@article {pmid40470564,
year = {2025},
author = {Iannuccelli, C and Favretti, M and Dolcini, G and Di Carlo, M and Pellegrino, G and Bazzichi, L and Atzeni, F and Lucini, D and Varassi, G and Leoni, MLG and Fornasari, DMM and Conti, F and Salaffi, F and Sarzi Puttini, P and Di Franco, M},
title = {Fibromyalgia: one year in review 2025.},
journal = {Clinical and experimental rheumatology},
volume = {},
number = {},
pages = {},
doi = {10.55563/clinexprheumatol/buhd2z},
pmid = {40470564},
issn = {0392-856X},
abstract = {Fibromyalgia (FM) is a chronic syndrome characterised by widespread pain, high prevalence, and a significant impact on quality of life. Despite extensive research, its pathogenesis and treatment remain only partially understood, driving continued investigation throughout 2024. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system has been linked to chronic stress responses and neuroinflammation, with neuroimaging and preclinical studies confirming altered pain and stress processing. Low-grade inflammation and metabolic disturbances, including cytokine imbalance and increased adipose tissue infiltration, further exacerbate symptoms. Alterations in the gut microbiota contribute to immune and emotional dysregulation. MRI studies continue to reveal brain changes that differentiate FM from other chronic pain disorders. Multi-omics approaches, including transcriptomic and metabolomic analyses, show promise as diagnostic biomarkers. Mitochondrial dysfunction also emerges as a key factor, since impaired energy metabolism seems to correlate with symptom severity. From a clinical perspective, recent studies have explored under-recognised aspects of FM, such as sexual and cognitive dysfunction, the role of gender, environmental exposures, and the disease's impact on relationships and family life. The differential diagnosis of FM and long COVID has ignited discussion about potential shared mechanisms. Conversely, residual pain in inflammatory diseases remains insufficiently addressed. Therapeutically, non-pharmacological strategies, particularly physical activity and psychosocial interventions, remain fundamental. Emerging areas such as non-invasive neuromodulation, psychedelic therapies, and the integration of technologies like virtual reality and artificial intelligence are opening new frontiers in treatment, patient care, and research. These advances underscore the multifactorial nature of FM and the need for personalised, interdisciplinary approaches.},
}

@article {pmid40465774,
year = {2025},
author = {Salmam, I and Dubé, MO and Zahouani, I and Ramos, A and Desmeules, F and Best, KL and Roy, JS},
title = {The impact of long COVID on physical and cardiorespiratory parameters: A systematic review.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0318707},
doi = {10.1371/journal.pone.0318707},
pmid = {40465774},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/physiopathology/complications ; SARS-CoV-2 ; Respiratory Function Tests ; Adult ; Exercise Tolerance ; },
abstract = {BACKGROUND: Since the emergence of COVID-19, millions worldwide have continued to experience persistent symptoms months after infection. Among these, physical and cardiorespiratory impairments are frequently reported, but remain poorly understood. This systematic review aimed to identify and synthesize evidence regarding physical and cardiorespiratory impairments in individuals with long COVID, defined as symptoms persisting for at least three months post-infection.

METHODS AND FINDINGS: A structured search was conducted across the MEDLINE, Embase, CINAHL, and Web of Science databases to identify cross-sectional and longitudinal cohort studies on physical and cardiorespiratory deficits in adults with long COVID. Twenty-two studies involving 3,041 adults with long COVID were included. Critical appraisal using the JBI-APT indicated that most studies had clear inclusion criteria (17/22), well-defined study populations (17/22), and valid exposure measurements (16/22), though confounding factors were often unaddressed (9/22 unclear or not reported). Findings indicate that while adults with long COVID displayed normal pulmonary function at rest, including Forced Vital Capacity (FVC), Forced Expiratory Volume (FEV1), Total Lung Capacity (TLC), and resting Arterial oxygen saturation (SpO2), significant impairments in exercise capacity were identified. Notably, all studies assessing the 6-minute walk test (6MWT) reported reduced distances, consistently falling below the 50th percentile of normative values. Additionally, VO₂peak was decreased in most studies (7/10), falling below 80% of the predicted value, indicating impaired aerobic capacity. Lower Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) values were observed in three out of six studies, with values below 75% of predicted, suggesting impaired gas exchange efficiency during exertion.

