Search Results (880)

Background: Post-COVID syndrome represents a significant medical and public health challenge, particularly among older adults and individuals with type 2 diabetes mellitus (T2DM), in whom disturbances in immune and metabolic homeostasis may contribute to the development and persistence of symptoms following SARS-CoV-2 infection. Objective: To investigate the clinical, immunological, and metabolic characteristics of post-COVID syndrome in older adults with T2DM. Methods: A cross-sectional comparative study was conducted involving 141 patients aged ≥ 60 years who were evaluated more than one year after SARS-CoV-2 infection. Clinical data, anthropometric measurements, complete blood count parameters, biochemical markers, glycated hemoglobin (HbA1c), and SARS-CoV-2-specific IgG antibodies were assessed. Statistical analyses were performed using nonparametric methods, while Pearson’s χ² test was applied for categorical variables. A p-value < 0.05 was considered statistically significant. Results: Symptoms consistent with post-COVID syndrome one year after SARS-CoV-2 infection were identified in 53.2% of participants. No significant differences in anthropometric characteristics, hematological parameters, or most biochemical markers were observed between patients with and without post-COVID syndrome. Patients with T2DM exhibited higher fasting glucose, HbA1c, and SARS-CoV-2–specific IgG antibody levels, reflecting underlying metabolic characteristics and differences in humoral immune responses during the late post-COVID period. Conclusions: Post-COVID syndrome symptoms were frequently observed among older adults at the time of assessment, more than one year after SARS-CoV-2 infection, despite normalization of most laboratory parameters. In patients with T2DM, higher glucose, HbA1c, and antibody levels likely reflect underlying metabolic characteristics rather than a direct effect of post-COVID syndrome. Further longitudinal studies are warranted to clarify the long-term clinical significance of the observed metabolic and immunological findings. Full article

Background/Objectives: This report is an assessment of the characteristics associated with cardiovascular dysautonomia (CVD) in the context of long Coronavirus disease (COVID), which is currently inadequately characterized. Material and Methods: A retrospective cross-sectional study was performed involving 106 patients with long COVID, including 34 individuals diagnosed with CVD, among whom eight met the criteria for Postural Tachycardia Syndrome (PoTS). The variables assessed encompassed individual characteristics (e.g., age, sex, comorbidities), immunization parameters (e.g., vaccination/viral status, timing, frequency), cellular and humoral anti-Spike and anti-Nucleocapsid (Nuc) immune responses, inflammatory and allergic biomarkers, as well as an extensive panel of common autoantibodies comprising anti-nuclear antibodies, anti-central nervous system antibodies (cerebellum, brain), and anti-peripheral nervous system antibodies (gangliosides). Results: An age < 45 years, body mass index, hyperventilation syndrome as well as a higher cumulative number of antigenic contacts (vaccinations plus infections ≥ 3) and an elevated basophil count (≥0.06 G/L) were independently associated with CVD. There was no association between CVD and inflammatory markers or common autoantibodies. Patients with PoTS criteria had a strong anti-Spike cellular immune response and increased IgG anti-Nuc humoral immunity when compared with CVD and non-CVD long COVID counterparts. Conclusions: Compared to other long COVID patients, patients with long COVID-associated CVD have distinctive clinical and immunovirological features. Our results suggest the potential role of the immune response against Spike and of allergic pathways rather than humoral autoimmunity against common autoantibodies in long COVID CVD. Full article

