Search Results (61)

Background: Post-COVID-19 condition (PCC) remains a public health concern due to persistent metabolic and inflammatory alterations, especially among ICU survivors. Oxidative stress is involved in PCC pathophysiology, and the Mediterranean diet may be associated with redox balance. Objective: To evaluate the association between Mediterranean diet adherence (main exposure variable) and oxidative stress/redox stress biomarkers (primary outcomes) in ICU survivors with persistent symptoms after severe COVID-19. Additionally, body composition and inflammatory markers were explored as secondary outcomes related to redox status. Methods: This cross-sectional study included 123 adult ICU survivors with PCC (51 ± 13.2 years; 53% men; 75% with obesity). Protein carbonyls, TBARS, sulfhydryl groups, glutathione, CRP, albumin, and IL-6 were measured. Diet adherence during post-COVID-19 outpatient follow-up was assessed using MEDAS, and body composition by DXA. Participants were categorized by the median score, and Poisson regression models were applied. Results: The median MEDAS total score was 4 (IQR 2–5), indicating overall low adherence to the Mediterranean diet. Lower adherence was associated with higher glutathione levels (p = 0.04), with no differences in pro-oxidant markers. Higher sulfhydryl levels were associated with lower body fat, higher appendicular skeletal muscle mass, and lower CRP and IL-6. Conclusions: Low adherence was frequent and associated with antioxidant differences. Redox status was also associated with body composition and inflammatory markers. Full article

Background: Post-COVID-19 Condition (PCC) causes persistent multisystem symptoms, reduced quality of life, and high healthcare needs. Data on patient experiences in Switzerland are scarce. Objective: To assess healthcare access, treatment pathways, waiting times, and insurance-related burden among individuals with PCC in Switzerland. Methods: We conducted a nationwide anonymous online survey between July and October 2025. Adults living in Switzerland with symptoms persisting ≥12 weeks after SARS-CoV-2 infection were eligible. Recruitment was conducted through support groups, social media, and specialized PCC consultations at several Swiss hospitals. The multilingual questionnaire covered demographics, symptoms, healthcare utilization, treatment experiences, and insurance issues. Results: A total of 333 individuals participated (81.7% women; mean age 45.8 years). The most frequent symptoms were fatigue (98.5%), brain fog (92.5%), post-exertional malaise (91.0%), sleep disturbances (82.3%), and musculoskeletal pain (80.8%). Only 12.6% reported early and adequate medical support, whereas 45.0% had to actively seek care themselves and 24.6% had received no support. General practitioners were the most frequently consulted providers (77.5%), followed by specialized PCC clinics (39.0%). Waiting times were prolonged: 32.1% waited 4–6 months, 32.4% >6 months and 10.8% reported no available consultation service. Satisfaction with care was modest (3.02/5). Difficulties with social insurance were reported by 42.6%, including missing benefits, lack of recognition, and prolonged procedures. Conclusions: Individuals with PCC in Switzerland face major barriers to timely and coordinated care. Strengthening primary care competencies, expanding multidisciplinary services, and implementing structured patient-centered pathways are urgently needed to improve outcomes and reduce long-term disability. Full article

Background/Objectives: There is wide variability in the available estimates on the burden of Long-COVID (LC), both among adults and children. Preliminary evidence suggests that this inconsistency may be due, at least in part, to the adoption of uneven diagnostic criteria, proposed by several international entities during the course of the pandemic, but no comprehensive evaluation has been performed so far to quantify the extent of variation among children. This systematic review and meta-analysis aims to update the available epidemiological estimates of LC among pediatric subjects, and to systematically appraise the degree of variability that can be attributed to the diagnostic criteria adopted. Methods: A systematic literature search identified cohort studies providing data on LC among children and adolescents with a previous SARS-CoV-2 infection. We computed (a) proportion and (b) head-to-head meta-analyses (a) to quantify the pooled rates of LC and LC-related symptoms, and (b) to assess the likelihood of developing LC based upon selected demographic and/or clinical characteristics, respectively. Results: In total, 52 cohort studies and 960,089 subjects were included. The pooled rate of LC was 18.1% (95% CI: 13.1–23.6), ranging from 16.2% to 21.6%, according to NIH or WHO diagnostic criteria, respectively. Fatigue, respiratory and neurological symptoms were most commonly reported by LC patients. Stratified analyses showed that females, adolescents (vs. children), subjects with comorbidities, and those with a previous severe COVID-19 (as compared to asymptomatic primary infections) were more likely to develop LC (all p < 0.05). In contrast, the likelihood of LC onset did not significantly vary between individuals with ≥1 anti-SARS-CoV-2 vaccine dose, versus the unvaccinated (pooled OR: 0.92; 95% CI: 0.61–1.41). Conclusions: Although the available estimates may largely vary depending on the adopted definition, LC affects a meaningful proportion of the pediatric population; as such, common clinical criteria and diagnostic approaches are urgently needed. Moreover, given the relevant methodological heterogeneity and the generally poor-to-fair quality of a large part of the available literature, high-quality studies adopting standardized methodologies are warranted to identify at-risk populations and guide the implementation of targeted follow-up strategies. Full article

