Search Results (351)

Background/Objectives: This study aimed to evaluate sociodemographic factors, features of the acute infection, and post-infection health status in survivors of COVID-19, assessing their association with post-acute COVID-19 syndrome (PACS). Methods: A multidisciplinary public clinic in Brazil assessed COVID-19 survivors between June 2020 and February 2022. Patients were classified as having PACS or subacute infection (SI). Data on the history of the acute infection, current symptoms, physical examination, and laboratory findings were collected and analyzed using multivariate models with PACS as the outcome. Results: Among the 113 participants, 63.71% were diagnosed with PACS at a median of 130 days (IQR: 53–196) following acute symptom onset. Admission to the intensive care unit was more frequent among individuals with PACS than those with SI (83.3% vs. 65.0% respectively; p = 0.037). Symptoms significantly more prevalent in the PACS group when compared to the SI cohort included hair loss (44.4% vs. 17.1% respectively; p = 0.004), lower limb paresthesia (34.7% vs. 9.8% respectively; p = 0.003), and slow thinking speed (28.2% vs. 0.0% respectively; p < 0.001). Logistic regression revealed that only the time interval between the onset of acute symptoms and the clinical evaluation was independently associated with a PACS diagnosis (β = 0.057; 95% CI: 1.03–1.08; p < 0.001). Conclusions: Patients with PACS had a higher frequency of intensive care unit admission compared to those with subacute infection. However, in the multivariate analysis, the severity of the acute infection did not predict the final diagnosis of PACS, which was associated only with the time elapsed since symptom onset. Full article

Background: As COVID-19 transitions to an endemic phase, long COVID symptoms remain a significant public health issue affecting both physical and mental health. A notable proportion of college students report symptoms such as fatigue, cough, and brain fog persisting for weeks or months post-infection. Objectives: This study explored the prevalence and contributing factors of long COVID symptoms among both infected and uninfected students in medicine-related departments. Methods: A cross-sectional study was conducted using online self-reported questionnaires completed by 1523 undergraduate and graduate students in medicine-related departments at a medical university. Participants who had tested positive for COVID-19 within the past three months were excluded. The survey assessed long COVID symptoms, with comparisons conducted between infected and uninfected groups. Multivariate logistic regression identified risk factors associated with long COVID symptoms. Results: Of the 1118 participants, 47.5% of those with a prior COVID-19 diagnosis reported long COVID symptoms within the past month. Significant differences between the infected and uninfected groups were observed in physical, cognitive, and psychological health. Logistic regression identified that prior COVID-19 diagnosis had an association with the presence of long COVID symptoms (odds ratio = 1.48, p = 0.024) after adjusted model analysis. Meanwhile, higher anxiety levels (odds ratio = 1.09, p < 0.001) and a BMI ≥ 24 (odds ratio = 4.50, p < 0.01) were identified as significant risk factors for post-infection syndrome among previously infected students. Sex and exercise habits also influenced symptom prevalence. Conclusions: Since late 2023, with those experiencing cumulative infections surpassing half of Taiwan’s population, long COVID symptoms have persisted as a widespread concern affecting both physical and mental health, continuing into 2025. This study underscores critical risk factors and symptom patterns among students in medicine-related departments, reinforcing the urgency of sustained surveillance and targeted interventions to facilitate comprehensive recovery. Full article

Background/Objectives: In late 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a pandemic called the ‘coronavirus disease 2019’ (COVID-19). After the acute SARS-CoV-2 infection, many individuals (up to 33%) complained of unexplained symptoms involving multiple organ systems and were diagnosed as having Long COVID-19 (LC-19). Currently, LC-19 is inadequately defined, requiring the formation of consistent diagnostic parameters to provide a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy. LC-19 represents a significant burden on multiple levels. The reduced ability of workers to return to work or compromised work efficiency has led to consequences at national, economic, and societal levels by increasing dependence on community services. On a personal scale, the isolation and helplessness caused by the disease and its subsequent impact on the patient’s mental health and quality of life are incalculable. Methods: In this paper, we used Walker and Avants’ eight-step approach to perform a concept analysis of the term “Long COVID-19” and define its impact across these parameters. Results: Using this methodology, we provide an improved definition of LC-19 by connecting the clinical symptomology with previously under-addressed factors, such as mental, psychological, economic, and social effects. This definition of LC-19 features can help improve diagnostic procedures and help plan relevant healthcare services. Conclusions: LC-19 represents a complex and pressing public health challenge with diverse symptomology, an unpredictable timeline, and complex pathophysiology. This concept analysis serves as a tool for improving LC-19 definition, but it remains a dynamic disease with evolving diagnostic and therapeutic approaches, requiring deeper investigation and understanding of its long-term effects. Full article