Background/Objectives: Long COVID-19 (LC-19), also known as Post-Acute COVID-19 Syndrome (PACS), is a chronic condition some people experience after an initial SARS-CoV-2 infection. The etiology of this complex, multifactorial disease remains largely unknown, although various theories have been propounded. This study aims to profile and compare the metabolic activity of cells of normal and LC-19 patients. Methods: A cohort of 20 individuals, 10 with LC-19 and 10 without LC-19, was selected based on their post-COVID-19 symptomatology. Saliva was tested for opportunistic viruses like Epstein–Barr virus (EBV) and Human Herpesvirus 6 (HHV-6). Lymphoblastoid cell lines derived from blood were analyzed using the Biolog Phenotype Mammalian Microarrays (PM-M1, PM-M6, and PM-M7) to assess metabolic activity across a wide array of growth substrates and effector molecules. Results: Unique metabolic profiles emerged across the controls and LC-19 groups. The SARS-CoV-2 infection causes an over two-fold enhanced utilization of glycolytic and anaerobic substrates and a reduced response to growth factors and effectors. The increased energy source utilization assessed in PM-M1 is unsustainable, and the LC-19 groups demonstrate this with a clear correlation with the number of LC-19 symptoms, demonstrating a trend consistent with metabolic reprogramming. The infection also results in a reduced response to growth factors and effectors, assessed in PM-M6 and PM-M7, with the level of reduction commensurate with the symptom burden. Conclusions: The data from the patient groups were analyzed and compared to construct a metabolic profile unique to individuals who developed LC-19, which could, in the future, be used for diagnosis and to identify targets for therapeutic intervention. Our study identified an LC-19-specific metabolic profile indicative of adaptive responses to stress, cellular dysfunction, and prolonged inflammation, leading to the reprogramming of bioenergetic pathways. Full article

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 syndrome (LC) show substantial clinical overlap, but direct comparative microbiome studies remain limited. Methods: In this cross-sectional study, we compared the fecal gut microbiome of patients with ME/CFS, LC, and healthy controls (HC) within a unified analytical framework using 16S rRNA profiling, differential abundance testing, and multivariate modeling. We also examined associations between microbiome variation and questionnaire-derived symptom-domain scores. Results: Alpha-diversity did not differ significantly among groups, whereas beta-diversity analyses showed small but significant disease-associated community differences with broad overlap between cohorts. Differential abundance analysis identified stronger signals in disease-versus-control contrasts than in the direct ME/CFS vs. LC contrast. Both ME/CFS and LC shared enrichment of Sutterella and depletion of Terrisporobacter and Lachnospiraceae relative to HC. Predicted functional profiling showed shared disease-versus-control changes in pathways related to anaerobic acetate/H₂ carbon flow, inositol/polyol degradation, phosphonate/C1-related metabolism, and lysine-derived fermentation. Regression analyses showed the strongest microbiome associations with fatigue-related and physiosomatic domains, while affective, cognitive, and gastrointestinal outcomes showed weaker signals. Conclusions: Overall, these findings support the presence of overlapping but non-identical gut microbiome alterations in ME/CFS and LC. The results provide a basis for future longitudinal and multi-omics studies aimed at clarifying the stability, functional relevance, and clinical utility of these microbial patterns. Full article

Objectives: This study aimed to estimate the prevalence of Post-COVID-19 Syndrome among older adults in Indonesia, using time-based definitions of symptoms persisting beyond >4 weeks, >8 weeks, and >12 weeks. Methods: A retrospective cohort study was conducted among 329 older patients (≥60 years) hospitalized with COVID-19 in two tertiary hospitals in Jakarta from January to December 2021. Data on risk factors and persistent symptoms were collected from medical records and interviews. Results: The prevalence of Post-COVID-19 Syndrome was 31% (>4 weeks), 18.24% (>8 weeks), and 10.64% (>12 weeks). Significant predictors included frailty (OR 2.814), immobility during hospitalization (OR up to 4.767), higher number of initial symptoms (OR 2.043), constipation, instability, and sensory impairment during follow-up. Conclusions: Frailty, symptom burden, and geriatric syndromes, particularly immobility are strongly associated with Post-COVID-19 Syndrome in older adults. Clinical Implications: Early identification of frailty, geriatric syndromes (especially immobility), and high initial symptom burden is essential for risk stratification, targeted monitoring, and implementation of preventive and rehabilitative interventions to reduce long-term post-COVID-19 complications in older populations. Full article