Background: Post-COVID-19 conditions (PCCs) present a significant public health challenge due to a vast array of new or persistent health symptoms across subjects. The complex, multi-systemic nature of PCCs makes these conditions difficult to differentiate from other non-COVID-19 related medical conditions. While the Military Health System Data Repository (MDR) provides a robust supply of population-level encounter data, its high-dimensional structure poses challenges for knowledge discovery and outcome research. Objectives: The primary aim of this study was to identify novel manifestations of PCCs among active-duty service members, and model the probabilistic relationships between PCC-related diagnoses. We propose a machine learning workflow as an effective tool for knowledge discovery to statistically validate candidate PCCs from large datasets. Methods: We conducted a retrospective cohort study using MDR records from July 2018 to June 2023. From an initial pool of 311,367 eligible Active-Duty Tricare beneficiaries, we isolated 101,789 COVID-19 infections and matched them 1:1 with uninfected controls (N = 203,578 total) based on age, sex, and propensity for COVID-19. Encounter data was mapped to 392 clinical categories using the Healthcare Cost and Utilization Project (HCUP) Clinical Classification Software Refined (CCSR). Candidate PCC categories were isolated using a cross-validated lasso regression model optimized with a Tree of Parzen Estimators algorithm. A consensus Bayesian Network structure was fitted to model potential probabilistic dependency structures between identified PCCs and prior COVID-19 diagnosis. Finally, conditional Cox proportional hazards models were used to statistically validate selected novel conditions using larger cohorts drawn from the same initial eligible pool by matching cases 1:2 with controls. Results: Feature selection reduced the diagnosis set by 97.96%, isolating 8 clinical categories from the initial 392. The model confirmed known PCCs, such as respiratory symptoms and malaise, and identified two potentially novel candidate PCCs: tinnitus and personality disorders. Survival analysis validated the selection of tinnitus, showing a significant association with COVID-19 (HR: 1.17, 95% CI: 1.12–1.22). No significant association was found between COVID-19 infection and personality disorders (HR: 1.11, 95% CI: 0.97–1.26). Conclusions: This study demonstrates an effective analytical pathway for addressing the limitations of analyzing complex, high-dimensional healthcare billing data. The methodology successfully generated testable hypotheses, identifying tinnitus as a relevant sequela, and is generalizable to future research involving unknown health outcomes related to prior infection. Full article

Introduction: Vaccination against COVID-19 has been crucial in controlling the pandemic. While side effects are typically mild, rare neurological complications have been reported. This is a case series of ten patients who reported of persistent fasciculations after COVID-19 vaccination. Methods: We describe the clinical presentation and diagnostic work-up of ten patients with new-onset fasciculations in temporal proximity to COVID-19 vaccination. Patients with prior SARS-CoV-2 infection or known alternative causes of fasciculations were excluded. Routine clinical data, including neurological examination, laboratory results, and electrophysiology (electromyography and nerve conduction studies), were analyzed. Results: Ten patients (5 male, 5 female; mean age 42.4 years) reported fasciculations beginning within 6 h to 13 days post-vaccination and persisting for 2–12 months at the time of presentation. Fasciculations were accompanied by additional symptoms such as paresthesia and fatigue. Laboratory results were mostly unremarkable; two patients had positive myositis antibodies without clinical correlates. Electrophysiology was unremarkable in six patients, while fasciculation potentials were detected in four patients. Nine were diagnosed with probable benign fasciculation syndrome (BFS), and one met diagnostic criteria for amyotrophic lateral sclerosis (ALS). Discussion: In this small, retrospective case series, most cases of post-vaccination fasciculations were benign and compatible with BFS. Whether BFS onset was causally linked to vaccination or due to a nocebo effect remains unclear. One patient was diagnosed with ALS, though a causal link remains speculative given the study’s limitations and rarity of similar reports. Larger, prospective studies are needed to validate these observations and explore underlying pathophysiological mechanisms. Full article

