Search Results (521)

Background/Objectives: Post-COVID syndrome (PCS) remains a clinically heterogeneous condition. In patients with chronic diseases, real-world evidence is needed to describe its frequency and to identify clinical factors associated with its current presence. This study assessed the prevalence of PCS and factors associated with current PCS status among patients with chronic diseases. Methods: This observational cross-sectional study included a consecutively enrolled source clinical sample of 850 adults receiving inpatient or outpatient care in Almaty and the Almaty Region between June and December 2025. The primary analytic cohort comprised participants with documented prior COVID-19 (n = 250). PCS was assessed at study enrollment according to the national clinical protocol as current symptoms persisting for more than 12 weeks and not explained by an alternative diagnosis. Multivariable logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). COVID-19 vaccination was excluded from the primary model and evaluated only in a sensitivity analysis because vaccination timing relative to infection was unavailable. The exploratory association-based probability model was evaluated using the AUC with 95% CI, Brier score, calibration assessment, bootstrap internal validation with 1000 resamples, assessment of age nonlinearity, and decision curve analysis. Results: PCS was identified in 147 of 250 participants with prior COVID-19 (58.8%). In the revised primary multivariable model, age (OR = 1.24 per 10-year increase; 95% CI: 1.01–1.54; p = 0.040) and endocrine diseases (OR = 3.36; 95% CI: 1.69–6.98; p < 0.001) remained associated with current PCS status. The association with endocrine diseases persisted after adjustment for body mass index. The apparent AUC was 0.687 (95% CI: 0.620–0.753), and the Brier score was 0.218. Bootstrap internal validation yielded an optimism-corrected AUC of 0.655, a calibration intercept of 0.061, and a calibration slope of 0.816. Conclusions: PCS was frequent among patients with chronic diseases who had prior COVID-19. Older age and endocrine pathology were the most consistent factors associated with current PCS status. All model-performance estimates were obtained within the development sample; the model should not be used for individual prediction or follow-up planning without prospective external validation. Full article

Post-exertional malaise (PEM) and cognitive dysfunction (hereafter “cognitive dysfunction”, including the patient-reported syndrome often described as “brain fog”) are among the most disabling features of Long COVID; yet, approved disease-modifying treatments remain lacking. Emerging evidence implicates interacting disturbances in mitochondrial bioenergetics, redox regulation and neurovascular inflammation, although much of the supporting evidence remains indirect and derives from acute COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), primary mitochondrial disease, inflammatory biology and mechanistic pharmacology rather than from direct Long COVID intervention trials. This hypothesis-generating narrative review develops a mechanism-based translational framework: that a pathway-targeted nutraceutical programme may modulate selected elements of these three axes, subject to prior demonstration of formulation quality, pharmacokinetic feasibility, target engagement and safety. Candidate modules comprise coenzyme Q10 and alpha-lipoic acid for bioenergetic/redox support; selenium, sulforaphane and resveratrol for Nrf2–thioredoxin-related redox regulation; and Boswellia serrata, luteolin and eicosapentaenoic acid for putative prostaglandin/resolution-pathway modulation. Sonlicromanol provides a conceptual mechanistic precedent for combined redox and prostaglandin-directed pharmacology, but it is not considered pharmacologically equivalent to an eight-agent nutraceutical combination. We summarise the mechanistic rationale, distinguish direct from indirect evidence, define qualitative evidence-grading criteria, outline safety and interaction considerations, and propose a staged translational research programme. This framework is intended to generate falsifiable hypotheses for future Long COVID studies, not to imply established clinical efficacy. Full article

Coronavirus disease 2019 (COVID-19) is increasingly recognized as a multisystem disorder associated with persistent metabolic complications extending beyond the acute phase of infection. Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may disrupt glucose homeostasis through mechanisms involving pancreatic β-cell dysfunction, insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and hypoxia-related signalling. This review summarizes current evidence regarding the molecular and cellular mechanisms linking SARS-CoV-2 infection to impaired insulin secretion and post-COVID metabolic disturbances. Particular emphasis is placed on the regulation of insulin secretion, β-cell compensation and failure, oxidative stress, inflammatory signalling, mitochondrial dysfunction, and the development of the post-COVID metabolic phenotype. Emerging evidence indicates that persistent metabolic abnormalities after COVID-19 may range from transient dysglycaemia to new-onset diabetes mellitus and metabolic syndrome. The review also discusses clinical implications, biomarkers, therapeutic perspectives, and unresolved questions regarding the reversibility of post-COVID β-cell dysfunction. A better understanding of the mechanisms underlying post-COVID metabolic dysfunction may improve risk stratification, facilitate early intervention, and support development of targeted therapeutic strategies aimed at preserving β-cell function and long-term metabolic health. Full article