Background/Objectives: Post-COVID syndrome (PCS) is frequently associated with persistent cognitive complaints such as fatigue and impaired concentration, yet objective markers related to cognitive dysfunction are lacking. Pupillary oscillation metrics have emerged as non-invasive indicators of task-related cognitive load and autonomic regulation. This study investigated the Index of Pupillary Activity (IPA) and the Low/High Index of Pupillary Activity (LHIPA) in a large cohort of patients with PCS compared with healthy controls. Methods: In this cross-sectional study, 526 participants (397 PCS patients, 129 controls) performed a standardized virtual reality-based stereoscopic task at three disparity levels: 275 arcsec (high difficulty), 550 arcsec (medium difficulty), and 1100 arcsec (low difficulty), using a head-mounted display with integrated eye tracking. Continuous pupillometry data were recorded, and IPA and LHIPA were calculated. Linear mixed-effects models with random intercepts for participants were applied, adjusting for age, sex, and task difficulty. Results: Both IPA and LHIPA were significantly lower in PCS patients than in controls at all three task difficulty levels in post hoc model-based contrasts. In adjusted mixed-effects models, PCS was also associated with lower overall IPA ($\beta =-0.111$, 95% CI $-0.160$ to $-0.062$, $p<0.001$) and lower overall LHIPA ($\beta =-0.164$, 95% CI $-0.253$ to $-0.074$, $p<0.001$). Lower task difficulty was associated with higher values of both metrics: for IPA, $\beta =0.164$ at 550 arcsec and $\beta =0.287$ at 1100 arcsec (both $p<0.001$); for LHIPA, $\beta =0.161$ at 550 arcsec and $\beta =0.254$ at 1100 arcsec (both $p<0.001$), relative to 275 arcsec. Thus, both indices showed an inverse association with task difficulty. Age was negatively associated with both metrics, whereas male sex was positively associated with both. No significant interaction between cohort and task difficulty was observed. Conclusions: PCS was associated with reduced IPA and LHIPA during a standardized stereoscopic task. These findings indicate altered task-related pupillary dynamics in PCS and may reflect altered cognitive-load processing and autonomic regulation. LHIPA, and with caution also IPA, may contribute to the objective assessment of task-related pupillary alterations in PCS. Full article

Excitotoxicity is one of the factors that participates in neurodegeneration, impairing neuronal and glial cells’ function, and leading to the development of chronic neurodegenerative diseases. The main mechanism of action lies in the overstimulation of excitatory receptors, especially the NMDA (N-methyl-D-aspartic acid) receptor, by glutamate, which promotes a massive influx of Ca²⁺ that is not sufficiently buffered by the intracellular machinery, or not released by mechanisms such as Ca²⁺ ATPase and plasma membrane Ca²⁺/Na⁺ exchanger promoting, among other toxic effects, mitochondrial damage and an increase in reactive oxygen species (ROS). Notably, many cases reported of long COVID-19 describe significant brain alterations and neuropsychiatric disorders, including delirium, depression, etc., and patients required increased use of antidepressant or anxiolytic drugs, for example. In addition, emerging evidence links neurodegeneration as a potential long-term sequelae associated with an increased number of patients with cognitive disorders. This review analyzes data from the literature regarding brain alterations associated with post-COVID-19 syndrome and explores a potential link to the excitotoxicity pathways, due to its participation in neurodegeneration by homeostatic failure, and it is clearly present in various brain conditions, such as Alzheimer’s and Parkinson’s diseases. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long Coronavirus Disease 2019 (long COVID) are complex chronic conditions that often follow infectious triggers with overlapping clinical features but poorly defined pathophysiological relationships. This study aimed to identify disease-specific immune signatures through multiparameter immunophenotyping of monocytes, dendritic cells, and T cell subsets. A total of 207 participants were included (ME/CFS: n = 103; long COVID: n = 63; healthy controls: n = 41). Peripheral blood mononuclear cells were analyzed using multiparameter flow cytometry. Statistical analyses included non-parametric testing, age-adjusted Analysis of covariance (ANCOVA), correlation network analysis, and principal component analysis (PCA). Long COVID was characterized by increased M2-like monocyte polarization, elevated CD80 expression across monocyte subsets, expansion of dendritic cells, and reduced expression of activation markers, indicating persistent immune activation with features of immune exhaustion. In contrast, ME/CFS exhibited reduced costimulatory molecule expression, impaired C-C chemokine receptor type 7 (CCR7)-mediated immune cell trafficking, and less coordinated activation patterns, consistent with a state of immune suppression. Correlation network analysis revealed more extensive and integrated immune interactions in long COVID, while PCA identified distinct immunophenotypic components and enabled moderate discrimination between the two conditions. These findings demonstrate that ME/CFS and long COVID are characterized by distinct immune profiles, supporting the concept of divergent immunopathological mechanisms. The identified signatures may contribute to biomarker development and guide targeted therapeutic approaches. Full article

