Search Results (187)

Background/Objectives: Multisystem inflammatory syndrome in children (MIS-C), a rare but serious post-acute hyperinflammatory condition that occurs in children 2–6 weeks after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or exposure, varies between countries. Despite its serious nature, most children recover without any sequelae. The most frequently reported long-term sequelae are coronary artery aneurysms. This study aimed to describe the epidemiological profile, clinical characteristics (including cardiac manifestations), treatment, and outcomes of multisystem inflammatory syndrome in children (MIS-C) under 14 years of age with SARS-CoV-2 between February 2020 and November 2021 in Kuwait. Methods: Data on sociodemographic factors, co-morbidities, presenting signs and symptoms, as well as laboratory and echocardiography findings were retrieved from the Pediatric COVID registry (PCR-Q8 registry). Results: Of the one hundred and two patients with a provisional diagnosis of MIS-C, eighty-three patients fulfilled the WHO criteria of MIS-C. Thirty-nine of the MIS-C patients were admitted to the intensive care unit, and only one child died due to cardiogenic shock. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Most (63% (10/16)) of the patients had coronary abnormalities, nine patients (56%) had myocardial dysfunction, and six patients (38%) had dual pathologies. Pericarditis occurred in three patients only, whilst six patients (38%) had dual pathologies. Pericarditis occurred in three patients only. Conclusions: MIS-C appears to affect younger children in Kuwait than in other countries; however, the clinical pattern is consistent with other countries. Further studies of an analytical nature are recommended to identify the risk factors associated with MIS-C and its cardiac sequalae to allow for proactive risk reduction. Full article

Background: Currently available immunological tests for SARS-CoV-2 assess only antibody responses. Despite the growing evidence that T cells play a crucial role in protection, especially against emerging viral variants, no routine test is available to determine T cell immunity. The prognostic value of SARS-CoV-2-specific antibodies for determining whether individuals are immune and protected against disease remains uncertain. This is in part due to the following: (a) specificity and limitations such as the sensitivity of antibody tests, and (b) the lack of correlation between antibody titers (quantity) and the antiviral function of antibodies (quality). Approximately a quarter of SARS-CoV-2-infected patients with symptoms fail to show seroconversion in serological assays. Methods: The current report describes the development and application of a whole-blood-based assay to detect previous exposure to SARS-CoV-2. Whole blood is stimulated with SARS-CoV-2-derived peptides identified during assay development and stimulation-induced cytokines quantified using a multiplex testing platform. The resulting cytokine profiles are generated using computational tools to identify previous exposure to the virus. Results: The application of the assay revealed a lack of self-awareness of individuals’ COVID-19 infection history and demonstrated the value of this new assay to assess the prevalence of SARS-CoV-2 exposure history and immunity in populations. Conclusions: Positive responses in this assay can facilitate the identification of underlying causes of unexplained symptoms and provide clinically actionable insights for healthcare applications, including in the continued conundrum of post-acute sequela of SARS-CoV-2 infection (PASC or “long COVID”), for which both diagnosis and management remain challenging. Full article

Thrombophilic conditions, conditions where blood has a tendency to form thrombi due to abnormal coagulatory processes, can affect the trajectory of diseases such as Post-Acute Sequelae of SARS-CoV-2 Infection, better known as Long COVID (LC), by worsening symptoms and complicating outlooks. As a comorbidity in pro-coagulatory diseases such as COVID-19 and LC, patients with thrombophilic conditions may experience worse symptoms than their peers, due to this elevated level of hypercoagulation. A 15-week literature review through the public PubMed database was conducted to investigate the severity, mechanisms, and symptom profiles of thrombophilic patients with LC. Papers were only included if samples included participants with pre-existing tendencies for hypercoagulable states, and confirmation of SARS-CoV-2 infection via a Polymerase Chain Reaction test. Each paper included in this review was analyzed by topic and assessed for eligibility against the Joanna Briggs Institute’s Critical Appraisal tool. Each paper was also assessed for biases. Results from the 6 papers included in this review showed that LC could be predicted following COVID-19 illness by a hypercoagulable blood profile, indicating that LC may be linked to chronic hypercoagulation and inflammation post-infection. Additionally, symptoms linked to microthrombi formation, such as hair loss, arrhythmia, and dizziness, were exhibited more frequently in patients with thrombophilia and/or thrombophilic conditions, indicating that those with thrombophilic conditions may exhibit unique LC symptom profiles compared to healthy controls. This paper’s research is preliminary and thus is limited in the strength of its findings; However, further research into LC and its interactions with co-morbidities like thrombophilic conditions would aid in the development of better treatment plans for patients, such as the usage of anticoagulants or screening for hypercoagulable blood profiles post-COVID-19 to assess patient risk. Full article