Residual inflammation remains a hallmark of treated HIV infection despite durable viral suppression. Whether previous SARS-CoV-2 infection is associated with residual inflammation in people living with HIV (PLWH) remains incompletely understood. This study evaluated the association between previous COVID-19 and persistent inflammation in virally suppressed PLWH. In this retrospective observational single-center study, 286 adults receiving antiretroviral therapy between January 2023 and December 2025 were included. Patients were stratified according to documented SARS-CoV-2 infection history. A secondary analysis included 231 individuals with sustained viral suppression (HIV-RNA < 50 copies/mL). Inflammatory biomarkers, immune recovery parameters, metabolic characteristics, and independent predictors of elevated inflammatory biomarker levels were evaluated. Previous SARS-CoV-2 infection was associated with significantly higher concentrations of C-reactive protein, interleukin-6, tumor necrosis factor-α, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (all p < 0.01). Among virally suppressed patients, elevated inflammatory biomarker levels were associated with lower CD4+ T-cell counts, lower CD4/CD8 ratios, obesity, metabolic syndrome, dyslipidemia, and hepatic steatosis. Previous SARS-CoV-2 infection, obesity, metabolic syndrome, and CD4+ T-cell counts < 500 cells/mm³ were independently associated with elevated inflammatory biomarker levels. Previous SARS-CoV-2 infection was independently associated with an unfavorable inflammatory profile in virally suppressed people living with HIV. Given the retrospective observational design, these findings should be interpreted as associations rather than evidence of causality. These findings suggest that long-term host-related and metabolic factors may contribute to residual inflammation beyond viral control and highlight the need for prospective studies investigating strategies to reduce residual immune activation in treated HIV infection. Full article

Background: Post-acute sequelae of COVID-19 (PASC), commonly known as long COVID, affects an estimated 10–30% of SARS-CoV-2 non-hospitalised and 50–70% of hospitalised survivors. This condition remains clinically heterogeneous, and the specific mechanisms driving the transition from acute infection to chronic sequelae remain poorly understood. We assessed independent risk factors, tracked the evolution of clinical features, defined distinct symptom-based phenotypes, and assessed the impact of different pandemic waves on the likelihood of developing long COVID in hospitalised survivors. Methods: We conducted a single-centre, retrospective cohort study at a university hospital in London. The population comprised 627 adults hospitalised with acute COVID-19 between February 2020 and December 2022. Baseline characteristics and outcomes were compared between long COVID and resolved cases using appropriate statistical tests for continuous and categorical variables. Multivariable logistic regression identified risk factors. McNemar’s test quantified the phenotypic shift from admission to follow-up. Latent Class Analysis (LCA) identified clinical subtypes based on symptom clusters. Results: Of 627 patients, 252 (40.2%) met long COVID criteria. Comorbidity burden was the strongest predictor; patients with a single condition had a 4-fold increase in odds (aOR 4.62, 95% CI 2.36–9.04). The ORs were also significantly elevated among patients with 2 (aOR 3.26), 3 (aOR 2.68), or 4 or more (aOR 3.24) comorbidities. Older age (aOR 1.04), acute disease severity (measured by length of hospital stay) (aOR 1.27 per log-day) and elevated admission fibrinogen (aOR 1.21 per g/L) were significant predictors. Temporal analysis revealed a precipitous decline in risk from Wild-type/Alpha (>50%) to Delta/Omicron (<21%). We observed a distinct phenotypic shift: while acute respiratory inflammation resolved, systemic fatigue increased fourfold (7.0% to 32.4%), and memory difficulties emerged in the post-acute phase. LCA identified two phenotypes: fatigue-dominant and multisystem phenotypes. Conclusions: Long COVID is a multifactorial syndrome driven by host susceptibility, acute severity, and persistent coagulopathy. Clinical management should move beyond a monolithic approach and favour phenotype-specific strategies. Full article