Objectives: The association between osteonecrosis (ON) and Coronavirus Disease of 2019 (COVID-19) was reported early during the pandemic. ON of the femoral head (ONFH) is particularly problematic, as it may destroy the joint and lead to arthroplasty, although early diagnosis and treatment might mitigate its progression. The aim of the present study was to quantify the prevalence of symptomatic and asymptomatic ONFH in patients with severe COVID-19 treated with high doses of corticosteroids during the first pandemic wave. Methods: For this prospective, observational, monocentric cohort study, patients were selected according to the risk factors described for severe acute respiratory syndrome coronavirus in 2002–2004 (SARS-1): young males (<61 years old), high cumulative cortisone doses (≥2 g), severe disease, and followed up clinically and with magnetic resonance imaging. ONFH was classified with the ARCO classification. Results: Out of 1944 patients admitted for COVID-19 from 23 February to 21 May 2020, 856 of 1944 were treated in ICU; 30/1944 were selected according to the inclusion criteria and 27 of 30 were enrolled. The mean age at admission was 54 years (range, 42–60). The mean dose of cumulative cortisone was 6.25 g (range, 2–16). A total of 4/27 (15%) patients had ONFH; only 2 of 4 (50%) were symptomatic, including 1 with multiple ON of major joints. Conclusions: A high-risk cohort of patients with COVID-19 and high doses of corticosteroids had a 15% rate of ONFH, and 2 years after the event, 50% of them were asymptomatic. For those patients, relying solely on clinical evaluation would risk underestimating ONFH, potentially influencing treatment and outcomes. Moreover, other joints might develop ON. The data collected in the present study can be considered for the management of long-COVID. The association between severe COVID-19, high doses of corticosteroids and ONFH suggests the need for focused clinical and magnetic resonance imaging, considering the high rate of asymptomatic patients. Full article

Background: Persistent pain, neuropathic symptoms, dyspnea, and impaired quality of life are common components of post-COVID syndrome. However, the long-term trajectory of these symptoms and the factors associated with persistent pain remain incompletely understood. Methods: This longitudinal cohort study included 80 patients previously hospitalized with COVID-19. Participants were evaluated at approximately 1, 4, and 8 months after discharge. Pain severity was assessed using the Visual Analog Scale (VAS), neuropathic symptoms using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, dyspnea using the modified Medical Research Council (mMRC) scale, functional limitation using the Post-CO9VID Functional Status (PCFS) scale, and health-related quality of life using the EQ-5D-5L and EQ-VAS scales. Functional performance was additionally assessed using the 30 s chair stand test and the Modified Borg Scale. Multivariable linear regression and logistic regression analyses were performed to identify predictors of reduced quality of life and persistent pain at 8 months. Results: A total of 80 patients were included in the study. Median VAS score decreased from 3.0 (0–6) at 1 month to 0 (0–0) at 4 months and 1 (0–1) at 8 months (p < 0.001). Median LANSS score decreased from 0 (0–2) at 1 month to 0 (0–0) at 4 and 8 months (p < 0.001), while the proportion of patients with LANSS ≥ 12 declined from 11.3% to 2.5%. EQ-5D index scores improved from 0.81 (0.72–0.91) to 0.93 (0.88–0.96) during follow-up (p < 0.001). Dyspnea severity, exertional symptoms, and functional limitation also improved significantly over time. Most of the clinical recovery occurred between the 1-month and 4-month evaluations, although smaller but significant improvements continued until 8 months for pain severity, functional performance, and quality-of-life measures. Older age, baseline dyspnea, anxiety, and higher baseline LANSS scores were independently associated with lower EQ-VAS scores at 8 months, whereas only higher baseline LANSS scores remained independently associated with persistent pain. Conclusions: Patients hospitalized with COVID-19 experience persistent pain, dyspnea, neuropathic symptoms, and reduced quality of life during follow-up, although most symptoms improve substantially over time. Early neuropathic symptom burden and baseline dyspnea may help identify patients at risk of poorer long-term recovery, although the associations should be interpreted cautiously. Full article

