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Search Results (1,006)

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Keywords = post-COVID syndrome

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24 pages, 2245 KB  
Article
Haptoglobin Phenotypes Stratify Post-Exertional Cognitive Dysfunction Associated with Altered Cerebral Oxygenation and Metabolic Signatures in Long COVID
by Atefeh Moezzi, Wesam Elremaly, Corinne Leveau, Anita Franco, Oleg Nepotchatykh, Christopher W. Armstrong and Alain Moreau
Int. J. Mol. Sci. 2026, 27(15), 7000; https://doi.org/10.3390/ijms27157000 - 4 Aug 2026
Abstract
Long COVID (LC) is a heterogeneous post-infectious syndrome characterized by persistent symptoms, yet the biological basis underlying its interindividual variability remains poorly understood. Given the clinical overlap between LC and myalgic encephalomyelitis (ME), and prior demonstration that haptoglobin (Hp) phenotypes modulate symptom severity [...] Read more.
Long COVID (LC) is a heterogeneous post-infectious syndrome characterized by persistent symptoms, yet the biological basis underlying its interindividual variability remains poorly understood. Given the clinical overlap between LC and myalgic encephalomyelitis (ME), and prior demonstration that haptoglobin (Hp) phenotypes modulate symptom severity in ME, we investigated whether Hp phenotypes similarly stratify post-exertional cognitive dysfunction in LC. In this longitudinal observational study, 44 individuals with LC and 20 short-course COVID controls, who recovered rapidly from SARS-CoV-2 infection without persistent symptoms or sequelae, underwent Hp phenotyping alongside metabolomic and physiological profiling before and after a standardized 90 min passive post-exertional challenge. Hp phenotypes identified clinically distinct LC subgroups. Compared with Hp1-1 individuals, Hp2 allele carriers exhibited greater fatigue, poorer physical function, and more severe post-exertional symptoms. Immediately following the challenge, Hp2-2 participants with LC showed significant cognitive decline, whereas Hp1-1 individuals demonstrated cognitive resilience and more favorable longitudinal cognitive trajectories. This differential susceptibility was accompanied by higher post-exertional cerebral fractional tissue oxygen extraction in the right hemisphere in Hp1-1 individuals and by distinct metabolic signatures, with Hp2 allele carriers exhibiting lower post-exertional plasma concentrations of citric acid, isethionate, and glucosamine. Lower metabolite levels were associated with poorer cognitive performance. These findings support Hp phenotypes as promising candidate biomarkers for biological stratification in Long COVID, pending validation in larger independent cohorts. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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32 pages, 759 KB  
Systematic Review
The Impact of Pulmonary Rehabilitation in Patients with Post-COVID-19 Syndrome: A Systematic Review
by Vlad-Florin Oiegar, Cristina Călărașu, Paraschiva Postolache, Constantin Ghimuș, Mara-Amalia Bălteanu, Simona Pătru, Dănuț Caimac, Ana Maria Bumbea, Simona-Maria Roșu and Ionela Alina Croitoru
Med. Sci. 2026, 14(4), 443; https://doi.org/10.3390/medsci14040443 - 27 Jul 2026
Viewed by 185
Abstract
Background: Post-COVID-19 syndrome represents a global health problem, manifesting with persistent multiple organ symptoms, including respiratory ones. This review aimed to evaluate the efficacy of different pulmonary rehabilitation interventions in the management of the disease, including its particularities. Methods: This systematic review was [...] Read more.
Background: Post-COVID-19 syndrome represents a global health problem, manifesting with persistent multiple organ symptoms, including respiratory ones. This review aimed to evaluate the efficacy of different pulmonary rehabilitation interventions in the management of the disease, including its particularities. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement and prospectively registered in the PROSPERO database (CRD420261292824). PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 2021 to January 2026. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Cochrane Risk of Bias 2 (RoB 2) tool. Twenty randomized controlled trials involving 2101 adult patients with post-COVID-19 syndrome met the eligibility criteria and were included in the qualitative synthesis. Results: Pulmonary rehabilitation (PR) demonstrated significant improvements in exercise capacity, with notable increases in 6MWT and VO2max. Respiratory and peripheral muscle strength significantly increased. The quality of life, dyspnea and fatigue consistently improved. The results for intrinsic pulmonary function, anxiety, and depression were heterogeneous, suggesting benefits more related to reconditioning. Conclusions: Pulmonary rehabilitation is an essential and efficient component in post-COVID-19 syndrome, improving physical function, respiratory and peripheral muscle strength, the quality of life, fatigue and dyspnea. Telerehabilitation is a viable alternative. Adapting protocols is crucial, recognizing that most benefits derive from physical reconditioning and muscle training, not necessarily from major structural pulmonary changes. Full article
(This article belongs to the Section Pneumology and Respiratory Diseases)
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17 pages, 1324 KB  
Article
Phenotypic Evolution, Clinical Subtypes, and Independent Predictors of Long COVID: A Retrospective Cohort Study
by Lanre Peter Daodu, Yogini Raste, Judith E. Allgrove, Francesca I. F. Arrigoni and Reem Kayyali
Biomedicines 2026, 14(8), 1662; https://doi.org/10.3390/biomedicines14081662 - 24 Jul 2026
Viewed by 452
Abstract
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 [...] Read more.