Background: Post-COVID-19 condition (PCC) is a complication following acute COVID-19 infection, which may lead to long-term cardiac abnormalities. This review aimed to assess the prevalence of structural/functional deviations in echocardiography in individuals with PCC compared to patients without PCC. Methods: We searched three databases. Two reviewers independently screened articles using LASER Al and extracted relevant data using a piloted Excel sheet. We performed meta-analysis using OpenMeta and RevManWeb and a subgroup analysis based on patients’ settings during acute COVID-19. We assessed the risk of bias using the Hoy et al. tool and the certainty using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 16 studies that reported on differences in echocardiographic findings in patients with or without PCC. Individuals with PCC were more likely to have structural/functional deviations in echocardiographic readings of unclear clinical significance, particularly those who were hospitalized during acute COVID-19. The overall certainty of the evidence was very low due to the high risk of bias, indirectness, and imprecision. Conclusions: This review provides insight into the use of echocardiograms and the frequency of test deviations in individuals with PCC. Despite existing evidence, there is a need for future studies to assess the diagnostic test accuracy of echocardiograms in PCC. Full article

Background and Objectives: The neurocognitive sequelae of COVID-19 have attracted attention as part of post-COVID condition (PCC), yet standardized tools for screening and quantifying PCC-related cognitive impairment remain scarce. The present study aimed to develop and validate the Screening for Neurocognitive Abilities Post-COVID (SNAP-COVID), a self-report questionnaire designed to capture current symptom burden and perceived changes in cognitive functioning relative to pre-COVID status in a Greek-speaking sample. Materials and Methods: Data collection occurred in three phases between August 2024 and February 2025. Dataset A (N = 27) was used for test–retest reliability. Dataset B (N = 300) was used for exploratory factor analysis (EFA), reliability testing, and convergent validity analyses with the Brain Fog Scale (BFS). Dataset C (N = 317) was used for independent validation through confirmatory factor analysis (CFA). Results: Initial EFA of the 30-item SNAP-COVID scale suggested a four-factor model, yet further item refinement yielded a robust three-factor, 24-item solution: (1) General Cognitive Functions (17 items, α = 0.948), (2) Sensory Hypersensitivity (4 items, α = 0.829), and (3) Language and Communication (3 items, α = 0.950). The total scale demonstrated excellent internal consistency (α = 0.95). Convergent validity was evident by significant correlations between SNAP impact scores and BFS scores (r = −0.442, p < 0.001). CFA confirmed the three-factor structure with acceptable fit indices (χ²(249) = 677.29, p < 0.001; CFI = 0.882; TLI = 0.869; RMSEA = 0.074; SRMR = 0.032). Conclusions: The SNAP-COVID scale is a reliable and valid instrument. Its multidimensional structure captures global and domain-specific difficulties, addressing a critical gap in post-infectious cognitive assessment. Full article