Background and Aims: The majority of individuals with COVID-19 developed acute symptoms. Post-COVID-19 syndrome refers to the signs and symptoms of COVID-19 that persist for more than 12 weeks. The present study was conducted to estimate the prevalence and risk factors for post-COVID-19 syndrome in the Omani population. Methods: This is a cross-sectional study that was conducted at the University Hospital Center (UHC). All patients diagnosed with COVID-19 (through polymerase chain reaction PCR testing) between March 2020 and March 2022 were included. Eligible participants were interviewed through a phone call, informed about the study procedure, and invited to participate in the study. Results: The study enrolled 265 COVID-19 patients, of whom 156 (59.2%) were females and 204 (77.3%) had been vaccinated. The overall prevalence of post-COVID-19 syndrome was 48.5%. The most common symptom was fatigue (71, 26.9%), followed by joint pain (44, 16.7%). The other symptoms included loss of taste/smell (34, 12.9%), cough (32, 12.1%), palpitation (25, 9.5%), and hair loss (27, 10.2%). Unvaccinated patients showed a higher incidence of fatigue (p = 0.03) and loss of smell/taste (p = 0.01) on univariate analysis. Females were at high risk for the development of various symptoms, including fatigue, muscular pain, breathing difficulty, cough, chest pain, palpitation, headache, and hair loss. Multivariate analysis showed that female gender is a significant independent predictor (odds ratio: 3.1; p = 0.00) for the development of post-COVID-19 syndrome. Conclusions: The prevalence of post-COVID-19 syndrome among the Omani population was high, highlighting the need for targeted interventions to manage long-term symptoms in vulnerable groups. Full article

Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC). Full article

Long-COVID (LC) is characterized by diverse and persistent symptoms, potentially mirroring different molecular pathways. Recent data might offer that one of them is mediated by functional autoantibodies (fAAb) targeting G protein-coupled receptors (GPCR). Thus, the aim of this study was to investigate the clinical phenotype of patients with LC in relation to their GPCR-fAAb seropositivity. The present study recruited 194 patients with LC and profiled them based on self-reported symptoms. GPCR-fAAb seropositivity was identified by using a cardiomyocyte bioassay, testing the presence and functionality of the AAbs. Logistic regression, clustering, and decision tree analyses were applied to examine associations between GPCR-fAAb profiles and self-reported symptoms considering age and gender. The most prevalent GPCR-fAAbs in patients with LC were fAAB targeting the β2 adrenergic receptor (β2-fAAb, 92.8%), the muscarinergic M2 receptor (M2-fAAb, 87.1%), the Angiotensin II type 1 receptor (AT1-fAAb, 85.6%), and angiotensin (1–7) Mas receptor (MAS-fAAb, 85.6%). β2-fAAb showed a significant relation with dizziness, lack of concentration, and POTS, while Endothelin Type A receptor functional autoantibody (ET-A-fAAb) was significantly related to deterioration of pre-existing neurological disorders. Statistical analysis indicated a strong positive correlation between M2- and β2-fAAb; as in addition, an association of β2-fAAb and gender was observed to one of the major clinical symptoms (fatigue/PEM), a critical impact of GPCR-fAAb on LC-pathogenesis can be assumed. Summing up, the present data show that specific GPCR-fAAb are associated with distinct clinical phenotypes. Especially, the combination of M2- and β2-fAAb seemed to be essential for the LC-phenotype with a combination of fatigue/PEM and lack of concentration as major clinical symptoms. Full article

Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide’s potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection (“long-COVID”), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action. Full article

Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, p = 1.76 × 10⁻¹⁰, OR = 1.63, 95% CI: 1.40–1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, LINC01276 and FOXP4-AS1, and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with FOXP4-AS1 and FOXP4, implying that this regulatory SNP could alter the normal cellular function of FOXP4-AS1 and FOXP4. Furthermore, rs9367106 is in eQTL with the FOXP4 gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent IFIH1/MDA5 activation, leading to suppression of host innate immune responses. LINC01276 targets the MED20 gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery. Full article