Post-acute sequelae of SARS-CoV-2 infection (long COVID) present with persistent fatigue, cognitive impairment, and autonomic and multisystem dysfunctions that often go unnoticed by standard diagnostic tests. Increasing evidence suggests that mitochondrial dysfunction and oxidative stress are central drivers of these post-viral sequelae. Viral infections, particularly SARS-CoV-2, disrupt mitochondrial bioenergetics by altering membrane integrity, increasing mitochondrial reactive oxygen species (mtROS), and impairing mitophagy, leading to sustained immune activation and metabolic imbalance. This review synthesizes an understanding of how mitochondrial redox signaling and impaired clearance of damaged mitochondria contribute to chronic inflammation and multisystem organ symptoms in both long COVID and post-vaccine injury. We discuss translational biomarkers and non-invasive techniques, exploring therapeutic strategies that include pharmacological, non-pharmacological, and nutritional approaches, as well as imaging modalities aimed at assessing and restoring mitochondrial health. Recognizing long COVID as a mitochondrial disorder that stems from redox imbalance will open new options for personalized treatment and management guided by biomarkers. Future clinical trials are essential to validate these approaches and translate mitochondrial resuscitation into effective care for patients suffering from long COVID and related post-viral syndromes. Full article

Background: SARS-CoV-2, originally described as a respiratory pathogen, has been identified as a multisystem disease with complex and interconnected pathophysiological processes. Methods: The PRISMA framework was used to systematically review the evidence and identify and synthesize it in PubMed, Scopus, and Web of Science databases between January 2020 and May 2025. Of the 1410 screened records, 161 peer-reviewed studies involving more than 2 million patients were included in the analysis. The frequency of organ involvement, important biomarkers, and long-term outcomes were derived, and the quality of the studies was assessed using standardized tools. Results: The quantitative synthesis showed that 78%, 32%, 43%, and 28% of hospitalized patients had pulmonary, cardiovascular, 43% neurological, and 28% renal issues, respectively, with 10–35% showing persistent organ dysfunction at 6 months post-infection. The most common were cytokine storm (IL-6 (Interleukin-6) > 100 pg/mL in 72% of severe cases), endothelial dysfunction (biomarkers elevated in 87% of patients), and microvascular thrombosis (D-dimer > 2000 ng/mL in 46% of patients). Most domains were scored as having moderate-to-high confidence in the quality assessment. Conclusions: COVID-19 has long-term, multi-organ sequelae that require integrated multidisciplinary management. Healthcare systems should be ready to participate in long-term monitoring, rehabilitation, and special therapeutic development. The results offer a strong evidence base for clinical practice and post-pandemic health policy. Full article

Background: Persistent fatigue is among the most commonly reported symptoms in patients suffering from post-acute sequelae of SARS-CoV-2 infection (long COVID). Autonomic dysfunction, measurable via heart rate variability, has been implicated as a contributing factor. Osteopathic manipulative treatment is a manual therapeutic approach that targets autonomic balance and may offer a novel intervention for long COVID-related fatigue. Methods: In this single-blind, randomized controlled trial, 42 participants (mean age 51 ± 11 years; fatigue severity score: 31 ± 5 points) with long COVID and persistent fatigue ≥12 weeks post-infection were allocated to either a 45 min standardized osteopathic treatment (n = 21) or a sham-treatment group (n = 21). Heart rate variability was assessed using a 10 min resting electrocardiogram before intervention, immediately after, and again 48 h later. The analysis of heart rate variability encompassed time-domain indices, including the root mean square of successive differences, the standard deviation of normal-to-normal intervals, mean heart rate, and mean RR interval. Additionally, frequency-domain measures such as low-frequency, high-frequency, total power, and the LF/HF ratio were considered. Results: The osteopathy group showed a statistically significant increase in root mean square of successive differences post-treatment (p < 0.01), accompanied by a decrease in the stress index (p < 0.05) and an increase in the mean of the standard deviations of RR intervals (p < 0.05). Significant between-group differences were observed for mean heart rate and mean of RR intervals (p < 0.05). Frequency-domain measures also improved significantly from baseline in the intervention group. Outlier patterns suggest potential subgroup effects, possibly due to underlying dysautonomia. Conclusions: A single session of osteopathic treatment significantly enhanced short-term heart rate variability in long COVID patients with fatigue. These findings highlight the potential role of manual autonomic modulation as a supportive therapy in long COVID management. Further research is needed to assess the long-term effects and optimal treatment frequency of osteopathic manipulative treatment in this population. Full article

