Clinical Trials ID: NCT04686734). All participants underwent comprehensive assessment encompassing clinical examinations, questionnaires, neurocognitive testing and blood sampling. Serum samples were immunoassayed for the brain injury biomarkers neurofilament light chain (Nfl) and glial fibrillary acidic protein (GFAp). At 6 months, cross-sectional analyses of serum Nfl/GFAp, neurocognitive test results and symptom scores were performed across groups based on adherence to PCC criteria as well as initial SARS-CoV-2 test results. Also, associations between Nfl/GFAp, neurocognitive test results, and symptom scores were explored. Results: A total of 381 SARS-CoV-2 positive and 85 SARS-CoV-2 negative were included in the final analysis at 6 months, of whom 48% and 47%, respectively, adhered to the PCC criteria. Serum levels of Nfl and GFAp were almost equal across groups and did not differ from reference values in healthy populations. Also, neurocognitive test results were not different across groups, whereas symptom scores were significantly higher in patients fulfilling PCC criteria (independent of initial SARS-CoV-2 status). No significant associations between Nfl/GFAp, neurocognitive test results, and symptom scores were found. Conclusion: Normal brain injury biomarkers and neurocognitive performance 6 months after mild COVID-19 implies that the persistent symptoms associated with PCC are not concurrent with ongoing central nervous system damage or permanent disruption of cognitive functions. This finding contradicts the notion of neuroinflammation as a likely explanation for the persistent symptoms.
RESUMO
Importance: The prevalence and baseline risk factors of post-COVID-19 condition (PCC) remain unresolved among the large number of young people who experienced mild COVID-19. Objectives: To determine the point prevalence of PCC 6 months after the acute infection, to determine the risk of development of PCC adjusted for possible confounders, and to explore a broad range of potential risk factors. Design, Setting, and Participants: This cohort study included nonhospitalized individuals from 2 counties in Norway between ages 12 and 25 years who underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. At the early convalescent stage and at 6-month follow-up, participants underwent a clinical examination; pulmonary, cardiac, and cognitive functional testing; immunological and organ injury biomarker analyses; and completion of a questionnaire. Participants were classified according to the World Health Organization case definition of PCC at follow-up. Association analyses of 78 potential risk factors were performed. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The point prevalence of PCC 6 months after RT-PCR testing in the SARS-CoV-2-positive and SARS-CoV-2-negative groups, and the risk difference with corresponding 95% CIs. Results: A total of 404 individuals testing positive for SARS-CoV-2 and 105 individuals testing negative were enrolled (194 male [38.1%]; 102 non-European [20.0%] ethnicity). A total of 22 of the SARS-CoV-2-positive and 4 of the SARS-CoV-2-negative individuals were lost to follow-up, and 16 SARS-CoV-2-negative individuals were excluded due to SARS-CoV-2 infection in the observational period. Hence, 382 SARS-CoV-2-positive participants (mean [SD] age, 18.0 [3.7] years; 152 male [39.8%]) and 85 SARS-CoV-2-negative participants (mean [SD] age, 17.7 [3.2] years; 31 male [36.5%]) could be evaluated. The point prevalence of PCC at 6 months was 48.5% in the SARS-CoV-2-positive group and 47.1% in the control group (risk difference, 1.5%; 95% CI, -10.2% to 13.1%). SARS-CoV-2 positivity was not associated with the development of PCC (relative risk [RR], 1.06; 95% CI, 0.83 to 1.37; final multivariable model utilizing modified Poisson regression). The main risk factor for PCC was symptom severity at baseline (RR, 1.41; 95% CI, 1.27-1.56). Low physical activity (RR, 0.96; 95% CI, 0.92-1.00) and loneliness (RR, 1.01; 95% CI, 1.00-1.02) were also associated, while biological markers were not. Symptom severity correlated with personality traits. Conclusions and Relevance: The persistent symptoms and disability that characterize PCC are associated with factors other than SARS-CoV-2 infection, including psychosocial factors. This finding raises questions about the utility of the World Health Organization case definition and has implications for the planning of health care services as well as for further research on PCC.