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
(This article belongs to the Section Molecular and Translational Medicine)
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11 pages, 563 KB  
Article
Reliability and Validity of the Simple Qi Deficiency Score in Patients with Post-COVID-19 Condition
by Kazuki Tokumasu, Yoshifumi Sugiyama, Yuki Otsuka, Yohei Masuda, Nobuyoshi Matsuki, Keigo Ueda and Fumio Otsuka
Medicina 2026, 62(7), 1421; https://doi.org/10.3390/medicina62071421 - 22 Jul 2026
Viewed by 254
Abstract
Background and Objectives: Persistent COVID-19 sequelae, often referred to as “long COVID”, still constitute a major global medical challenge. In particular, general fatigue is the most widely reported, serious symptom. In the framework of Japanese traditional (Kampo) medicine (JTM), post-infection fatigue is frequently [...] Read more.
Background and Objectives: Persistent COVID-19 sequelae, often referred to as “long COVID”, still constitute a major global medical challenge. In particular, general fatigue is the most widely reported, serious symptom. In the framework of Japanese traditional (Kampo) medicine (JTM), post-infection fatigue is frequently considered a “Qi deficiency”, a significant loss of vital energy. In JTM, accurately diagnosing Qi deficiency is essential for determining the appropriate treatment. However, one challenge in JTM diagnosis is that mastering traditional diagnostic techniques takes time. We sought to validate the “Qi deficiency score”, a quantitative patient-reported outcome measure designed to assess Qi deficiency in patients suffering from long COVID. Materials and Methods: This was a methodological study. We conducted a cross-sectional study of 237 patients who sought treatment at the post-COVID-19 clinic (COVID-19 Aftercare Clinic) at Okayama University Hospital. The patient population was randomly split into two cohorts: one for Exploratory Factor Analysis (EFA, n = 122) and another for Confirmatory Factor Analysis (CFA, n = 115). The simple Qi-deficiency score comprises eight items derived from Terasawa’s diagnostic criteria, with a total range of 0–56. We evaluated internal consistency using Cronbach’s α/McDonald’s ω and examined structural validity. Convergent validity was established by examining correlations between the simple Qi deficiency score and the Fatigue Assessment Scale (FAS), the Self-rating Depression Scale (SDS), and Quality of Life (QOL) metric. Results: The score’s internal consistency (α = 0.64 and ω = 0.63) was considered modest for screening traditional clinical syndromes. EFA showed major factors representing Qi deficiency symptoms. CFA supported a one-factor model with modest fit indices (CFI = 0.87; RMSEA = 0.079; SRMR = 0.077; TLI = 0.82). Factor loadings revealed that “Body feels tired (now)” (0.98) and “Tires easily (tendency)” (0.73) were the most significant symptoms. Convergent validity showed a strong positive correlation with the FAS (r = 0.61, ρ = 0.60) and a moderate correlation with the SDS (r = 0.55, ρ = 0.55). A significant negative correlation was found with QOL scores (r = −0.42, ρ = −0.43). Conclusions: The simple Qi deficiency score may be useful for evaluating Qi deficiency in patients with post-COVID-19 condition. Full article
(This article belongs to the Special Issue The Burden of COVID-19 Pandemic on Mental Health, 2nd Edition)
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17 pages, 808 KB  
Article
Dietary Vitamin Intake and Central and Peripheral Arterial Stiffness in Patients with Long COVID: The BioICOPER Study
by David Arjol, Silvia Arroyo-Romero, Elena Navarro-Matías, Alicia Navarro-Cáceres, Nuria Suárez-Moreno, Andrea Domínguez-Martín, Manuel A. Gómez-Marcos, Marta Gómez-Sánchez, Leticia Gómez-Sánchez and BioICOPER Investigators Group
Nutrients 2026, 18(14), 2336; https://doi.org/10.3390/nu18142336 - 16 Jul 2026
Viewed by 271
Abstract
Background: Long COVID (LC) has been associated with persistent inflammation and endothelial dysfunction. Dietary components, particularly vitamins, are involved in inflammation, oxidative stress, and vascular homeostasis, and may influence arterial stiffness in this population. However, the relationship between dietary vitamin intake and [...] Read more.