Coronavirus disease 2019 (COVID-19) in adults is well characterized and associated with multisystem dysfunction. A subset of patients develop post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID), marked by persistent and fluctuating organ system abnormalities. In children, distinct clinical and pathophysiological features of COVID-19 and long COVID are increasingly recognized, though knowledge remains limited relative to adults. The exponential expansion of the COVID-19 literature has made comprehensive appraisal by individual researchers increasingly unfeasible, highlighting the need for new approaches to evidence synthesis. Large language models (LLMs) such as the Generative Pre-trained Transformer (GPT) can process vast amounts of text, offering potential utility in this domain. Earlier versions of GPT, however, have been prone to generating fabricated references or misrepresentations of primary data. To evaluate the potential of more advanced models, we systematically applied GPT-4 to summarize studies on pediatric long COVID published between January 2022 and January 2025. Articles were identified in PubMed, and full-text PDFs were retrieved from publishers. GPT-4-generated summaries were cross-checked against the results sections of the original reports to ensure accuracy before incorporation into a structured review framework. This methodology demonstrates how LLMs may augment traditional literature review by improving efficiency and coverage in rapidly evolving fields, provided that outputs are subjected to rigorous human verification. Full article

SARS-CoV-2 infection can be followed by prolonged symptoms, signs and sequelae, collectively known under the term Long COVID. Hundreds of millions are estimated to suffer from Long COVID. Long COVID, therefore, is a public health crisis that deserves the utmost urgency from all relevant stakeholders, from policymakers to advocacy groups, researchers and healthcare providers. The development of effective definitions and guidelines for Long COVID is crucial to support patients and carers. In this review, I address the following two case definitions of Long COVID developed in the US as a case study for a broader discussion on the sequelae of SARS-CoV-2 infection: the U.S. Government (USG) working definition for Long COVID and the NASEM definition published in 2024. In the first part of this review, I provide a critical appraisal of the USG in light of research, pathophysiology and lived experience, building upon my intervention as a patient expert on a National Academies of Sciences, Engineering, and Medicine (NASEM) panel for defining Long COVID, which examined the USG. In the second part, I raise some pressing concerns to address when approaching Long COVID as a disease entity and as a concept, which I originally submitted to NASEM. In the third part, I offer a critical appraisal of the NASEM definition, the most recent benchmark for Long COVID in the US. The review highlights the importance of broad, expansive and inclusive definitions for Long COVID, accounting for the disease’s heterogeneous, fluctuating and multi-system manifestations. Clinical case definitions for Long COVID must retain their focus on the broader spectrum and scope of the disease entity, while incorporating feedback from people with lived experience, advocates and patient-researchers. Full article

A significant number of individuals recovering from COVID-19 continue to experience persistent symptoms, collectively referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or long COVID. Among these complications, post-COVID-19 pulmonary fibrosis (PC19-PF) is one of the most severe long-term outcomes, characterized by progressive lung scarring, chronic respiratory impairment, and reduced quality of life. Despite the increasing prevalence of PC19-PF, its underlying mechanisms remain poorly understood. In this review, we provide a comprehensive overview of PC19-PF, including its epidemiology, clinical manifestations, diagnostic strategies, and mechanistic insights. Additionally, we highlight the shared pathways between PC19-PF and other fibrotic lung diseases and discuss emerging therapeutic strategies. This review consolidates emerging insights from both clinical and experimental studies to advance our understanding of PC19-PF pathogenesis and guide the development of mechanism-based therapeutic approaches. Full article

Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu—characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)—and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals. Full article