CONCLUSION: Despite preserved resting lung function, these findings highlight significant physical deconditioning in Long COVID adults, with substantial reduction in exercise capacity. Routine assessments should include more sensitive measures, such as the 6MWT and VO₂peak, to detect subtle exercise limitations, even in patients with normal resting SpO₂, to better inform rehabilitation interventions.},
}

Humans
*COVID-19/physiopathology/complications
SARS-CoV-2
Respiratory Function Tests
Adult
Exercise Tolerance

@article {pmid40464778,
year = {2025},
author = {Barbosa, NL and Rangel Agra Oliveira, T and Nóbrega, LD and Araújo, TTF and Bezerra, SRS and Oliveira, GM and Do Nascimento, RM and Nogueira, PAMS and Tomaz, AF and Fernandes, ATDNSF},
title = {Prevalence and characteristics of respiratory and cardiovascular sequelae in post-COVID-19 syndromes: a scoping review.},
journal = {Expert review of respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1080/17476348.2025.2515992},
pmid = {40464778},
issn = {1747-6356},
abstract = {INTRODUCTION: Post acute and Long COVID-19 are a public health issue, marked by persistent respiratory and cardiovascular symptoms such as dyspnea and palpitations. These complications often extend beyond the acute phase, affecting even individuals with mild or moderate COVID-19. This article reviews the clinical impact of long COVID-19 and emphasizes the need for a multidisciplinary approach to management.

AREAS COVERED: A comprehensive literature search was conducted through PubMed, Medline, CINAHL, SciELO, and LILACS to identify studies published up to 28 October 2024, reporting on respiratory and cardiovascular sequelae in long COVID-19. This review examines the prevalence and characteristics of persistent symptoms such as dyspnea, cough, and palpitations, as well as the associated risk factors and assessment methods.

EXPERT OPINION: Long COVID-19 represents a significant healthcare challenge, underscoring the need for standardized protocols for diagnosis and treatment. A multidisciplinary approach is crucial to address the diverse symptoms of affected patients. Future research should focus on understanding the underlying pathophysiology, and developing targeted therapeutic strategies to improve patient outcomes.},
}

@article {pmid40453253,
year = {2025},
author = {Boorle, NVLD and Kurra, NC and Gandrakota, N and Modi, K and Sudireddy, K and Irfan, SA and Jain, A and Parikh, PA and Jillella, D},
title = {Central Nervous System Manifestations of Long COVID: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83247},
pmid = {40453253},
issn = {2168-8184},
abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been one of the most widespread and devastating global pandemics, impacting hundreds of millions of people worldwide. After the cessation of active infection, the disease continues to have a disabling impact due to the persistence of fatigue, brain fog, anxiety, and depression - among the most common symptoms. This study explores the progression of neurological symptoms over 12 months and beyond following an initial diagnosis of COVID-19. Through an electronic search of eligible studies from PubMed, the Cochrane Trial Register, and Google Scholar, 10 studies were included for qualitative analysis. The systematic review highlights the similarities and differences in findings across the included studies. Olfactory dysfunction was prevalent in 0.9%-51% of individuals, and taste impairment was observed in 1.1%-21.3%. At 12 months, anxiety was more prevalent (3.5%-29%) than depression (3.5%-26%). Fatigue was the predominant neurocognitive complaint in 56% of individuals with severe COVID-19. Nearly half of individuals reported sleep difficulties. Memory impairment, followed by headaches and dizziness, also constitutes neurocognitive symptoms reported at 12 months. Our study found that there is a significant neurological burden one year following the diagnosis of COVID-19. Further studies exploring the pathological mechanisms of long-term COVID-19 are necessary to better delineate the mechanisms behind several long-term neurological manifestations of COVID-19.},
}