Background: Long COVID, or post-COVID-19 condition (PCC), affects around 36% of individuals following SARS-CoV-2 infection, manifesting as persistent fatigue, cognitive dysfunction, and dysautonomia among its hallmark features. Affecting an estimated 400 million individuals globally, it imposes an annual economic burden exceeding $1 trillion, yet no pharmacological therapy has demonstrated consistent efficacy in adequately powered randomized controlled trials. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a candidate intervention targeting the autonomic dysfunction and neuroinflammation responsible for PCC pathophysiology. Methods: We conducted a PRISMA 2020-compliant systematic review (PROSPERO: CRD420261287286) searching PubMed, Scopus, Cochrane, and Web of Science databases from inception to January 2026 for studies evaluating any form of VNS in adults with Long COVID. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, the JADAD scale, and the PEDro scale. Certainty of evidence was evaluated using the GRADE framework. Narrative synthesis followed SWiM guidelines. Results: Five studies (n = 154 participants) (three randomized controlled trials (RCTs) and two single-arm studies) met inclusion criteria. Three of five studies (60%) were rated high overall risk of bias; only two RCTs achieved “some concerns.” The only adequately double-blinded RCT found no significant between-group differences across all outcomes. Paradoxically, in the best-powered RCT (Percin et al.), sham stimulation produced significantly greater fatigue improvement than active taVNS, despite active taVNS producing significant HRV increases consistent with cardiac autonomic modulation. All efficacy outcomes were rated “very low” certainty (GRADE); safety was rated “low” certainty. Conclusions: Currently available evidence supporting the use of taVNS for Long COVID remains limited, and the absence of reliable target engagement markers in the included studies constrains confidence in this approach. Nonetheless, the physiological rationale remains sound, and the favorable safety profile across all included studies supports the feasibility of future investigation. However, given that positive findings were confined to inadequately controlled studies, enthusiasm for further research should be directed first toward mechanistic clarification and rigorous dose-finding work. Large-scale, double-blind, sham-controlled trials incorporating validated markers of vagal engagement are required before taVNS can be firmly recommended for COVID-19 sequelae management. Full article

Background: Cognitive difficulties are common after SARS-CoV-2 infection, yet their neurobiological underpinnings remain uncertain. Cognitive symptoms in post-COVID-19 condition (PCC) are often characterised by attentional and executive dysfunction, although the relationship between subjective symptoms and objective neurobiological changes remains uncertain. Methods: Adults previously hospitalised with COVID-19 who reported persistent cognitive symptoms underwent neuropsychological testing and 3 T MRI. The protocol included high-resolution volumetric imaging, diffusion-based tractography, and magnetic resonance spectroscopy (MRS) of frontal white matter. Data were compared with age- and sex-matched controls from a pre-COVID-19 cohort and against pooled normative MRS datasets. Analyses adjusted for intracranial volume, sex, and time since infection, with false-discovery-rate correction. This study was exploratory and hypothesis-generating in design. Results: Thirty participants were recruited; twenty-nine completed MRI acquisition. Participants (mean age 58 years; 62% female; approximately two years post-infection) demonstrated selective impairments in attention, working memory, and verbal fluency. No widespread volumetric or white-matter differences were identified, although reduced posterior hypothalamic volume and altered occipito-parietal connectivity were observed. MRS demonstrated reduced N-acetylaspartate and elevated choline, myo-inositol, and glutamate-glutamine ratios relative to normative reference ranges. No significant associations were observed between imaging measures and cognitive or symptoms outcomes after correction. Conclusions: PCC is characterised by circumscribed cognitive changes and subtle neural differences, but these objective changes do not closely align with subjective symptom severity. This mismatch shares phenotypic features with functional cognitive disorder and suggests that post-COVID-19 “brain fog” is not driven by structural or neurochemical changes alone. Instead, it potentially reflects a combination of mild neurobiological effects and functional cognitive processes. Together, these findings highlight the importance of considering both brain-based and functional contributors to persistent cognitive complaints after SARS-CoV-2 infection. Full article

Cognitive impairment is common in Post-COVID-19 Condition (PCC), yet full neuropsychological testing remains resource-intensive. Because eye movements are known to be altered in certain cognitive disorders, Eye-Tracking (ET) offers a fast, non-invasive complementary approach for large-scale screening. This study aimed to predict neuropsychological test scores of participants with PCC from ET metrics using machine and deep learning models. ET data was collected from 172 participants performing a battery of visual tasks designed to elicit smooth pursuit and fixational eye movements, as well as pupil responses to light. Cognitive performance was assessed through established neuropsychological tests. We applied regression and classification models (e.g., Random Forest, XGBoost, and deep neural networks) to predict neuropsychological performance. Models were trained using ET data alone and in combination with the Montreal Cognitive Assessment (MoCA) scores, a widely used neuropsychological test for global cognitive screening. Although predicting individual test scores was challenging, combining them into a global composite measure improved performance. Model sensitivity and specificity reached 88% and 34% using ET data alone, and 87% and 60% when integrating ET with MoCA. This last trained model outperformed the conventional MoCA, highlighting the potential of ET as a rapid screening support tool for cognitive assessment. Full article