Background: Long COVID (LC) has been associated with persistent inflammation and endothelial dysfunction. Dietary components, particularly vitamins, are involved in inflammation, oxidative stress, and vascular homeostasis, and may influence arterial stiffness in this population. However, the relationship between dietary vitamin intake and vascular stiffness parameters in patients with LC remains poorly understood. Objective: To analyze the association between dietary vitamin intake and central and peripheral arterial stiffness, evaluated by carotid–femoral pulse wave velocity (cfPWV) and brachial–ankle pulse wave velocity (baPWV), in patients with LC. Methods: We conducted a cross-sectional study that included 304 patients with LC. Dietary vitamin intake was assessed using a validated 7-day dietary record (EVIDENT tool). Vascular assessment included cfPWV and baPWV, measured using validated devices (SphygmoCor® and VaSera®). Multiple linear regression analyses were performed to evaluate the associations between vitamin intake and vascular parameters. Model 1 was adjusted for age and sex, while Model 2 additionally included the number of metabolic syndrome components, the SF-36 general health domain, and adherence to the Mediterranean diet. Correction for multiple comparisons was performed using the Benjamini–Hochberg procedure across 36 vitamin–outcome–model contrasts. Results: The mean age was 52.78 ± 11.91 years, and 207 participants were women (68.1%); men were older than women (p = 0.004). In multiple regression analysis, inverse estimates for vitamin B1 intake with cfPWV were observed in both Model 1 (β = −0.568; 95% CI: −1.016 to −0.119; p = 0.014) and Model 2 (β = −0.491; 95% CI: −0.923 to −0.059; p = 0.027). Vitamin B6 intake showed a similar pattern with cfPWV in Model 1 (β = −0.312; 95% CI: −0.606 to −0.018; p = 0.039) and Model 2 (β = −0.302; 95% CI: −0.586 to −0.018; p = 0.038). Vitamin B2 showed inverse but non-significant associations with cfPWV. No significant associations were observed between vitamin intake and baPWV. After FDR correction, no vitamin-arterial stiffness association remained statistically significant; the FDR-adjusted q-value for the B1/B6-cfPWV estimates was 0.347. Conclusions: In this exploratory cross-sectional study, habitual food-based vitamin intake was not significantly associated with central or peripheral arterial stiffness after correction for multiple comparisons. Vitamins B1 and B6 showed inverse nominal estimates with cfPWV; however, these estimates did not survive FDR correction and were not reproduced for baPWV. Longitudinal studies incorporating biochemical micronutrient markers, medication and supplementation data, inflammatory and homocysteine-related biomarkers, and repeated vascular assessment are needed to clarify whether vitamin status is related to vascular health among individuals with persistent post-COVID-19 symptoms. Full article
(This article belongs to the Special Issue Vitamins and Human Health: 3rd Edition)
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18 pages, 949 KB  
Article
Cardiovascular and Multisystem Outcomes Identified at Short- and Long-Term Follow-Up After COVID-19 Hospitalization: A Retrospective Cohort Study
by Sofia Teodora Muntean, Andreea-Raluca Cozac-Szoke, Andreea Cătălina Tinca, Diana Maria Chiorean, Adrian Horațiu Sabău, Iuliu Gabriel Cocuz, Raluca Niculescu, Claudia Raluca Mariean, Nadja Emily Pop, Ovidiu Simion Cotoi and Anca Ileana Sin
COVID 2026, 6(7), 124; https://doi.org/10.3390/covid6070124 - 16 Jul 2026
Viewed by 269
Abstract
Background: Persistent cardiovascular and multisystem manifestations remain an important concern following hospitalization for coronavirus disease 2019 (COVID-19). However, the spectrum of newly identified conditions during follow-up and their relationship with acute disease severity remain incompletely characterized. This study aimed to describe cardiovascular and [...] Read more.