@article {pmid40447142,
year = {2025},
author = {Vreeman, ECA and Pillay, J and Burgess, JK},
title = {Post-COVID pulmonary sequelae: Mechanisms and potential targets to reduce persistent fibrosis.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {108891},
doi = {10.1016/j.pharmthera.2025.108891},
pmid = {40447142},
issn = {1879-016X},
abstract = {After the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) pandemic, the emergence of long-term sequelae post-infection poses a new healthcare challenge. Following initial infection with SARS-CoV-2, approximately 1 in 10 people experience post-acute sequelae of COVID-19 (PASC), also known as long COVID. PASC can affect the entire body, with the airways and lungs being a primary target of the initial viral infection. Many post-COVID symptoms have been associated with fibrotic lung lesions and diminished respiratory function. The reversibility, persistence, or progression of post-COVID-19 pulmonary fibrosis is still a topic of debate. We aimed to compare current findings and examined similar viral infections from the past, to increase understanding of prevalence, persistence and possible pharmacological targets of post-COVID-19 pulmonary fibrosis. Recent studies have documented PASC symptoms persisting up to 3 years post-recovery, and lung impairments present after 15 years after infection with the similar SARS-CoV virus in 2003. These findings suggest the potential for long-term pulmonary fibrosis following SARS-CoV-2 infection, highlighting the need for new anti-fibrotic treatments capable of reversing pulmonary fibrosis. Besides the approved anti-fibrotics, pirfenidone and nintedanib, other promising treatments include histone deacetylase inhibitors, angiotensin receptor blockers and mesenchymal stem cells. The pathophysiological mechanisms underlying post-COVID-19 pulmonary fibrosis are still incompletely understood, necessitating future research to clarify the development of persistent post-COVID-19 pulmonary fibrosis following SARS-CoV-2 infection. Given the widespread transmission of SARS-CoV-2, even a low prevalence of persistent post-COVID-19 pulmonary fibrosis would represent a significant public health concern for which therapeutic strategies are essential to identify.},
}

@article {pmid40438846,
year = {2025},
author = {Idris Fadul, AA and Osman Mohamed, AA and Mohammed Ahmed, AAS and Elmobark, S and Merghani Hammour, AS and Elgaleel Khir Elsiad, NMN and Mohammed Elhaj, EA},
title = {Post-coronavirus Disease 2019 (COVID-19) Cardiovascular Manifestations: A Systematic Review of Long-Term Risks and Outcomes.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e83083},
pmid = {40438846},
issn = {2168-8184},
abstract = {Emerging evidence suggests that coronavirus disease 2019 (COVID-19) survivors face increased risks of cardiovascular complications, but the long-term risks, underlying mechanisms, and clinical implications remain incompletely characterized. This systematic review synthesizes current evidence on post-COVID-19 cardiovascular manifestations, evaluating their incidence, pathophysiology, and outcomes. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Fifteen observational studies (cohort, case-control, cross-sectional) meeting predefined eligibility criteria, confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, cardiovascular outcomes assessed ≥4 weeks post-infection, sample sizes >10, and peer-reviewed publication, were included. The risk of bias was assessed using the Newcastle-Ottawa Scale. The multinational studies (United States, Europe, Asia, South America) involved diverse populations (n=80-8,126,462), with follow-up durations ranging from three to 24 months. Mechanisms such as endothelial dysfunction, myocardial inflammation, and autonomic dysregulation were consistently supported across studies via imaging (e.g., cardiac MRI) and biomarkers (e.g., troponin, C-reactive protein (CRP)). Persistent arrhythmias and subclinical myocardial injury were directly demonstrated in 40-60% of patients. Worse outcomes were associated with hospitalization during acute infection, preexisting cardiovascular disease, and metabolic syndrome. Heterogeneity in follow-up durations may limit the detection of very-late-onset complications, though risks remained elevated across all intervals. Individualized management strategies should include cardiovascular imaging (echocardiography, MRI), biomarker profiling, and tailored pharmacotherapy (anti-inflammatory agents, anticoagulants). The ethical rationale for randomized trials is now strengthened by the clear evidence of long-term risks; ongoing trials are testing targeted anti-inflammatory and anticoagulant regimens. These findings underscore the necessity of systematic cardiovascular surveillance and risk-stratified care for COVID-19 survivors. Future research should prioritize extended follow-up studies and randomized controlled trials (RCTs) to optimize interventions for this growing population.},
}