Background: Post-COVID-19 condition (PCC) affects many survivors, with evidence of sex-specific differences in prevalence and symptom profiles. However, few prediction studies have examined whether sex-stratified models improve prediction or generalize across sexes. This study aimed primarily to develop and compare sex-stratified machine learning models for PCC prediction using routinely available baseline variables, and secondarily to assess cross-sex generalizability and adversarial robustness. Methods: We analyzed a prospective longitudinal cohort of 1006 adults hospitalized with COVID-19 at Sechenov University Hospital Network (Moscow, Russia). Demographics, smoking status, and pre-existing comorbidities were extracted from medical records, and PCC status was assessed at 6-month follow-up. Machine learning models—including classical algorithms and graph-based neural networks—were trained separately for males and females. Cross-sex validation evaluated generalizability, variable importance aided interpretation, and adversarial perturbations assessed model robustness. Results: PCC prevalence was higher in females (53.9%) than males (39.1%). Overall predictive performance was modest across all models, with AUC values ranging approximately 0.50–0.61. Graph-based models achieved the highest discrimination, with the best AUC reaching approximately 0.61, while classical approaches provided limited predictive value. Cross-sex validation showed minor asymmetry: models trained on male data performed slightly better on female cases than vice versa. Adversarial testing revealed sensitivity of all models to input perturbations. Conclusions: Demographics and comorbidities alone provide insufficient information for reliable PCC prediction. Modest sex-specific differences in model generalizability suggest distinct, sex-associated PCC phenotypes, but richer multimodal data—including clinical biomarkers, wearable-derived measures, and patient-reported outcomes—will be required to develop clinically useful and equitable predictive models. Sex-stratified approaches should be considered in future post-viral syndrome prediction studies. Full article

COVID-19 is increasingly recognized as a multisystemic disease with significant neurocognitive consequences. However, its specific impact on spatial memory, a cognitive domain essential for daily navigation and functional independence, remains insufficiently explored. This narrative review provides a critical synthesis of current evidence regarding spatial and visuospatial memory alterations across acute and post-acute phases, and post COVID-19 condition (PCC). Clinical findings, conventional and emerging assessment tools ranging from static tasks to immersive virtual reality environments, as well as potential neurobiological mechanisms, were considered. Results suggested that spatial memory is frequently compromised after COVID-19 disease, with deficits being most pronounced at longer retention intervals and within navigational contexts. Neuroimaging and biomarker data further reveal selective vulnerability in the medial temporal lobe, characterized by hippocampal atrophy, hypoperfusion, and disrupted functional connectivity. Importantly, traditional neuropsychological tools may underestimate these impairments due to limited ecological validity. Therefore, implementing multimodal assessment frameworks that integrate navigational paradigms is essential to enhance diagnostic sensitivity and facilitate the development of targeted rehabilitation strategies for PCC patients. Full article

Background/Objectives: Post-COVID-19 condition (PCC) remains poorly characterized beyond two years, particularly among intensive care unit (ICU) survivors. We aimed to describe the prevalence, persistence, and late consequences of PCC up to 32 months after discharge in an ICU cohort. Methods: This single-center longitudinal cohort included 170 adults with confirmed SARS-CoV-2 infection admitted to an ICU in Cáceres (Spain) between March 2020 and March 2021. 94 survivors entered follow-up at discharge and 3, 6, 12, 18, 24, and 32 months. PCC manifestations were grouped into five organ system domains (respiratory, cardiovascular, renal, infectious, and musculoskeletal/neuromuscular) and recorded only when supported by clinician-confirmed diagnoses or diagnostic tests. Prevalence at each visit, persistence, and new onset of manifestations between 3 and 6 months, and the cumulative incidence of new chronic diseases between 18 and 32 months were estimated with 95% confidence intervals. Results: Any PCC manifestation was almost universal at discharge (96.8% [95% CI, 91.1–98.9]) and remained high at 12 months (85.2% [95% CI, 76.3–91.2]), declining to 48.6% at 24 months and 25.7% at 32 months. Respiratory manifestations predominated early and were largely resolved by 32 months, whereas musculoskeletal/neuromuscular involvement remained relatively stable. From 18 to 32 months, 36.5% (95% CI, 26.4–47.9) of survivors developed at least one chronic condition, most frequently cardiovascular disease (14.9% [95% CI, 8.5–24.7]). Conclusions: Long-term PCC manifestations and incident chronic diseases are common among ICU COVID-19 survivors, underscoring the need for prolonged follow-up and post-ICU care. Full article