Assuntos
COVID-19 , Humanos , Masculino , Adulto Jovem , Adolescente , Criança , Adulto , COVID-19/epidemiologia , SARS-CoV-2 , Prevalência , Estudos de Coortes , Fatores de RiscoRESUMO
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.
Assuntos
Infecções por Vírus Epstein-Barr , Síndrome de Fadiga Crônica , Adolescente , Humanos , Infecções por Vírus Epstein-Barr/complicações , Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/diagnóstico , Herpesvirus Humano 4 , CogniçãoRESUMO
Introduction: Both public and scientific attention have shifted from the acute COVID-19 illness to the chronic disability experienced by a proportion of COVID-19 convalescents. Post COVID-19 condition, a term used for long-lasting symptoms after COVID-19, can affect individuals across all disease severity and age groups. Data on post-COVID-19 symptomatology, epidemiology and pathophysiology in adolescents and young adults are scarce. To date, little is known on the immunological and pulmonary trends in these patients after COVID-19. This study investigated immunological markers and pulmonary function in non-hospitalized patients in this group at 6 months after initial mild COVID-19 infection. Methods: Non-hospitalized SARS-CoV-2 positive (n = 405) and SARS-CoV-2 negative (n = 111) adolescents and young adults (aged 12-25 years) were followed prospectively for six months after SARS-CoV-2 PCR testing. At baseline and at six months follow-up, all participants underwent an assessment including clinical examination, questionnaires, spirometry, and blood sampling. Cross-sectional comparisons of blood biomarkers; including white blood cell counts, CRP, GDF-15, a 27-multiplex cytokine assay, complement activation products and SARS-CoV-2 antibodies; and spirometry measures were performed after classification of all participants according to their COVID-19 status and adherence to post-COVID-19 case criteria. Associations between biomarkers and COVID-19 symptoms were explored. Results: No difference in pulmonary function was detected between the groups. COVID-19 convalescents had higher levels of chemokines eotaxin, MCP-1 and IP-10 than non-infected controls. The increase was modest and not associated with long-lasting COVID-19 symptoms. Discussion: Elevated inflammatory mediators were found in adolescents and young adults six months after mild COVID-19, but there was no association with post-COVID-19 condition.
Assuntos
COVID-19 , Humanos , Adolescente , Adulto Jovem , SARS-CoV-2 , Estudos Transversais , Gravidade do Paciente , BiomarcadoresRESUMO
Introduction: Coronavirus disease 2019 (COVID-19) is prevalent among young people, and neurological involvement has been reported. We investigated neurological symptoms, cognitive test results, and biomarkers of brain injury, as well as associations between these variables in non-hospitalized adolescents and young adults with COVID-19. Methods: This study reports baseline findings from an ongoing observational cohort study of COVID-19 cases and non-COVID controls aged 12-25 years (Clinical Trials ID: NCT04686734). Symptoms were charted using a standardized questionnaire. Cognitive performance was evaluated by applying tests of working memory, verbal learning, delayed recall, and recognition. The brain injury biomarkers, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp), were assayed in serum samples using ultrasensitive immunoassays. Results: A total of 405 COVID-19 cases and 111 non-COVID cases were prospectively included. Serum Nfl and GFAp concentrations were significantly elevated in COVID-19 cases as compared with non-COVID controls (p = 0.050 and p = 0.014, respectively). The COVID-19 cases reported more fatigue (p < 0.001) and post-exertional malaise (PEM) (p = 0.001) compared to non-COVID-19 controls. Cognitive test performance and clinical neurological examination did not differ across the two groups. Within the COVID-19 group, there were no associations between symptoms, cognitive test results, and NfL or GFAp levels. However, fatigue and PEM were strongly associated with older age and female sex. Conclusions: Non-hospitalized adolescents and young adults with COVID-19 reported more fatigue and PEM and had slightly elevated levels of brain injury markers, but showed normal cognitive performance. No associations were found between symptoms, brain injury markers, and cognitive test results, but fatigue and PEM were strongly related to female sex and older age.