Background: Persistent cardiovascular and multisystem manifestations remain an important concern following hospitalization for coronavirus disease 2019 (COVID-19). However, the spectrum of newly identified conditions during follow-up and their relationship with acute disease severity remain incompletely characterized. This study aimed to describe cardiovascular and multisystem diagnoses, identified during short-term and long-term follow-up and to evaluate the association between acute-phase clinical characteristics, biomarkers, and subsequent outcomes. Methods: We conducted a retrospective observational cohort study including 762 adults hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between January 2021 and December 2022. Follow-up data were obtained from patients who re-presented to the same hospital during short-term follow-up (mean 4.33 months; n = 130) or long-term follow-up (mean 2.06 years; n = 186). Newly documented cardiovascular and non-cardiovascular diagnoses recorded during routine clinical care were analyzed separately for each follow-up cohort. Multivariable logistic regression was used to identify predictors of in-hospital mortality and cardiovascular outcomes. Results: At least one newly documented diagnosis was identified in 120/130 patients (92.3%) during short-term follow-up and in 175/186 patients (94.1%) during long-term follow-up. Cardiovascular diagnoses were identified in 32.3% and 45.2% of patients attending short-term and long-term follow-up, respectively. Hypertension and atherosclerosis were the most frequent cardiovascular diagnoses during short-term follow-up, whereas heart failure and ischemic heart disease predominated among patients attending long-term follow-up. Pulmonary fibrosis was the most common non-cardiovascular diagnosis at both follow-up periods. Elevated D-dimer and fibrinogen levels during acute COVID-19 were independently associated with in-hospital mortality, whereas acute-phase NT-proBNP was not independently associated with cardiovascular diagnoses identified during follow-up. Conclusions: Patients who re-presented for clinical evaluation after hospitalization for COVID-19 exhibited a substantial burden of newly documented cardiovascular and multisystem diagnoses. Given the retrospective design, independent follow-up cohorts, and absence of a non-COVID control group, these findings should be interpreted as observational post-hospitalization data rather than evidence of causal or progressive post-COVID-19 disease. Prospective controlled longitudinal studies are needed to better define the long-term health consequences of SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Exploring the Multisystem Features of Long COVID)
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15 pages, 818 KB  
Article
Evolutionary Predictors of Post-COVID Syndrome
by Maria Luisa Asensio Tomás, Philip Erick Wikman-Jorgensen, Jose Antonio Quesada-Rico, José Miguel Seguí-Ripoll, Vicente Gil-Guillén and Vicente Giner-Galvañ
J. Clin. Med. 2026, 15(14), 5550; https://doi.org/10.3390/jcm15145550 - 15 Jul 2026
Viewed by 246
Abstract
Objectives: To analyze evolutionary predictors of post-COVID syndrome (PCS). Methods: This Cohort study was conducted from April 2021 to December 2023. PCS persistence was defined as a score of ≥2 points on the post-COVID-19 Functional Status (PCFS) scale (range 0–4, where [...] Read more.
Objectives: To analyze evolutionary predictors of post-COVID syndrome (PCS). Methods: This Cohort study was conducted from April 2021 to December 2023. PCS persistence was defined as a score of ≥2 points on the post-COVID-19 Functional Status (PCFS) scale (range 0–4, where higher scores indicate more limitations). Symptom clusters were identified using correspondence analysis. The association between PCS persistence and symptoms and symptom clusters were assessed using multivariable analysis, considering both the acute infection period and the baseline PCS visit variables. Results: The 112 included patients showed a mean of 6.1 symptoms (standard deviation [SD] 3.2), most commonly dyspnea (67.9%), asthenia (67.0%), fatigue (57.1%), and myalgia (49.1%). Regarding baseline functional status, 59.8% scored 2 points on the PCFS; 40.2%, 3 points; and 2.6%, 4 points. Moreover, 68.7% had