Background/Objectives: This study aimed to determine the prevalence of persistent symptoms and the radiological and laboratory evolution at 6 months and 5 years after discharge in patients hospitalized for SARS-CoV-2 pneumonia during the first wave of the pandemic in Spain and to estimate the healthcare impact of their follow-up. Methods: A retrospective longitudinal observational study was conducted at the “Hospital Central de la Defensa”. A total of 200 patients aged >18 years with a diagnosis of SARS-CoV-2 pneumonia were screened. Clinical, radiological, and laboratory data were collected from electronic medical records. Patients with symptoms or radiological abnormalities at discharge underwent in-person evaluations, while the remainder were assessed by telephone. Results: A total of 182 patients met the inclusion and exclusion criteria. Of these, 112 were assessed in the outpatient setting; 60.7% required in-person evaluations, with normal pulmonary auscultation in 93.6%, complete radiological resolution in 85%, and normalized laboratory parameters in almost all cases. At 6 months, 26.5% presented at least one residual symptom, whereas only three patients (4.5%) reported symptoms at 5 years. No risk factors associated with symptom persistence were identified. The estimated cumulative healthcare cost was EUR 21,627.50. Conclusions: Among patients hospitalized for SARS-CoV-2 pneumonia during the first wave of the pandemic, 26.7% and 4.46% presented at least one persistent symptom at 6 months and 5 years after discharge, respectively. Full article

Background: Persistent low-grade inflammation has been proposed as part of the biological mechanisms underlying post-COVID condition (PCC), which can result in laboratory tests abnormalities. However, the accuracy of routine laboratory tests for the diagnosis and follow-up of PCC is still under discussion. Methods: Patients with SARS-CoV-2 infection enrolled in the prospective, multinational ORCHESTRA cohort study, which included both European and non-European countries, were followed up for 18 months after acute infection. Blood test results were collected at acute infection and at 6, 12, and 18 months. A multivariable analysis was performed to estimate the relationship between the alterations of biochemical markers and the presence of four distinct PCC phenotypes, identified previously through a principal component analysis—respiratory (RESc), chronic pain (CPc), chronic fatigue (CFc), and neurosensorial (NSc)—during follow-up. Furthermore, this study investigated the correlation between biochemical parameters measured during the acute phase and the subsequent development of PCC. Finally, the relationship between the severity of the acute infection and biochemical abnormalities observed during follow-up was assessed. Results: The cohort included 4587 patients, 58% male, with a mean age of 58.7 (±15.5) years. A robust multivariable analysis demonstrated that, compared to controls, patients with PCC, and in particular those in the RESc cluster, presented higher mean C-reactive protein (CRP) levels at the 12- and 18-month follow-up (p-value = 0.01). In each follow-up, CRP values in patients with PCC and RESc were above 3 mg/L, corresponding to those observed in low-grade inflammation (3–10 mg/L). The severity of COVID-19 acute infection was associated with increased levels of CRP, ferritin and LDH during follow-up (p < 0.001). Biochemistry abnormalities detected during the early stages of acute COVID-19 did not correlate with an increased risk of developing PCC and its phenotypes. Conclusions: In patients with the RESc PCC phenotype, identified through a principal component analysis, blood test abnormalities consistent with prolonged and sustained low-grade inflammation can be detected up to 18 months after acute infection, supporting its role in the pathogenesis of PCC. Based on these results, trials on anti-inflammatory drugs, together with symptom-tailored interventions for patients with RESc, should be planned to prove their effectiveness in managing PCC and improving patient outcomes. Full article