Search Results (181)

Background: Acute kidney injury (AKI) is increasingly recognised in children with acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C), yet the long-term renal consequences in younger paediatric populations remain unclear. Most studies focus on acute illness or mixed-age cohorts, with limited data specific to children aged 0–12 years. Objectives: This study aimed to systematically identify, evaluate, and synthesise evidence on post-acute (≥30 days) and long-term (≥90 days) kidney outcomes following SARS-CoV-2 infection or MIS-C in children aged 0–12 years, including chronic kidney disease (CKD), eGFR decline, proteinuria, haematuria, hypertension, and need for kidney replacement therapy. Methods: We searched MEDLINE, Embase, CINAHL, and PubMed (December 2019–30 November 2025), following PRISMA 2020 guidelines and a registered PROSPERO protocol (CRD420251241949). Observational studies reporting kidney outcomes ≥30 days post-infection in children aged 0–12 years were included. Risk of bias was assessed using the Newcastle–Ottawa Scale or ROBINS-I. Owing to heterogeneity and absence of ≥3 comparable datasets, a narrative synthesis was performed. Results: Seven studies met inclusion criteria (five MIS-C cohorts, two acute COVID-19 cohorts). Only a subset provided extractable data specific to children aged 0–12 years. Follow-up ranged from 30 days to 12 months; four studies reported outcomes ≥ 180 days. Across all studies, no incident CKD, sustained eGFR decline, or kidney replacement therapy were reported among children completing long-term follow-up; however, most long-term outcome data were derived from MIS-C cohorts with median ages around 8–11 years that included some adolescents, rather than exclusively children aged 0–12 years. One MIS-C study reported long-term hypertension in 14% of children. A cross-sectional Italian cohort of mild COVID-19 demonstrated hyperfiltration, proteinuria, and microhaematuria at ~3 months, though chronicity could not be assessed due to absence of baseline values. A large US EHR-based cohort identified increased CKD risk after COVID-19 in the broader < 21-year population; however, 0–12-year-specific event counts were not reported, preventing quantitative synthesis for young children. Conclusions: Evidence on long-term kidney outcomes after SARS-CoV-2 infection in children aged 0–12 years remains limited, and only a small subset of studies provided extractable, age-specific data. On the other hand, MIS-C cohorts generally show favourable renal recovery, small sample sizes, lack of control groups, and short follow-up restrict confidence in these findings. Large paediatric EHR studies suggest potential long-term renal risk in broader paediatric populations, highlighting the need for age-stratified, prospective cohorts with serial eGFR, urine studies, and blood pressure assessments. Until definitive evidence emerges, structured renal follow-up may be warranted for children with AKI or MIS-C during COVID-19. Full article

This review article attempts to provide a unifying hypothesis to explain the myriad of symptoms and predispositions underlying the development of PASC (Postacute Sequelae of COVID), often referred to as Long COVID. The hypothesis described here proposes that Long COVID is best understood as a disorder of persistent immune dysregulation, with chronic macrophage activation representing the fundamental underlying pathophysiology. Unlike transient post-viral syndromes, Long COVID involves a sustained innate immune response, particularly within monocyte-derived macrophages, driven by persistent spike protein (peripherally in MAIT cells and centrally in Microglial cells), epigenetic imprinting, and gut-related viral reservoirs. These macrophages are not merely activated temporarily but also become epigenetically “trained” into a prolonged inflammatory state, as demonstrated by enduring histone acetylation markers such as H3K27acDNA Reprogramming. It is proposed that recognizing macrophage activation as the central axis of Long COVID pathology offers a framework for personalized risk assessment, targeted intervention, and therapeutic recalibration. Full article