depression and 83.0%, anxiety. Two symptom clusters emerged: anxiety + depression + severe PCFS, and palpitations + hyporexia + dyspnea. At a mean of 12.1 months (SD 9.2), the persistence rate was 33.9% (cumulative persistence time 20 months [SD 11.9]). Persistence was significantly associated with the absence of rhinitis (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.28–10.52) during acute infection, and the presence of fatigue (OR 4.88, 95% CI 1.77–13.44) and depression (moderate: OR 4.28, 95% CI 1.05–17.44; severe: OR 10.31, 95% CI 2.60–40.90) at the baseline visit. The model multivariable demonstrated a good fit (likelihood ratio test 30.1, p < 0.001) and predictive capacity (area under the receiver operating curve 0.804). The anxiety + depression + severe PCFS cluster was significantly associated with persistence (OR 3.26, 95% CI 1.21–8.76; p = 0.012). Conclusions: A third of patients with PCS still experience significant functional impairment 20 months after onset. Persistence is associated with the absence of rhinitis during acute infection and with severe anxiety, depression, and functional impairment measured by the PCFS on detection of PCS. Full article
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15 pages, 455 KB  
Article
Post-Acute COVID-19 Symptoms Clusters and Work Status
by Aoyjai Prapanjaroensin Montgomery, Nathaniel Erdmann, Wanda Hall, Juan Pablo Pilco and Emily B. Levitan
Occup. Health 2026, 1(3), 31; https://doi.org/10.3390/occuphealth1030031 - 15 Jul 2026
Viewed by 499
Abstract
Long COVID affects an estimated 10–20% of SARS-CoV-2 survivors with heterogeneous, multi-system symptoms persisting for months to years, contributing to significant workforce disruption and reduced functional capacity. This exploratory study identified symptom clusters following SARS-CoV-2 infection, examined associated personal and clinical characteristics, and [...] Read more.
Long COVID affects an estimated 10–20% of SARS-CoV-2 survivors with heterogeneous, multi-system symptoms persisting for months to years, contributing to significant workforce disruption and reduced functional capacity. This exploratory study identified symptom clusters following SARS-CoV-2 infection, examined associated personal and clinical characteristics, and assessed work status across clusters. Among 273 individuals from a single clinical site, we used baseline surveys to capture long COVID symptoms and 2-week follow-up surveys to assess work status, and applied K-means clustering to identify symptom groupings. Three preliminary clusters emerged: Cluster 1 (“brain fog”), characterized by fatigue (96%), difficulty remembering (97%), and difficulty concentrating (94%); Cluster 2 (“undifferentiated”), with low prevalence across all symptoms; and Cluster 3 (“persistent acute”), marked by cough (92%), congestion (80%), headaches (78%), and body aches (78%). Notably, among Cluster 1 (“brain fog”) respondents, 44% reported not working, and approximately half attributed their work absence to COVID-related symptoms. These hypothesis-generating findings suggest that neurocognitive symptom clusters may be associated with greater work absence in some individuals, though the small number of respondents limits firm conclusions. The findings suggest that targeted occupational rehabilitation strategies may warrant further investigation as potential strategies for individuals experiencing post-infectious cognitive impairment following SARS-CoV-2 infection. Full article
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14 pages, 251 KB  
Article
Musculoskeletal Pain and Neuropathic Pain Features Among Individuals with Long COVID and a History of Pain: Characteristics and Impact on Health-Related Quality of Life
by Adam B. Smith, Philip G. Conaghan, Christine Comer, Manoj Sivan and Sarah R. Kingsbury
COVID 2026, 6(7), 118; https://doi.org/10.3390/covid6070118 - 7 Jul 2026
Viewed by 300
Abstract
Background: Post-COVID-19 syndrome or Long COVID (LC) is a multi-system condition characterised by persistent symptoms beyond three months following SARS-CoV-2 infection. Pain, particularly musculoskeletal and neuropathic pain, is commonly reported and may substantially affect functioning and health-related quality of life (HRQoL). However, there [...] Read more.