Post-viral conditions, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC), share > 95% of their symptoms, but the connection between disturbances in their underlying molecular biology is unclear. This study investigates DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from patients with ME/CFS, LC, and healthy controls (HC). Reduced Representation Bisulphite Sequencing (RRBS) was applied to the DNA of age- and sex-matched cohorts: ME/CFS (n = 5), LC (n = 5), and HC (n = 5). The global DNA methylomes of the three cohorts were similar and spread equally across all chromosomes, except the sex chromosomes, but there were distinct minor changes in the exons of the disease cohorts towards more hypermethylation. A principal component analysis (PCA) analysing significant methylation changes (p < 0.05) separated the ME/CFS, LC, and HC cohorts into three distinct clusters. Analysis with a limit of >10% methylation difference and at p < 0.05 identified 214 Differentially Methylated Fragments (DMF) in ME/CFS, and 429 in LC compared to HC. Of these, 118 DMFs were common to both cohorts. Those in promoters and exons were mainly hypermethylated, with a minority hypomethylated. There were rarer examples with either no change in methylation in ME/CFS but a change in LC, or a methylation change in ME/CFS but in the opposite direction in LC. The differential methylation in a number of fragments was significantly greater in the LC cohort than in the ME/CFS cohort. Our data reveal a generally shared epigenetic makeup between ME/CFS and LC but with specific, distinct changes. Differences between the two cohorts likely reflect the stage of the disease from onset (LC 1 year vs. ME/CFS 12 years), but specific changes imposed by the SARS-CoV-2 virus in the case of the LC patients cannot be discounted. These findings provide a foundation for further studies with larger cohorts at the same disease stage and for functional analyses to establish clinical relevance. Full article

Introduction: Long COVID, or post-COVID-19 syndrome, refers to a set of persistent symptoms following SARS-CoV-2 infection without another identifiable cause. Studies indicate that symptoms can last for up to two years and affect multiple body systems. Objective: The objective of this study is to compare symptom prevalence between infected individuals pre and post-COVID-19 and non-infected individuals in a population from Southeastern Brazil. Materials and Methods: A case–control study was conducted with participants from the MonitoraCovid program in a university in Brazil. The study included adults who responded to a questionnaire about long COVID symptoms. Data were collected virtually between October 2023 and May 2024. Results: Of the 2886 individuals eligible for analysis, 75.5% reported having been positive for COVID-19. Most participants were vaccinated, with 82.99% receiving two doses. In the pre and post comparison, individuals who had COVID-19 were more likely to report increased symptoms after infection, with 95.5% of assessed conditions worsening, particularly cognitive and respiratory issues. A comparison between those who had and had not been infected with COVID-19 showed that only 6.67% of symptoms were more prevalent in the infected group. The most significant post-COVID-19 symptoms included memory problems, fatigue, and shortness of breath, though some conditions, such as anxiety and sleep disturbances, were less common among those who had COVID-19. Conclusions: The findings reinforce that long COVID significantly impacts cognitive health, highlighting the importance of monitoring previously infected individuals. The study also emphasizes the need for further research in Global South contexts to better understand the long-term implications of COVID-19. Full article

The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood–brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus–immune–brain axis in long COVID and inform effective clinical management. Full article

Background: Post-COVID syndrome is characterized by persistent symptoms such as dyspnea, fatigue, and reduced exercise tolerance, which can significantly impair pulmonary function and quality of life. Pulmonary rehabilitation has been proposed as a potential intervention to address these challenges. This study aimed to evaluate the effects of a pulmonary rehabilitation program on pulmonary function, inflammatory markers, and quality of life in patients with post-COVID syndrome. Methods: A prospective, interventional, non-randomized clinical trial was conducted involving 77 participants (mean age 59.4 ± 11.6 years; 39% female) who attended a post-COVID care clinic in Rzeszów, Poland. The intervention included supervised respiratory and aerobic exercises, muscle strengthening, and body balance therapy, alongside motivational breathing therapy. Pulmonary function (spirometry, plethysmography, gasometry), inflammatory markers (CRP, WBC, D-dimer), and quality of life (WHOQOL-BREF) were assessed pre- and post-intervention. Results: Significant improvements were observed in pulmonary function parameters post-rehabilitation, including increases in forced vital capacity (FVC, 75% to 78.4%, p < 0.001), forced expiratory volume in one second (FEV1, 78.2% to 80.5%, p < 0.001), and total lung capacity (TLC, 67.3% to 71%, p < 0.001). The diffusing capacity for carbon monoxide (DLCO) improved by 6.2% (p < 0.001). Arterial oxygen pressure (PaO₂) increased by 7.6 mmHg (p < 0.001). Markers of inflammation, including CRP (8.9 to 1.3 mg/dL, p < 0.001) and d-dimer (1722.2 to 203.4 ng/mL, p < 0.001), showed significant reductions. Quality of life improved across physical, psychological, and environmental domains. Sex, BMI, and baseline inflammatory markers were significant determinants of rehabilitation outcomes. Conclusions: A pulmonary rehabilitation program significantly improved pulmonary function, reduced systemic inflammation, and enhanced quality of life in individuals with post-COVID syndrome. The findings highlight the importance of tailored rehabilitation in mitigating long-term post-COVID sequelae. Future research should explore the long-term effects of rehabilitation and its applicability in diverse populations. Full article