@article {pmid40436612,
year = {2025},
author = {Daynes, E and Barker, RE and Jones, AV and Walsh, JA and Nolan, CM and Man, WD and Singh, SJ and Greening, NJ and Houchen-Wolloff, L and Evans, RA},
title = {Determining the minimum important differences for field walking tests in adults with long-term conditions: a systematic review and meta-analysis.},
journal = {European respiratory review : an official journal of the European Respiratory Society},
volume = {34},
number = {176},
pages = {},
doi = {10.1183/16000617.0198-2024},
pmid = {40436612},
issn = {1600-0617},
mesh = {Humans ; *Walk Test ; *Exercise Tolerance ; Time Factors ; Predictive Value of Tests ; Male ; Female ; *Minimal Clinically Important Difference ; Reproducibility of Results ; Adult ; Middle Aged ; *Lung/physiopathology ; *Walking ; Aged ; *Respiratory Tract Diseases/diagnosis/physiopathology/therapy ; *Heart Diseases/diagnosis/physiopathology ; Prognosis ; *Exercise Test ; *Nervous System Diseases/diagnosis/physiopathology ; Chronic Disease ; },
abstract = {IMPORTANCE: The minimum important difference (MID) for field walking tests aims to improve interpretation of outcomes, but the volume and heterogeneity of MIDs for these tests is challenging. We aimed to determine the MID for the 6-min walk distance (6MWD), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with long-term conditions.

METHODS: This systematic review included studies that generated a MID using an anchor-based approach in patients with long-term conditions for the 6MWD, ISWT or ESWT field walking tests. Studies were screened and data extracted by independent reviewers. Meta-analyses were performed using RevMan.

RESULTS: 42 studies were included in the analyses, involving n=13 949 participants. Of these, 12 studies involving exercise as an intervention were included in the meta-analyses to produce MIDs, presented as mean (95% confidence interval). The MID for the 6MWD was 25 m (24-26 m) for respiratory conditions, 23 m (8-37 m) for cardiac conditions and 37 m (26-49 m) for neurological/musculoskeletal conditions. The MID for the ISWT was 48 m (39-57 m) for respiratory conditions and 70 m (55-85 m) for cardiac conditions. The MID for ESWT in COPD was 159 s (94-224 s). The pooled MID across conditions within exercise interventions was 26 m (22-40 m) for the 6MWD and 53 m (44-62 m) for the ISWT, with reasonable heterogeneity (I[2]=48% and I[2]=47%, respectively).

CONCLUSION: We propose new MIDs for exercise interventions using anchor-based methodology in long‑term conditions for the 6MWD, ISWT and ESWT. These can be used internationally for meta‑analyses where studies have used different field walking tests, to optimise trial sample size calculations, and for clinical service benchmarking.},
}

Humans
*Walk Test
*Exercise Tolerance
Time Factors
Predictive Value of Tests
Male
Female
*Minimal Clinically Important Difference
Reproducibility of Results
Adult
Middle Aged
*Lung/physiopathology
*Walking
Aged
*Respiratory Tract Diseases/diagnosis/physiopathology/therapy
*Heart Diseases/diagnosis/physiopathology
Prognosis
*Exercise Test
*Nervous System Diseases/diagnosis/physiopathology
Chronic Disease

@article {pmid40435383,
year = {2025},
author = {Nairn, B and Tsakanikas, V and Gordon, B and Karapintzou, E and Kaski, D and Fotiadis, DI and Bamiou, DE},
title = {Smart Wearable Technologies for Balance Rehabilitation in Older Adults at Risk of Falls: Scoping Review and Comparative Analysis.},
journal = {JMIR rehabilitation and assistive technologies},
volume = {12},
number = {},
pages = {e69589},
doi = {10.2196/69589},
pmid = {40435383},
issn = {2369-2529},
abstract = {BACKGROUND: Falls among older adults are a significant public health concern, often leading to severe injuries, decreased quality of life, and substantial health care costs. Smart wearable technologies for balance rehabilitation present a promising avenue for addressing the falls epidemic, capable of providing detailed objective movement data, engaging visuals, and real-time feedback. With the recent and rapid evolution of innovative technologies, including artificial intelligence (AI), augmented reality (AR) or virtual reality (VR), and motion tracking, there is a need to evaluate the market to identify the most effective and accessible smart balance systems currently available.