Background: Post-COVID-19 syndrome or Long COVID (LC) is a multi-system condition characterised by persistent symptoms beyond three months following SARS-CoV-2 infection. Pain, particularly musculoskeletal and neuropathic pain, is commonly reported and may substantially affect functioning and health-related quality of life (HRQoL). However, there is limited detailed characterisation of pain phenotypes and their differential impact on outcomes in LC. This study aimed to (i) characterise pain associated with LC, (ii) identify factors associated with pain type and severity, and (iii) examine its impact on HRQoL, physical activity, and work. Methods: A cross-sectional survey was conducted among adults with clinician-diagnosed or self-reported LC who reported current or previous joint, muscle, or nerve pain. Participants completed validated patient-reported outcome measures including the C19-YRS, Nordic Musculoskeletal Questionnaire, Pain Detect Questionnaire (PD-Q), Musculoskeletal Health Questionnaire, and EQ-5D-5L. Participants were classified into neuropathic, nociceptive, or ambiguous pain groups based on PD-Q scores. Descriptive analyses, group comparisons, and backward stepwise ordinary least squares regression were used to examine factors associated with overall pain (PD-Q Total). Results: Among 198 participants (73% female; mean age 52 ± 12.7 years; mean LC duration 2.4 years), 96% reported new or worsened pain following COVID-19 infection, with muscle pain (87%), joint pain (84%), and nerve pain (66%) most frequently reported. PD-Q scores suggestive of neuropathic pain were identified in 28% of participants and were associated with significantly greater pain intensity, symptom burden, functional impairment, and lower HRQoL (p < 0.05). These participants reported higher average pain scores across all body regions and greater radiating pain (76%) compared to other groups. Functional disability and anxiety were significant factors associated with pain severity. Conclusions: Pain is highly prevalent in LC, with neuropathic pain representing a distinct and more severe phenotype associated with substantial functional and quality-of-life impacts. This study provides novel comparative evidence on pain phenotypes and their differential burden, highlighting the need for targeted pain assessment and management strategies in LC. Full article
(This article belongs to the Section COVID Clinical Manifestations and Management)
41 pages, 2622 KB  
Review
Folic Acid and Endothelial Dysfunction in COVID-19
by Maria Macarena Massip Copiz
Life 2026, 16(7), 1116; https://doi.org/10.3390/life16071116 - 4 Jul 2026
Viewed by 689
Abstract
Since 2020, recurrent waves of SARS-CoV-2 infection have persisted globally. Despite the advancements in vaccines and pharmacological treatments, a subset of patients still exhibits an aggressive form of COVID-19 requiring prolonged stays in the intensive care unit (ICU) or experiences major acute infections [...] Read more.
Since 2020, recurrent waves of SARS-CoV-2 infection have persisted globally. Despite the advancements in vaccines and pharmacological treatments, a subset of patients still exhibits an aggressive form of COVID-19 requiring prolonged stays in the intensive care unit (ICU) or experiences major acute infections (or reinfections) and long-term symptoms. Endothelial dysfunction is one of the key events contributing to both the severity of acute COVID-19 and the development of long COVID (LC)/post-acute sequelae of SARS-CoV-2 infection (PASC) syndrome. Since the beginning of the pandemic, the efficacy of nutraceuticals, particularly essential micronutrients, has been investigated as a complementary treatment to prevent disease onset and improve clinical outcomes. One such bioactive molecule is folate (vitamin B9), a member of the B-vitamin family involved in the pathogenesis of multiple diseases, including viral infections and vascular disorders. This review examines the role of folic acid in COVID-19 and its interaction with homocysteine metabolism, which is frequently dysregulated in inflammatory endothelial diseases. It further discusses the potential benefits of folic acid supplementation for the prevention and treatment of COVID-19 in both the acute and long-term phases of the disease, alongside the therapeutic role of vitamin B12 supplementation in LC syndrome. Full article
(This article belongs to the Section Physiology and Pathology)
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22 pages, 629 KB  
Article
Characterising Pain in Post-COVID-19 Syndrome: An Observational Study of Intensity and Sensitivity
by Laura Pérez-Gisbert, Gregory Reychler, Beatriz Brea-Gómez, Concepción Morales-García, Marie C. Valenza and Irene Torres-Sánchez
Diagnostics 2026, 16(13), 2023; https://doi.org/10.3390/diagnostics16132023 - 29 Jun 2026
Viewed by 313
Abstract
Background/Objectives: Post-COVID-19 syndrome (PCS) is frequently accompanied by pain, which may coexist with alterations in multiple health domains. However, pain in PCS has rarely been explored from a multidimensional approach combining subjective and objective measures. Objective: To describe pain in subjects with [...] Read more.