Introduction: Immune dysfunction plays a significant role in Metabolic syndrome, contributing to both insulin resistance and chronic low-grade inflammation. This immune dysfunction is characterized by overproduction of inflammatory cytokines among which of primary importance are tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and (MCP-1), whereas others such as interferon gamma (IFN-γ), IL-17A, and the anti-inflammatory IL-10 appear to be of secondary importance. Cytokines also play a significant role in Post-COVID disorders contributing to prolonged immune dysregulation and persistent subclinical inflammation. However, their role in the newly emerging metabolic disorders following infection remains poorly defined. Methods and materials: In the current study 78 patients (26 men and 52 women) were included, divided into two groups—group 1 (individuals with newly diagnosed carbohydrate disorders after proven COVID-19 or Post-COVID group; n = 35) and group 2 (COVID-19 negative persons with Metabolic Syndrome; n = 33). They were further divided into several subgroups according to type of metabolic disorder present. Standard biochemical, hormonal and immunological parameters were measured using ELISA and ECLIA methods, as well as some indices for assessment of insulin resistance were calculated using the corresponding formula. Results: Patients from both groups demonstrate similar metabolic parameters including BMI and unadjusted lipid and uric acid levels (p > 0.05). After adjustment for age, sex, and BMI revealed significant differences, Post-COVID status independently predicted higher fasting glucose, HbA1c, total cholesterol, LDL-cholesterol, triglycerides, uric acid, and insulin-resistance indices, indicating substantially impaired glycemic and metabolic control beyond traditional risk factors. Furthermore, the Post-COVID cohort demonstrated marked cytokine dysregulation, with significantly elevated levels of TNF-α, IFN-γ, IL-17A, and IL-10 after adjustment. Conclusions: The observed changes in both metabolic and immune parameters studied among the two groups show many similarities, but some significant differences have also been identified. Together, these findings indicate that Post-COVID metabolic dysfunction is characterized by inflammation-driven dyslipidemia, heightened oxidative stress, and persistent immune activation, distinguishing it from classical Metabolic syndrome. Full article

Objectives: Neurodivergent (ND) individuals (e.g., autistic people) are more likely to experience health problems that are characterised by ‘Central Sensitisation’ (CS). Recent research suggests that a so-called ‘Long-COVID’ syndrome might also be explained by a heightened response to internal physiological stimuli, much like in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The primary objective of this study was to establish whether individuals who scored highly on a measure of CS would be more likely to experience long-term symptoms of COVID-19. A secondary aim considered if having a Type D personality was also linked to ongoing COVID-19 symptoms. Method: Using a standardised assessment tool, we examined whether traits associated with autism would predict long-term COVID-19 symptoms in 267 Healthcare Workers (HCWs). We also used a measure of Type D personality to establish if negative affect and social inhibition were related to Long-COVID. Results: A higher number of autistic traits predicted COVID-19 symptoms that lasted more than 12 weeks regardless of formal autism diagnosis. A personality measure also showed that negative affect was associated with experiencing COVID-19 symptoms for 4–12 weeks, though the direction of causality in this case is uncertain. Conclusions: Our main findings were (i) more HCWs scored above threshold for neurodivergence than those who were self-declared as having been diagnosed as neurodivergent; (ii) while there was no association between long-term COVID-19 and self-declared neurodivergent status, scores for the ‘sensory reactivity’ item of a standardised autism scale was predictive of COVID-19 symptoms lasting beyond 12 weeks post-infection; and (iii) HCWs with Type D Personality were not more likely to experience long-term COVID-19. Full article

Background: COVID-19 has taken millions of lives and continues to affect people worldwide. Post-Acute Sequelae of SARS-CoV-2 Infection (also known as Post-Acute Sequelae of COVID-19 (PASC) or more commonly, Long COVID) occurs in the aftermath of COVID-19 and is poorly understood despite its widespread effects. Methods: We created a machine-learning model that distinguishes PASC from PASC-similar diseases. The model was trained to recognize PASC-dysregulated metabolites (p ≤ 0.05) using molecular descriptors. Results: Our multi-layer perceptron model accurately recognizes PASC-dysregulated metabolites in the independent testing set, with an AUC-ROC of 0.8991, and differentiates PASC from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, postural orthostatic tachycardia syndrome (POTS), and irritable bowel syndrome (IBS). However, it was unable to differentiate fibromyalgia (FM) from PASC. Conclusions: By creating and testing models pairwise on each of these diseases, we elucidated the unique strength of the similarity between FM and PASC relative to other PASC-similar diseases. Our approach is unique to PASC diagnosis, and our use of molecular descriptors enables our model to work with any metabolite where molecular descriptors can be identified, as these descriptors can be generated and compared for any metabolite. Our study presents a novel approach to PASC diagnosis that partially circumvents the lengthy process of exclusion, potentially facilitating faster interventions and improved patient outcomes. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness with unknown etiology. An estimated 17–24 million people representing approximately 1% of the population are afflicted worldwide. In over half of cases, ME/CFS onset is associated with acute “flu-like” symptoms, suggesting a role for viruses. However, no single virus has been identified as the only etiological agent. This may reflect the approach employed or more strongly the central dogma associated with herpesviruses replication, which states that a herpesvirus exists in two states, either lytic or latent. The purpose of this review is to address the role that abortive lytic replication may have in the pathogenesis of ME/CFS and other post-acute viral infections and also to raise awareness that these syndromes might be poly-herpesviruses mediated diseases. Full article