Background: This study evaluated the potential effects of different COVID-19 vaccine platforms (mRNA and inactivated) on acute coronary syndrome (ACS) through Galectin-3, a biomarker of chronic inflammation and fibrosis. It aimed to compare serum Galectin-3 levels among NSTEMI patients according to COVID-19 vaccination status and vaccine type. Methods: A total of 75 patients with NSTEMI were prospectively enrolled and categorized into three groups: inactivated vaccine recipients (n = 25), mRNA vaccine recipients (n = 25), and unvaccinated controls (n = 25). Serum Galectin-3 levels were measured to assess chronic inflammatory status. Additionally, markers of acute myocardial injury and inflammatory response were analyzed. Results: Galectin-3 levels were similar across the inactivated vaccine, mRNA vaccine, and unvaccinated NSTEMI group, with no statistically significant difference observed (p = 0.481). Although troponin I levels and acute inflammatory cell burden were higher in vaccinated patients compared with the unvaccinated NSTEMI group, Galectin-3 levels remained comparable among all groups. No significant differences in Galectin-3 levels were observed according to vaccination status or vaccine type. Conclusions: In this exploratory cohort of NSTEMI patients, serum Galectin-3 levels did not differ significantly according to COVID-19 vaccination status or vaccine type. These findings suggest no detectable association between vaccination history and Galectin-3 levels in the study population. Larger prospective studies with longitudinal follow-up are needed to confirm these observations. 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

Background/Objectives: AA amyloidosis is a serious complication of chronic inflammation, which may arise in the setting of inborn errors of immunity (IEIs) due to recurrent or persistent infections. Common variable immunodeficiency (CVID) is the most frequent symptomatic IEI in adults, yet its association with secondary AA amyloidosis remains rarely reported. Case presentation: We describe a 37-year-old male with a history of recurrent pneumonia, chronic sinusitis, and osteomyelitis with sepsis since childhood. At age 33, he developed bilateral pneumonia after COVID-19, followed by repeated lower respiratory tract infections. At age 36, nephrotic syndrome (proteinuria 10.69 g/day, hypoalbuminemia) led to kidney and gastric mucosa biopsies, which confirmed AA amyloidosis. Immunological workup revealed panhypogammaglobulinemia (IgG 0.1 g/L, IgA 0.01 g/L, IgM 0.28 g/L), markedly reduced switched memory B cells, and an inverted CD4⁺/CD8⁺ ratio. Chest CT showed bronchiectasis, bronchiolitis, and mediastinal lymphadenopathy. Whole-exome sequencing excluded known monogenic IEIs, autoinflammatory, or hereditary amyloidosis genes; a heterozygous likely pathogenic variant in ODAD2 (associated with primary ciliary dyskinesia) was considered incidental. A diagnosis of CVID with secondary AA amyloidosis was established. Conclusions: This case illustrates that CVID may remain undiagnosed for decades and present with secondary AA amyloidosis as the first major complication. In any patient with nephrotic syndrome and a history of recurrent or unusual infections, an IEI should be actively excluded. Early recognition of CVID and appropriate immunoglobulin replacement therapy can prevent infectious exacerbations and potentially halt amyloid progression. 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

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

Kounis syndrome (KS) describes the occurrence of acute coronary syndromes precipitated by allergic, hypersensitivity, or anaphylactic reactions and represents a unique intersection between immunologic activation and cardiovascular disease. The epidemiology of KS is likely underestimated due to diagnostic overlap with other cardiac and allergic conditions and limited awareness across medical specialties. This narrative review focuses on the distinctive features of KS in special populations, emphasizing how patients’ age, comorbidities, immune status, and vascular substrate modify presentation, diagnosis, and outcomes. In elderly patients, polypharmacy, increased plaque vulnerability, and endothelial dysfunction favor Type II and III KS. Pediatric cases, although rare, are predominantly Type I and strongly associated with food allergies, insect stings, vaccines, and antibiotics, with under-recognition driven by diagnostic bias and ethical concerns surrounding invasive testing. Patients with coronary stents, cardiac devices, chronic kidney disease, and those receiving dialysis exhibit heightened susceptibility due to chronic inflammation, foreign-body hypersensitivity, and prothrombotic states. Pregnancy and the peripartum period represent a unique immuno-hemodynamic milieu in which Th2 immune shift, increased coronary vasoreactivity, and obstetric triggers can compromise both maternal and fetal perfusion. Additional risk modulation is observed in atopic individuals, asthmatics, patients with autoimmune, inflammatory, oncologic, psychiatric, and neurodevelopmental conditions, as well as in COVID-19 and post-infectious states. We propose a host-modified framework for KS that complements traditional classification by integrating immune phenotype and vascular substrate, enabling improved risk stratification and personalized preventive strategies. 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