RESUMO
Summary: Mild, subacute COVID-19 in young people show inflammatory enhancement, but normal pulmonary function. Inflammatory markers are associated with age and male sex, whereas clinical symptoms are associated with age and female sex, but not with objective disease markers. Background: Coronavirus Disease 2019 (COVID-19) is widespread among adolescents and young adults across the globe. The present study aimed to compare inflammatory markers, pulmonary function and clinical symptoms across non-hospitalized, 12 - 25 years old COVID-19 cases and non-COVID-19 controls, and to investigate associations between inflammatory markers, clinical symptoms, pulmonary function and background variables in the COVID-19 group. Methods: The present paper presents baseline data from an ongoing longitudinal observational cohort study (Long-Term Effects of COVID-19 in Adolescents, LoTECA, ClinicalTrials ID: NCT04686734). A total of 31 plasma cytokines and complement activation products were assayed by multiplex and ELISA methodologies. Pulmonary function and clinical symptoms were investigated by spirometry and questionnaires, respectively. Results: A total of 405 COVID-19 cases and 111 non-COVID-19 controls were included. The COVID-19 group had significantly higher plasma levels of IL-1ß, IL-4, IL-7, IL-8, IL-12, TNF, IP-10, eotaxin, GM-CSF, bFGF, complement TCC and C3bc, and significantly lower levels of IL-13 and MIP-1α, as compared to controls. Spirometry did not detect any significant differences across the groups. IL-4, IL-7, TNF and eotaxin were negatively associated with female sex; eotaxin and IL-4 were positively associated with age. Clinical symptoms were positively associated with female sex and age, but not with objective disease markers. Conclusions: Among non-hospitalized adolescents and young adults with COVID-19 there was significant alterations of plasma inflammatory markers in the subacute stage of the infection. Still, pulmonary function was normal. Clinical symptoms were independent of inflammatory and pulmonary function markers, but positively associated with age and female sex.
Assuntos
COVID-19/imunologia , Pulmão/metabolismo , Pulmão/patologia , SARS-CoV-2/fisiologia , Doença Aguda , Adolescente , Adulto , Biomarcadores/metabolismo , Criança , Feminino , Hospitalização , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Testes de Função Respiratória , Adulto JovemRESUMO
Background: Epstein-Barr virus (EBV) causes infectious mononucleosis (IM) that can lead to chronic fatigue syndrome. The CEBA-project (Chronic fatigue following acute EBV infection in Adolescents) has followed 200 patients with IM and here we present an immunological profiling of adolescents with IM related to clinical characteristics. Methods: Patients were sampled within 6 weeks of debut of symptoms and after 6 months. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated in vitro (n=68), and supernatants analyzed for cytokine release. Plasma was analyzed for inflammatory markers (n=200). The Chalder Fatigue Questionnaire diagnosed patients with and without chronic fatigue at 6 months (CF+ and CF- group, respectively) (n=32 and n=91, in vitro and plasma cohorts, respectively. Results: Broad activation of PBMC at baseline, with high levels of RANTES (Regulated on activation, normal T-cell expressed and secreted) in the CF+ group, and broad inflammatory response in plasma with high levels of T-cell markers was obeserved. At 6 months, there was an increased ß-agonist response and RANTES was still elevated in cultures from the CF+ group. Plasma showed decrease of inflammatory markers except for CRP which was consistently elevated in the CF+ group. Conclusion: Patients developing chronic fatigue after IM have signs of T-cell activation and low-grade chronic inflammation at baseline and after 6 months. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02335437.