Background: Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a debilitating condition characterized by persistent fatigue and multisystemic symptoms, such as cognitive impairment, musculoskeletal pain, and post-exertional malaise. Recently, parallels have been drawn between ME/CFS and Long COVID, a post-viral syndrome following infection with SARS-CoV-2, which shares many clinical features with CFS. Both conditions involve chronic immune activation, raising questions about their immunopathological overlap. Objectives: This study aimed to compare immune biomarkers between patients with ME/CFS or Long COVID and healthy controls to explore shared immune dysfunction. Methods: We analyzed lymphocyte subsets, cytokine profiles, psychological status and their correlations in 190 participants, 65 with CFS, 54 with Long COVID, and 70 healthy controls. Results: When compared to healthy subjects, results in both conditions were marked by lower levels of lymphocytes (CFS—2.472 × 10⁹/L, p = 0.006, LC—2.051 × 10⁹/L, p = 0.009), CD8⁺ T cells (CFS—0.394 × 10⁹/L, p = 0.001, LC—0.404 × 10⁹/L, p = 0.001), and NK cells (CFS—0.205 × 10⁹/L, p = 0.001, LC—0.180 × 10⁹/L, p = 0.001), and higher levels of proinflammatory cytokines such as IL-6 (CFS—3.35 pg/mL, p = 0.050 LC—4.04 pg/mL, p = 0.001), TNF (CFS—2.64 pg/mL, p = 0.023, LC—2.50 pg/mL, p = 0.025), IL-4 (CFS—3.72 pg/mL, p = 0.041, LC—3.45 pg/mL, p = 0.048), and IL-10 (CFS—2.29 pg/mL, p = 0.039, LC—2.25 pg/mL, p = 0.018). Conclusions: Notably, there were no significant differences between CFS and Long COVID patients in the tested biomarkers. These results demonstrate that ME/CFS and Long COVID display comparable immune and inflammatory profiles, with no significant biomarker differences observed between the two groups. Full article

Background/Objectives: COVID-19 infection is a respiratory illness that affects multiple body systems, including the musculoskeletal system. In August 2024, Colombia reported 6 million infections and a 2.2% mortality rate related to COVID-19. Post-COVID-19 syndrome (PCS) is a chronic condition occurring after the acute infection, typically characterized by fatigue, weakness, pain, and sarcopenia, impacting the patient’s quality of life (QoL). This systematic review aimed to identify musculoskeletal sequelae, including peripheral muscle strength, fatigue, and QoL, in patients with PCS. Methods: We searched the PubMed, Scopus, and Web of Science databases for cross-sectional, case–control, and cohort studies focusing on musculoskeletal sequelae in patients with COVID-19 infection published between 2020 and 2025. Study quality and risk of bias were assessed using the MINORS and the ROBINS-E scales, respectively. Results: Thirteen studies (n = 5657 patients) met the eligibility criteria. Seventy-six percent of studies indicated muscle weakness as the most common sequela, primarily in older adults and individuals with comorbidities (obesity, diabetes, and chronic obstructive pulmonary disease). General fatigue (reported in 76% of the studies) significantly influenced patients’ daily lives, whereas 90% of patients reported some level of deterioration in their QoL, primarily regarding mental health, bodily pain, and physical performance. Conclusions: Patients with PCS who required mechanical ventilation showed reduced muscle strength and poor physical performance, especially older adults. Inactive individuals had worse musculoskeletal sequelae, while physical activity was associated with better strength levels. Although QoL improved after 12 months, the combination of aerobic exercise with adequate nutrition is essential to promote muscle recovery, reduce fatigue, and improve overall functional capacity in post-COVID-19 patients. Full article

Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-COVID Syndrome (PCS) are chronic conditions that share relevant pathophysiological mechanisms. Conventional rehabilitation programs have often been associated with patient dissatisfaction and frequent adverse events (AEs), highlighting the need for safer and more effective clinical approaches. This study aims to compare the effects of a telerehabilitation program based on conscious movement with those of conventional low-intensity exercise in individuals with ME/CFS or PCS. Methods: This is a prospective, single-blind, three-arm, parallel, superiority randomized clinical trial. A total of 147 participants (aged 18–70) with ME/CFS or PCS will be recruited and randomly assigned to one of three groups: (a) conscious movement; (b) low-intensity exercise; or c) usual care. All interventions will be delivered via telehealth over 12 weeks, with weekly 45-min sessions combining health education and individually tailored exercises. Participants will be encouraged to practice daily using the provided materials. Adherence rates and potential AEs will be recorded. The primary outcome is the total score on the 14-item Chalder Fatigue Scale at 12 weeks (post-intervention). Secondary outcomes include heart rate variability, functional performance, pain intensity and interference, mental health, interoceptive awareness, quality of life, sleep quality and fear of movement. Measurements will be collected at baseline, post-intervention, and at 3-month follow-up. Discussion: Recent evidence suggests that both autonomic and cognitive activity modulate immune function. Conscious movement, which integrates exercise with interoception and mindfulness-based strategies, may provide greater benefits than low-intensity exercise alone. Study limitations should be considered when interpreting the results. Trial registration: Registered at ClinicalTrials.gov on 15 May 2025 (NCT06978582). Protocol version 4 (29 September 2025). Ethics Committee code: 2025-0180. Full article

Early-life infections can produce durable changes in immune function and behavior. We propose a mechanistic hypothesis positioning the mechanistic target of rapamycin (mTOR) as the link between peripheral inflammation and central nervous system dysfunction in pediatric post-infectious syndromes. Based on clinical, translational, and experimental literature, we outline a stepwise pathway. First, sustained mTOR activation skews T-cell and macrophage differentiation toward pro-inflammatory and autoimmune states. Second, endothelial mTOR signaling weakens tight junctions and increases vesicular transport, compromising blood–brain barrier integrity. Third, cytokines and sometimes autoreactive cells enter the brain and engage mTOR in microglia and neurons, driving neuroinflammation, impaired synaptic maintenance and plasticity, and neurotransmitter disruption. This framework accounts for features observed in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute neuropsychiatry syndrome (PANS/PANDAS) and yields testable predictions on pathway activity and barrier permeability. It also motivates targeted interventions that modulate mTOR-related processes in immune and endothelial compartments and within neural circuits in children. So, this article aims to outline a mechanistic framework linking infection-driven mTOR activation to post-infectious neuropsychiatric syndromes. Full article

Long-COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are disabling diseases characterised by ongoing fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome typically follows viral infections, whereas Long-COVID exclusively follows SARS-CoV-2 infection, with overlapping but distinct features. This review uses comprehensive searches of online databases to compare their clinical presentations, pathophysiologies, and treatments. Both Long-COVID and ME/CFS appear to involve multifactorial mechanisms, including viral persistence, immune dysregulation, endothelial dysfunction, and autoimmunity, though their relative contributions remain uncertain. Symptom management strategies are consistent, however. Cognitive behaviour therapy has been successful, and there are minimal drug treatments. Graded exercise therapy occupies a contested place, recommending individualised pacing and multidisciplinary rehabilitation. Common and exclusive mechanisms must be identified to formulate valuable therapies. A more significant body of research focusing on immune dysfunction as a pathogenic mechanism for advancing the disease and enabling more effective therapies and diagnostics is needed. Full article

Background and Objectives: Heart failure (HF) represents a clinical syndrome characterized by symptoms and signs such as fatigue, dyspnea, edema of the lower limb, or pulmonary rales. It usually occurs in elderly individuals due to decreased cardiac pumping function and/or increased diastolic ventricular filling pressures. The COVID-19 pandemic deeply altered many daily life habits, and one of the most affected groups of people were those with chronic diseases because of their need for regular medical follow-up. Furthermore, SARS-CoV-2 infection itself has been shown to exacerbate cardiovascular diseases (CVDs). Materials and Methods: This retrospective, observational, and comparative study aimed to characterize and compare patients with chronic heart failure hospitalized in the Cardiology Department of Medical Clinic II, Mureș County Emergency Clinical Hospital, in Târgu Mureș, Romania, between January and December 2019 (pre-pandemic), January and December 2021 (pandemic), and January and December 2023 (post-pandemic). Results: A total of 406 patients were analyzed: 202 patients hospitalized in 2019, 101 patients hospitalized in 2021, and 103 patients hospitalized in 2023. Women with HF were significantly older (median age 72 years) than men (median age 65 years; p < 0.001). During the pandemic, the median length of hospitalization increased (8 days vs. 7 days in the other periods). The pandemic period was also associated with a decrease in left ventricular ejection fraction (LVEF), as reflected by a higher incidence of patients with HF with reduced ejection fraction (42% during the pandemic; p < 0.01). Conclusions: During and after the pandemic, men exhibited significantly higher rates of right and left bundle branch blocks, as well as chronic obliterating artery disease of the lower limb. Left ventricular function declined during the pandemic in both men and women. Throughout the years, we observed distinct patterns between male and female patients regarding associated diseases or behaviours, suggesting lifestyle and psychological changes due to the COVID-19 pandemic. Full article