While there are many postulates for the etiology of post-viral chronic fatigue and other symptomatology, little is known. We draw on our past experience of these syndromes to devise means which can expose the primary players of this malady in terms of a panoply participating biomolecules and the state of the stool microbiome. Using databases established from a large dataset of patients at risk of colorectal cancer who were followed longitudinally over 3 decades, and a smaller database dedicated to building a Long PASC cohort (Post-Acute Sequelae of COVID-19), we were able to ascertain factors that predisposed patients to (and resulted in) significant changes in various biomarkers, i.e., the stool microbiome and serum cytokine levels, which we verified by collecting stool and serum samples. There were significant changes in the stool microbiome with an inversion from the usual Bacillota and Bacteroidota species. Serum cytokines showed significant differences in MIP-1β versus TARC (CC chemokine ligand 17) in patients with either PASC or COVID-19 (p < 0.02); IL10 versus IL-12p70a (p < 0.02); IL-1b versus IL-6 (p < 0.01); MCP1 versus TARC (p < 0.03); IL-8 versus TARC (p < 0.002); and Eotaxin3 versus TARC (p < 0.004) in PASC. Some changes were seen solely in COVID-19, including MDC versus MIP-1α (p < 0.01); TNF-α versus IL-1-β (p < 0.06); MCP4 versus TARC (p < 0.0001). We also show correlates with chronic fatigue where an etiology was not identified. These findings in patients with positive criteria for PASC show profound changes in the microbiome and serum cytokine expression. Patients with chronic fatigue without clear viral etiologies also have common associations, including a history of tonsillectomy, which evokes a likely immune etiology. Full article

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID are complex multisystem conditions that pose significant challenges in healthcare. Accumulated research evidence suggests that ME/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating potential shared metabolic dysfunctions. This study aims to systematically explore shared metabolic disturbances in the muscle tissue of patients. Utilizing genome-wide metabolic modeling, we identified key metabolic irregularities in the muscle of patients with ME/CFS, notably the downregulation of the alanine and aspartate metabolism pathway and the arginine and proline metabolism pathway. Further, in silico knockout analyses suggested that supplementation with aspartate (ASP) or asparagine (ASN) could potentially ameliorate these metabolic deficiencies. In addition, assessments of metabolomic levels in Long COVID patients also showed the significant downregulation of ASP during post-exertional malaise (PEM) in both muscle and blood. Consequently, we propose that a combination of l-ornithine and l-aspartate (LOLA) is a potential candidate to alleviate metabolic symptoms in ME/CFS and Long COVID for future clinical trials. Full article

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis of overwhelming morbidity and mortality and emerged various mutant strains. Patients recovering from SARS-CoV-2 develop post-acute COVID syndrome, commonly known as long COVID (LC), lasting up to 12 weeks or even longer. The mechanism has yet to be clarified. COVID-19 pseudovirus is a suitable model to understand the infection of the COVID-19 virus to cells, which is suitable to see the acute change in cells owing to its one-time infection and inactivation. The ACE2-293T cell infected by COVID-19 pseudovirus was used in this study. After the infection and removal of the pseudovirus, high amounts of ferrous ions were accumulated in mitochondria and then released into the cytosol. Reactive oxygen species (ROS) accumulation was formed and caused mitochondrial dysfunction. To evaluate the effect of nutritional strategy on ferrous ion accumulation and mitochondrial dysfunction, lactoferrin, Q10 and Echinacea purpurea extract (EPE) were used in this study. Results showed that lactoferrin, Q10 and EPE could improve mitochondrial dysfunction by reducing the accumulation of ferrous ions and ROS in the mitochondria. HPLC analysis showed that EPE contained rich caffeic acid, and it also showed perfect improvement in mitochondrial dysfunction. In conclusion, cells infected with pseudovirus could increase the accumulation of ferrous ions and ROS in mitochondria and be released into the cytosol after removing pseudovirus, thereby causing mitochondrial dysfunction. Lactoferrin, Q10 and EPE were an effective nutritional strategy to suppress ferrous ion accumulation, ROS formation and advanced mitochondrial dysfunction. Full article