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID-19 syndrome share a symptom profile, including severe fatigue, cognitive dysfunction, exertional intolerance, sleep disturbances, hypervigilance, and the paradoxical state of being “wired but tired.” A well-established finding is sympathetic hyperactivity with reduced vagal tone, typically interpreted as autonomic nervous system dysfunction. Emerging evidence, however, suggests a broader disturbance across multiple neurotransmitter systems. This paper reviews current knowledge on neurotransmitter systems implicated in ME/CFS and Long COVID, focusing on potential mechanisms of dysregulation and their roles in disease pathology and symptom generation, as well as implications for treatment. In addition to abnormalities of the noradrenergic system, disturbances in serotonergic, GABAergic, and glutamatergic signaling have been reported. Contributing factors may include autoimmunity, neuroinflammation, gut dysbiosis, epigenetic influences, and stressors such as orthostatic intolerance, metabolic strain, and pain. A shift favoring excitatory over inhibitory neurotransmission can lead to excessive neural activation, autonomic dysfunction, sensory hypersensitivities, sleep disturbances, and cognitive impairment. Reduced GABAergic tone combined with increased glutamatergic and noradrenergic activity may elevate skeletal muscle tone, contributing to calcium overload, mitochondrial dysfunction, exertional intolerance, and post-exertional malaise. Various pharmacological treatments may partially rebalance these neurotransmitter systems, but limited efficacy highlights the need for systematic investigation and individualized strategies. Full article

Background and Clinical Significance: Osmotic demyelination syndrome (ODS) and pituitary apoplexy are rare but potentially severe neurological and endocrine complications that can arise in the context of profound metabolic stress. Case Presentation: We describe the case of a previously healthy 34-year-old man who developed severe symptomatic hyponatremia shortly after receiving his second dose of an mRNA COVID-19 vaccine. Initial laboratory findings and clinical assessment were consistent with syndrome of inappropriate antidiuretic hormone secretion. Following correction of serum sodium, the patient experienced neurological deterioration with gait disturbance, dysarthria, and cognitive impairment. Follow-up brain MRI demonstrated extrapontine osmotic demyelination involving the basal ganglia and thalamus, despite initially normal imaging. During subsequent endocrinological follow-up, pituitary MRI revealed pituitary apoplexy in a previously unrecognized adenoma, accompanied by evolving partial hypopituitarism. The patient was managed with careful electrolyte control and long-term hormone replacement therapy, including hydrocortisone, levothyroxine, and recombinant growth hormone, resulting in gradual functional and cognitive improvement. Conclusions: This case highlights the interaction between severe hyponatremia, osmotic stress, and pituitary vulnerability, and emphasizes the need for cautious sodium correction, careful interpretation of temporal associations, and continued clinical vigilance in the context of COVID-19 vaccination programs. Full article