OBJECTIVE: This study aims to evaluate the current landscape of smart wearable technology systems for balance rehabilitation in older adults at risk of falls. In addition, it aims to compare market-available systems to the telerehabilitation of balance clinical and economic decision support system (TeleRehab DSS), a recently developed smart balance system.

METHODS: A scoping review and strengths, weaknesses, opportunities, and threats (SWOT) analysis was completed, exploring the landscape of smart balance systems in older adults at risk of falls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, electronic databases PubMed, MEDLINE, and Cochrane were systematically searched for articles in English from July 1, 2014, to July 1, 2024. Gray literature searches of relevant institutions and web pages were also conducted. The database search and commercial systems were then compared against the TeleRehab DSS in a SWOT analysis.

RESULTS: The scoping review yielded 17 systems that met the inclusion criteria; 10 investigational systems and 7 commercially available systems. Out of 10 studies, only 1 reported the use of intelligent learning or AI, 8 studies reported the use of motion tracking, and 9 studies used virtual reality. Of the studies incorporating motion tracking, 3 provided feedback as either visual or auditory. All but 2 studies reported the use of gamification, and 7 studies incorporated balance exercises. In total, 2 studies reported remote delivery, with 5 being clinician-supervised and 4 providing a clinician report. The SWOT analysis of TeleRehab DSS against the 7 market-available smart balance systems revealed several unique advantages, including personalized therapy with AI-DSS, AR for real-world interaction, enhanced clinician involvement, and comprehensive data analytics.

CONCLUSIONS: The findings from this scoping review highlight the rapid evolution of smart balance systems, yet significant gaps remain in AI integration, remote accessibility, and clinician-driven data analytics. Despite limitations such as cost, accessibility, and user training requirements, TeleRehab DSS emerges as a significant innovation, addressing many of these gaps through AI-driven personalization, AR for real-world interaction, and real-time clinician monitoring. These features position it as a next-generation solution that aligns closely with the evolving needs of patients and clinicians. The results of this review provide valuable insights for future research, supporting the need for further validation studies and the development of more intelligent and accessible balance rehabilitation technologies.},
}

@article {pmid40431734,
year = {2025},
author = {Kim, DH and Kim, JH and Jeon, MT and Kim, KS and Kim, DG and Choi, IS},
title = {The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
doi = {10.3390/v17050724},
pmid = {40431734},
issn = {1999-4915},
support = {25-BR-02-03//Korea Brain Research Institute/ ; },
mesh = {Humans ; *DNA-Binding Proteins/metabolism/genetics ; *COVID-19/complications/metabolism/virology/pathology ; *SARS-CoV-2/physiology ; *Neurodegenerative Diseases/metabolism/virology/pathology/etiology ; Virus Replication ; Animals ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein of 43 kDa (TDP-43) are involved in these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins of SARS-CoV-2 have been shown to induce pathological changes in TDP-43 through its cleavage, aggregation, and mislocalization. SARS-CoV-2 infection can cause liquid-liquid phase separation and stress granule formation, which accelerate the condensation of TDP-43, resulting in host RNA metabolism disruption. TDP-43 has been proposed to interact with SARS-CoV-2 RNA, though its role in viral replication remains to be fully elucidated. This interaction potentially facilitates viral replication, while viral-induced oxidative stress and protease activity accelerate TDP-43 pathology. Evidence from both clinical and experimental studies indicates that SARS-CoV-2 infection may contribute to long-term neurological sequelae, including amyotrophic lateral sclerosis-like and frontotemporal dementia-like features, as well as increased phosphorylated TDP-43 deposition in the central nervous system. Biomarker studies further support the link between TDP-43 dysregulation and neurological complications of long-term effects of COVID-19 (long COVID). In this review, we presented a novel integrative framework of TDP-43 pathology, bridging a gap between SARS-CoV-2 infection and mechanisms of neurodegeneration. These findings underscore the need for further research to clarify the TDP-43-related neurodegeneration underlying SARS-CoV-2 infection and to develop therapeutic strategies aimed at mitigating long-term neurological effects in patients with long COVID.},
}