Background/Objectives: Post-COVID-19 syndrome (PCS) is frequently accompanied by pain, which may coexist with alterations in multiple health domains. However, pain in PCS has rarely been explored from a multidimensional approach combining subjective and objective measures. Objective: To describe pain in subjects with PCS using pain intensity and the pressure pain threshold (PPT), and to examine the associations between these measures and descriptive characteristics as well as health status. Methods: A cross-sectional observational study was conducted in 45 previously hospitalised adults with PCS. Pain intensity was assessed using the visual analogue scale and PPT was assessed by algometry. Health status included fatigue, dyspnoea, anxiety, depression, quality of life, functionality, frailty, physical activity, muscle quality, muscle strength, physical performance, and functional capacity. Analyses were conducted using SPSS v30.0. Results: Participants showed moderate pain intensity and variability in PPT, with a significant inverse association between both measures. Bivariate analyses showed that higher pain intensity and lower PPT were associated with worse physical, psychological, and functional outcomes. In regression analyses, pain intensity was associated with sex, length of hospital stay, PPT, and quality of life; PPT was associated with sex, pain intensity, and grip strength. Model explanatory capacity varied, and some models were not statistically significant. Conclusions: Subjects with PCS exhibited moderate pain intensity and variability in pain sensitivity, with an association between subjective and objective pain measures. Pain measures were associated with multiple health domains at the bivariate level, while regression analyses identified a limited number of associations with variable explanatory capacity. These findings support comprehensive pain assessment in PCS. Full article
(This article belongs to the Special Issue Advances in Pain Medicine: Diagnostic and Management Innovations)
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15 pages, 1037 KB  
Article
Anxiety-Depressive Disorders in 200 Patients with Post-COVID-19 Syndrome: Prevalence and Predictors from a Cross-Sectional Study
by Sylwia Drzymała, Anna Blask-Osipa, Anna Szczepańska-Alvarez, Hanna Markowska, Małgorzata Dobrzyńska, Sławomira Drzymała-Czyż and Jarosław Walkowiak
Medicina 2026, 62(7), 1234; https://doi.org/10.3390/medicina62071234 - 26 Jun 2026
Viewed by 371
Abstract
Background and Objectives: Recovering from COVID-19 does not always imply a full return to health and may lead to the development of post-COVID-19 syndrome. Post-COVID-19 manifestations include, among others, symptoms of depression and/or anxiety. The aim of the study was to assess [...] Read more.
Background and Objectives: Recovering from COVID-19 does not always imply a full return to health and may lead to the development of post-COVID-19 syndrome. Post-COVID-19 manifestations include, among others, symptoms of depression and/or anxiety. The aim of the study was to assess the prevalence of anxiety and depressive disorders and to identify their exogenous and endogenous predictors in individuals with post-COVID-19 syndrome. Materials and Methods: The study included 200 participants (116 women and 84 men, aged 18–80) diagnosed with post-COVID-19 syndrome. Participants completed psychological assessments, including the Hospital Anxiety and Depression Scale (HADS), the Generalized Anxiety Disorder 7 (GAD-7), and the Beck Depression Inventory (BDI). Comorbidities were also evaluated. Results: Based on the HADS, anxiety was identified in 41.5% of respondents and depression in 39.5%. Generalized anxiety disorder was screened positive for 36.5% of respondents (GAD-7), while mild depression was observed in 37.0% (BDI). Among participants with post-COVID-19 syndrome and diabetes, the risk of developing depression was three times higher than in individuals without comorbidities. In smoking women with post-COVID-19 syndrome and diabetes, the risk of developing depressive disorders was estimated to exceed 90%. Conclusions: The risk of developing anxiety and depressive disorders in individuals with post-COVID-19 syndrome and multimorbidity is very high, highlighting the need for preventive psychological care, including targeted screening programs, for those at greatest risk. Full article
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28 pages, 945 KB  
Article
β-Cell Dysfunction and Altered Thyroid Hormone Dynamics in Post-COVID Metabolic Disturbances: An Immunometabolic Cross-Sectional Study
by Victoria Tsvetkova, Malvina Todorova, Milena Atanasova, Irena Gencheva and Katya Todorova
Biomedicines 2026, 14(7), 1420; https://doi.org/10.3390/biomedicines14071420 - 23 Jun 2026
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Abstract
Background: SARS-CoV-2 infection has been associated with metabolic disturbances and endocrine alterations, including effects on pancreatic β-cell function and thyroid hormone regulation. However, the relationship between thyroid function and β-cell compensatory capacity in the post-COVID state remains unclear. Methods: In this [...] Read more.