SARS-CoV-2 infection is associated with not only acute respiratory symptoms but is also characterized by strong neurotropism which may contribute to the development of the multisystem post-COVID syndrome (PASC). Patients frequently report chronic neurocognitive disorders such as brain fog, significant attention deficits and increased susceptibility to epileptiform discharges. The aim of this review is to systematize the knowledge regarding deviations in quantitative electroencephalography (QEEG) recordings in convalescents and to evaluate the utility of this method as an objective biomarker. This work constitutes a comprehensive literature review integrating the latest data on neuroinflammation, blood-brain barrier damage and changes in cortical oscillatory dynamics induced by the infection. The literature analysis indicates that the virus may induce a pathological excitation and inhibition imbalance (E/I imbalance) in neuronal networks. In QEEG studies this manifests as excessive activity of slow bands (Theta, Delta), a deficit of rhythms responsible for attention and sensorimotor integration (SMR) and a pathologically elevated Theta to Beta ratio (TBR). In conclusion, QEEG can serve as an objective and highly sensitive tool supporting the diagnosis and stratification of patients with neurocognitive complications of Long COVID. The integration of precise electrophysiological phenotyping with targeted behavioral neuromodulation (e.g., EEG-Biofeedback) fits into the paradigm of personalized medicine and offers a prospective strategy for mitigating long-term neurological burdens. Full article

Background and Objective: After SARS-CoV-2 infection, Long COVID (LC) syndrome has occurred in a high proportion of patients, affecting their health. The aim of this study was to estimate the incidence of LC, as well as its risk and protective factors. Materials and Methods: We conducted a prospective population-based cohort study of the Borriana COVID-19 cohort (Castellon Province, Valencia Community, Spain) from May 2020 to August 2023, with a follow-up of 40 months, using the LC definition given by the World Health Organization. Inverse probability-weighted regression adjustment was applied in the statistical analysis. Results: With a participation rate of 63.8% and a total of 722 participants, the mean age was 37.7 ± 17.4 years, and 460 (62.3%) were female. Among them, 644 had experienced a SARS-CoV-2 infection, and 184 developed LC, corresponding to a cumulative incidence of 28.6%. At the time of follow-up, 135 patients remained affected by LC, and one LC-related death was recorded. Significant risk factors for LC included older age, female sex, being part of a small family, having a chronic disease, SARS-CoV-2 exposure, and disease severity. Asymptomatic COVID-19 infection and SARS-CoV-2 vaccination were significantly protective factors. Conclusions: A substantial incidence of LC was observed, along with a low recovery rate. Several risk and protective factors were identified. Continued follow-up of this cohort, improved medical care for patients with non-recovered LC, ongoing surveillance of SARS-CoV-2 infections, and vaccination of the at-risk populations against SARS-CoV-2 are recommended. Full article

Background/Objectives: Cognitive dysfunction, or “brain fog”, following COVID-19 viral infection is strongly associated with diminished work capacity which disproportionality affects working-age adults. This study examined an existing method of cognitive rehabilitation training applied to adults struggling with workplace functioning and self-efficacy due to post-COVID-19 brain fog. Methods: Nine adults with post-COVID-19 cognitive dysfunction participated in this single arm pilot trial of a severity-adaptive cognitive training program. The participants completed 45–90 h of clinician-delivered cognitive training exercises delivered remotely in 60- to 90-min sessions, two or three times per week. The primary outcome measure was overall workplace self-efficacy with subskills of perceived workplace functioning, perception of cognitive functioning, and perception of home functioning assessed through pre and post surveys and qualitative interviews. The secondary outcome was cognitive function operationalized by an IQ score administered before and after the intervention. Results: The participants achieved significant improvements in workplace self-efficacy and cognition following cognitive training. The main qualitative themes of self-reported improvements were in executive function, health and energy, daily living activities, productivity, and socioemotional functioning. A cross-case synthesis of pre-intervention struggles, and post-intervention improvements revealed subthemes at work or school in cognitive processing and comprehension, memory, executive function, fatigue, emotional distress, confidence in work or academics, and work/academic performance impairment. As a group, the mean gain in IQ score was 10.5 points. Conclusions: This study adds to the growing body of literature examining the possibility of using cognitive rehabilitation for post-COVID-19 cognitive dysfunction impacting workplace self-efficacy and work functioning. Full article