Humans
*DNA-Binding Proteins/metabolism/genetics
*COVID-19/complications/metabolism/virology/pathology
*SARS-CoV-2/physiology
*Neurodegenerative Diseases/metabolism/virology/pathology/etiology
Virus Replication
Animals

@article {pmid40431631,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Amato, AA and Argañaraz, GA and Argañaraz, ER},
title = {SARS-CoV-2 Spike Protein and Long COVID-Part 2: Understanding the Impact of Spike Protein and Cellular Receptor Interactions on the Pathophysiology of Long COVID Syndrome.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
doi = {10.3390/v17050619},
pmid = {40431631},
issn = {1999-4915},
mesh = {*Spike Glycoprotein, Coronavirus/metabolism/genetics ; Humans ; *COVID-19/virology/physiopathology/complications/metabolism ; *SARS-CoV-2/metabolism/genetics/physiology ; *Receptors, Virus/metabolism ; Protein Binding ; Post-Acute COVID-19 Syndrome ; },
abstract = {SARS-CoV-2 infection has had a significant impact on global health through both acute illness, referred to as coronavirus disease 2019 (COVID-19), and chronic conditions (long COVID or post-acute sequelae of COVID-19, PASC). Despite substantial advancements in preventing severe COVID-19 cases through vaccination, the rise in the prevalence of long COVID syndrome and a notable degree of genomic mutation, primarily in the S protein, underscores the necessity for a deeper understanding of the underlying pathophysiological mechanisms related to the S protein of SARS-CoV-2. In this review, the latest part of this series, we investigate the potential pathophysiological molecular mechanisms triggered by the interaction between the spike protein and cellular receptors. Therefore, this review aims to provide a differential and focused view on the mechanisms potentially activated by the binding of the spike protein to canonical and non-canonical receptors for SARS-CoV-2, together with their possible interactions and effects on the pathogenesis of long COVID.},
}

*Spike Glycoprotein, Coronavirus/metabolism/genetics
Humans
*COVID-19/virology/physiopathology/complications/metabolism
*SARS-CoV-2/metabolism/genetics/physiology
*Receptors, Virus/metabolism
Protein Binding
Post-Acute COVID-19 Syndrome

@article {pmid40431629,
year = {2025},
author = {de Melo, BP and da Silva, JAM and Rodrigues, MA and Palmeira, JDF and Saldanha-Araujo, F and Argañaraz, GA and Argañaraz, ER},
title = {SARS-CoV-2 Spike Protein and Long COVID-Part 1: Impact of Spike Protein in Pathophysiological Mechanisms of Long COVID Syndrome.},
journal = {Viruses},
volume = {17},
number = {5},
pages = {},
doi = {10.3390/v17050617},
pmid = {40431629},
issn = {1999-4915},
mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism ; *COVID-19/complications/virology/physiopathology/pathology ; *SARS-CoV-2/pathogenicity ; Post-Acute COVID-19 Syndrome ; },
abstract = {SARS-CoV-2 infection has resulted in more than 700 million cases and nearly 7 million deaths worldwide. Although vaccination efforts have effectively reduced mortality and transmission rates, a significant proportion of recovered patients-up to 40%-develop long COVID syndrome (LC) or post-acute sequelae of COVID-19 infection (PASC). LC is characterized by the persistence or emergence of new symptoms following initial SARS-CoV-2 infection, affecting the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Despite the broad range of clinical symptoms that have been described, the risk factors and pathogenic mechanisms behind LC remain unclear. This review, the first of a two-part series, is distinguished by the discussion of the role of the SARS-CoV-2 spike protein in the primary mechanisms underlying the pathophysiology of LC.},
}