Background: SARS-CoV-2 infection has been associated with metabolic disturbances and endocrine alterations, including effects on pancreatic β-cell function and thyroid hormone regulation. However, the relationship between thyroid function and β-cell compensatory capacity in the post-COVID state remains unclear. Methods: In this cross-sectional study, we evaluated β-cell compensation (HOMA-B/HOMA-IR) and thyroid parameters in three groups: patients with active COVID-19, individuals with post-COVID metabolic disturbances, and a COVID-negative metabolic syndrome reference group. Thyroid status was assessed using both comprehensive clinical classification and biochemical criteria. Associations between thyroid hormones and β-cell function were analyzed using Spearman correlation. Results: β-cell compensatory capacity differed significantly across groups, with the lowest values observed during active COVID-19 and intermediate impairment in the post-COVID cohort compared with the metabolic syndrome group. FT3 concentrations and the FT3/FT4 ratio were significantly reduced during active infection and were positively associated with β-cell compensation in the post-COVID group (ρ = 0.421, p = 0.018 and ρ = 0.382, p = 0.031, respectively). Although thyroid dysfunction appeared more prevalent in the post-COVID cohort when defined by overall clinical classification, no significant differences were observed when thyroid status was evaluated based solely on biochemical criteria, excluding clinical history and euthyroid sick syndrome. Conclusions: Post-COVID metabolic disturbances are characterized by impaired β-cell compensatory capacity and alterations in peripheral thyroid hormone dynamics. The apparent increase in thyroid dysfunction is largely driven by pre-existing thyroid disease and non-thyroidal illness effects rather than intrinsic thyroid pathology. These findings are consistent with the hypothesis of a potential post-COVID immunometabolic phenotype involving both pancreatic and thyroid-related mechanisms. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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10 pages, 455 KB  
Brief Report
Fasciculations Following COVID-19 Vaccination—A Case Series of Ten Patients
by Ameli Breuer, Vanessa Raeder, Helena Franziska Pernice, Fabian Boesl, Harald Prüss, Heinrich Audebert, Katrin Hahn and Christiana Franke
Vaccines 2026, 14(6), 541; https://doi.org/10.3390/vaccines14060541 - 19 Jun 2026
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Abstract
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 [...] Read more.
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
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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11 pages, 864 KB  
Article
Pneumococcal Detection and Bacterial Co-Detection in Children After COVID-19: A Two-Year Multiplex PCR Study
by Loredana Stavăr-Matei, Lavinia Țocu, Aurel Nechita, Luiza Camelia Nechita, Oana Mariana Mihailov, Florentin Dimofte and George Țocu
Biomedicines 2026, 14(6), 1381; https://doi.org/10.3390/biomedicines14061381 - 18 Jun 2026
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Abstract
Background: Non-pharmaceutical interventions during the COVID-19 pandemic altered respiratory pathogen circulation, and a bacterial rebound followed once restrictions were lifted. We describe pediatric pneumococcal respiratory infections and their bacterial co-detections in the immediate post-pandemic period. Methods: We retrospectively analyzed respiratory specimens [...] Read more.
Background: Non-pharmaceutical interventions during the COVID-19 pandemic altered respiratory pathogen circulation, and a bacterial rebound followed once restrictions were lifted. We describe pediatric pneumococcal respiratory infections and their bacterial co-detections in the immediate post-pandemic period. Methods: We retrospectively analyzed respiratory specimens from children aged 0–18 years tested with a multiplex real-time PCR panel (Allplex Respiratory Panel, Seegene, Seoul, South Korea; seven bacterial pathogens) restricted to this predefined bacterial spectrum at a tertiary pediatric hospital in Galați, Romania, during 2022 and 2023. A total of 2546 panels were performed in 2022 and 3250 in 2023, allowing pneumococcal positivity rates to be calculated. Proportions are reported with Wilson 95% confidence intervals; associations were tested with Pearson chi-square and Fisher exact tests in SPSS v.23. Results: Children with detected Streptococcus pneumoniae rose from 100 to 415, corresponding to a rise in pneumococcal positivity from 3.9% (100/2546) to 12.8% (415/3250). Among the positive children, pneumococcus–Haemophilus influenzae co-detection increased from 33.0% to 45.1% (odds ratio 1.63, 95% CI 1.02–2.61; p = 0.029), while pneumococcus alone fell from 60.0% to 50.1%. Boys, urban residence, and early childhood predominated, and community-acquired pneumonia diagnoses rose from 61 to 214. No profile–demographic association reached significance (panel–residence 2023, p = 0.063). Conclusions: A post-pandemic rise in pediatric pneumococcal detections and increasing H. influenzae co-detection were observed, supporting syndromic multiplex PCR in rapid pediatric diagnostics and antimicrobial stewardship. Full article
(This article belongs to the Section Microbiology in Human Health and Disease)
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