The COVID-19 pandemic, caused by SARS-CoV-2, has led to a wide range of acute and chronic disease manifestations. While most infections are mild, a significant number of patients develop severe illness marked by respiratory failure, thromboinflammation, and multi-organ dysfunction. In addition, post-acute sequelae—commonly known as long-COVID—can persist for months. Recent studies have identified the emergence of diverse autoantibodies in COVID-19, including those targeting nuclear antigens, phospholipids, type I interferons, cytokines, endothelial components, and G-protein-coupled receptors. These autoantibodies are more frequently detected in patients with moderate to severe disease and have been implicated in immune dysregulation, vascular injury, and persistent symptoms. This review examines the underlying immunological mechanisms driving autoantibody production during SARS-CoV-2 infection—including molecular mimicry, epitope spreading, and bystander activation—and discusses their functional roles in acute and post-acute disease. We further explore the relevance of autoantibodies in maternal–fetal immunity and comorbid conditions such as autoimmunity and cancer, and we summarize current and emerging therapeutic strategies. A comprehensive understanding of SARS-CoV-2-induced autoantibodies may improve risk stratification, inform clinical management, and guide the development of targeted immunomodulatory therapies. 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

Background/Objectives: To investigate the incidence of new-onset diabetic retinopathy (DR) in individuals with pre-existing type 2 diabetes (T2D) up to 3 years post SARS-CoV-2 infection. Methods: This retrospective study consisted of 5151 COVID-19 and 5151 propensity-matched non-COVID-19 patients with T2D in the Montefiore Health System between 1 March 2020 and 17 January 2023. The primary outcome was new-onset DR at least 2 months after the index date up to 17 January 2023. Matching for index date between groups was also used to ensure the same follow-up duration. Hazard ratios (HRs) were computed, adjusted for competing risks. Results: T2D patients with COVID-19 had a higher cumulative incidence of DR than T2D patients. The unadjusted HR for COVID-19 status for developing new DR was 2.44 [1.60, 3.73], p < 0.001. The adjusted HR was 1.70 [1.08, 2.70], p < 0.05, and the adjusted HR for prior insulin use was 3.28 [2.10, 5.12], p < 0.001. Sex, ethnicity, and major comorbidities had no significant association with outcome. Conclusions: T2D patients who contracted COVID-19 exhibited a significantly higher risk of developing DR within three years post infection compared to propensity-matched controls. The increased incidence was primarily driven by greater pre-existing insulin usage and SARS-CoV-2 infection in the COVID-19 positive cohort. Full article

Narrative review synthesizes the most current literature on the SARS-CoV-2 XEC variant, focusing on its genomic evolution, immune evasion characteristics, epidemiological dynamics, and public health implications. To achieve this, we conducted a structured search of the literature of peer-reviewed articles, preprints, and official surveillance data from 2023 to early 2025, prioritizing virological, clinical, and immunological reports related to XEC and its parent lineages. Defined by the distinctive spike protein mutations, T22N and Q493E, XEC exhibits modest reductions in neutralization in vitro, although current evidence suggests that mRNA booster vaccines, including those targeting JN.1 and KP.2, retain cross-protective efficacy against symptomatic and severe disease. The XEC strain of SARS-CoV-2 has drawn particular attention due to its increasing prevalence in multiple regions and its potential to displace other Omicron subvariants, although direct evidence of enhanced replicative fitness is currently lacking. Preliminary analyses also indicated that glycosylation changes at the N-terminal domain enhance infectivity and immunological evasion, which is expected to underpin the increasing prevalence of XEC. The XEC variant, while still emerging, is marked by a unique recombination pattern and a set of spike protein mutations (T22N and Q493E) that collectively demonstrate increased immune evasion potential and epidemiological expansion across Europe and North America. Current evidence does not conclusively associate XEC with greater disease severity, although additional research is required to determine its clinical relevance. Key knowledge gaps include the precise role of recombination events in XEC evolution and the duration of cross-protective T-cell responses. New research priorities include genomic surveillance in undersampled regions, updated vaccine formulations against novel spike epitopes, and long-term longitudinal studies to monitor post-acute sequelae. These efforts can be augmented by computational modeling and the One Health approach, which combines human and veterinary sciences. Recent computational findings (GISAID, 2024) point to the potential of XEC for further mutations in under-surveilled reservoirs, enhancing containment challenges and risks. Addressing the potential risks associated with the XEC variant is expected to benefit from interdisciplinary coordination, particularly in regions where genomic surveillance indicates a measurable increase in prevalence. 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