Humans
*Spike Glycoprotein, Coronavirus/metabolism
*COVID-19/complications/virology/physiopathology/pathology
*SARS-CoV-2/pathogenicity
Post-Acute COVID-19 Syndrome

@article {pmid40430532,
year = {2025},
author = {Kell, DB and Pretorius, E and Zhao, H},
title = {A Direct Relationship Between 'Blood Stasis' and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {5},
pages = {},
doi = {10.3390/ph18050712},
pmid = {40430532},
issn = {1424-8247},
abstract = {'Blood stasis' (syndrome) (BSS) is a fundamental concept in Traditional Chinese Medicine (TCM), where it is known as Xue Yu (). Similar concepts exist in Traditional Korean Medicine ('Eohyul') and in Japanese Kampo medicine (Oketsu). Blood stasis is considered to underpin a large variety of inflammatory diseases, though an exact equivalent in Western systems medicine is yet to be described. Some time ago we discovered that blood can clot into an anomalous amyloid form, creating what we have referred to as fibrinaloid microclots. These microclots occur in a great many chronic, inflammatory diseases are comparatively resistant to fibrinolysis, and thus have the ability to block microcapillaries and hence lower oxygen transfer to tissues, with multiple pathological consequences. We here develop the idea that it is precisely the fibrinaloid microclots that relate to, and are largely mechanistically responsible for, the traditional concept of blood stasis (a term also used by Virchow). First, the diseases known to be associated with microclots are all associated with blood stasis. Secondly, by blocking red blood cell transport, fibrinaloid microclots provide a simple mechanistic explanation for the physical slowing down ('stasis') of blood flow. Thirdly, Chinese herbal medicine formulae proposed to treat these diseases, especially Xue Fu Zhu Yu and its derivatives, are known mechanistically to be anticoagulatory and anti-inflammatory, consistent with the idea that they are actually helping to lower the levels of fibrinaloid microclots, plausibly in part by blocking catalysis of the polymerization of fibrinogen into an amyloid form. We rehearse some of the known actions of the constituent herbs of Xue Fu Zhu Yu and specific bioactive molecules that they contain. Consequently, such herbal formulations (and some of their components), which are comparatively little known to Western science and medicine, would seem to offer the opportunity to provide novel, safe, and useful treatments for chronic inflammatory diseases that display fibrinaloid microclots, including Myalgic Encephalopathy/Chronic Fatigue Syndrome, long COVID, and even ischemic stroke.},
}

@article {pmid40430160,
year = {2025},
author = {Caliman-Sturdza, OA and Gheorghita, RE and Soldanescu, I},
title = {Vitamin D and COVID-19: Clinical Evidence and Immunological Insights.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/life15050733},
pmid = {40430160},
issn = {2075-1729},
abstract = {Vitamin D has emerged as a potential modulator of immune responses, sparking interest in its role in COVID-19 susceptibility and clinical outcomes. This review synthesizes current clinical evidence and explores immunological insights into the relationship between vitamin D levels and COVID-19 infection severity. Epidemiological studies indicate an inverse correlation between vitamin D deficiency and an increased risk of severe disease, hospitalization, and mortality in COVID-19 patients. Immunologically, vitamin D exerts regulatory effects on both innate and adaptive immunity, enhancing antimicrobial defense mechanisms, reducing excessive inflammatory responses, and potentially mitigating cytokine storm events observed in severe COVID-19 cases. Despite promising observational data, clinical trials evaluating vitamin D supplementation have shown mixed results, underscoring the need for standardized dosing regimens and patient stratification. Future research should focus on large-scale randomized controlled trials to conclusively determine the therapeutic potential and optimal supplementation strategies for vitamin D in managing COVID-19.},
}