Background/Objectives: Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia characterized by excessive tachycardia during orthostatic stress. It is frequently observed in patients with syncope, Chronic Fatigue Syndrome (CFS), and post-COVID-19 syndrome (PCS), yet the underlying mechanisms may differ across these conditions. This study aimed to assess autonomic nervous system (ANS) function in patients with syncope, CFS of insidious onset, and CFS post-COVID-19 who presented with POTS, and to compare them with age- and sex-matched patients without POTS. Methods: In this retrospective cross-sectional study, 138 patients over 18 years of age were included following head-up tilt testing (HUTT). Patients were divided into six groups: syncope with and without POTS, CFS with insidious onset with and without POTS, and CFS post-COVID-19 with and without POTS. All participants underwent HUTT, cardiovascular reflex testing (CART) by Ewing, five-minute resting ECG with short-term Heart Rate Variability (HRV) analysis, and 24 h Holter ECG monitoring. Results: The prevalence of POTS across groups ranged from 5% to 7%. Female predominance was consistent across all subgroups. In syncope with POTS, hypertensive responses during HUTT, lower rates of normal Valsalva maneuver results, and reduced HF values in short-term HRV suggested baroreceptor dysfunction with sympathetic overdrive. In both CFS subgroups with POTS, CART revealed higher rates of definite parasympathetic dysfunction, along with more frequent extreme blood pressure variation during HUTT and reduced vagally mediated HRV parameters (rMSSD, pNN50). Across groups, no significant differences were observed with regard to long-term HRV across groups. Conclusions: Distinct autonomic profiles were identified in POTS patients depending on the underlying condition. Syncope-related POTS was associated with baroreceptor dysfunction and sympathetic predominance, whereas CFS-related POTS was characterized by parasympathetic impairment and impaired short-term baroreflex regulation. Evaluating dysautonomia patterns across disease contexts may inform tailored therapeutic strategies and improve management of patients with POTS. Full article

Autonomic nervous system (ANS) dysfunction has emerged as a central feature of post-infectious syndromes, including post-COVID syndrome (PCS), chronic fatigue syndrome (CFS), and late-stage Lyme disease. This cross-sectional study included 1036 patients evaluated in the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje,” divided into four groups: PCS, CFS after COVID-19, CFS of insidious onset, and Lyme disease. All patients underwent head-up tilt testing (HUTT), and serological testing was performed in accredited institutions. The Lyme disease group demonstrated the highest prevalence of positive HUTT responses and a significantly greater frequency of orthostatic hypotension and syncope. Approximately 50–65% of patients in the PCS and Lyme groups were positive for IgM antibodies against at least one microorganism, with more than 10% showing positivity for three or more pathogens. Logistic regression analysis revealed that, beyond classical hemodynamic parameters, antibody status served as a significant predictor of HUTT outcomes, with specific associations identified for HSV-1, HHV-6, Coxiella burnetii, Toxoplasma gondii, and Borrelia spp. Multinomial regression further indicated that negative IgG antibodies, particularly to HSV-1 and VZV, predicted Lyme disease group membership. These findings support the hypothesis that ANS dysfunction in post-infectious syndromes may be driven by persistent or prior infections, highlighting the need for integrative diagnostic approaches. Full article

We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and long COVID. Shared mechanisms—including oxidative stress, impaired mitophagy and dynamics, mtDNA damage, and metabolic reprogramming—contribute to ongoing energy failure and chronic inflammation. Recent advancements highlight new therapeutic strategies such as mitochondrial transfer, transplantation, and genome-level correction of mtDNA variants, with early preclinical and clinical studies providing proof-of-concept. This review summarizes current evidence on mitochondrial changes across aging and post-viral syndromes, examines emerging organelle-based therapies, and discusses key challenges related to safety, durability, and translation. Full article