@article {pmid40416618,
year = {2025},
author = {Eltayeb, A and Adilović, M and Golzardi, M and Hromić-Jahjefendić, A and Rubio-Casillas, A and Uversky, VN and Redwan, EM},
title = {Intrinsic factors behind long COVID: exploring the role of nucleocapsid protein in thrombosis.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e19429},
pmid = {40416618},
issn = {2167-8359},
mesh = {Humans ; *COVID-19/complications ; *Thrombosis/virology/metabolism/etiology ; *SARS-CoV-2 ; *Coronavirus Nucleocapsid Proteins/metabolism ; },
abstract = {COVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammation and cause acute lung injury, the specific effects of the SARS-CoV-2 NP on host cells remain largely unexplored. Recent findings suggest that the NP acts as a pathogen-associated molecular pattern (PAMP) that binds to Toll-like receptor 2 (TLR2), activating NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. This activation is particularly pronounced in severe COVID-19 cases, leading to elevated levels of soluble ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), which contribute to endothelial dysfunction and multiorgan damage. Furthermore, the NP is implicated in hyperinflammation and thrombosis-key factors in COVID-19 severity and long COVID. Its potential to bind with MASP-2 (mannan-binding lectin serine protease 2) may also be linked to persistent symptoms in long COVID patients. Understanding these mechanisms, particularly the role of the NP in thrombosis, is essential for developing targeted therapies to manage both acute and chronic effects of COVID-19 effectively. This comprehensive review aims to elucidate the multifaceted roles of the NP, highlighting its contributions to viral pathogenesis, immune evasion, and the exacerbation of thrombotic events, thereby providing insights into potential therapeutic targets for mitigating the severe and long-term impacts of COVID-19.},
}

Humans
*COVID-19/complications
*Thrombosis/virology/metabolism/etiology
*SARS-CoV-2
*Coronavirus Nucleocapsid Proteins/metabolism

@article {pmid40416015,
year = {2025},
author = {Harabuchi, Y and Kumai, T and Nishi, K and Tanaka, A and Hotta, O and Hagino, H and Kusuyama, T and Mogitate, M and Ohno, Y and Sakakibara, A and Araki, S and Nishida, Y and Shintani, T and Takezawa, H and Ito, H and Komazawa, D and Nishiwaki, N and Toritani, R and Hirahata, K and Marumo, S},
title = {Retracted: Chronic Epipharyngitis Treated with Epipharyngeal Abrasion Therapy: Symptoms, Diagnosis, Pathogenesis, and Treatment Outcomes.},
journal = {JMA journal},
volume = {8},
number = {2},
pages = {371-384},
pmid = {40416015},
issn = {2433-3298},
abstract = {Chronic epipharyngitis is associated with a wide variety of symptoms, including local symptoms such as postnasal drip, sore throat, lump sensation of the pharynx, headache, chronic cough, nasal obstruction, tinnitus/ear fullness, chronic phlegm and dysphonia due to inflammation of the epipharynx, functional somatic symptoms such as chronic fatigue, dizziness, insomnia, brain fog, abdominal discomfort, and depression caused by dysfunction of the hypothalamus-limbic system via disturbances of vagal response and cerebrospinal fluid outflow, and distant organ symptoms such as immunoglobulin A nephropathy and palmoplantar pustulosis caused by the epipharyngeal lymphoid tissue as an etiologic organ. In the past, chronic inflammation in the epipharynx was difficult to prove by gross findings, now, direct observation of the epipharyngeal inflammation by endoscopy has become easier for the diagnosis. For the treatment of chronic epipharyngitis, epipharyngeal abrasive therapy (EAT), epipharyngeal application of a 1% zinc chloride solution intranasally or orally was popular since the 1960s, recently, endoscopic EAT (E-EAT), in which epipharynx is safely and accurately observed and abraded under clear vision using an endoscope, has been developed. The mechanisms of EAT effects can be classified into anti-inflammatory/antiviral effect, bloodletting effect, and vagus nerve stimulation effect. Recently, the effectiveness of EAT for post-acute sequelae of coronavirus disease 2019 (COVID-19), known as long COVID, has come into the limelight, and the number of patients for whom EAT is expected to increase. In 2019, the Japan Society of Stomato-pharyngology established the EAT Review Committee to accumulate evidence on the efficacy of EAT and to establish indications and techniques for its use. In this article, the EAT Review Committee outlines its symptoms, pathogenesis, and diagnosis of chronic epipharyngitis, technique of E-EAT, mechanisms of EAT effects, past reports for the efficacy of EAT, and a multicenter prospective study.},
}

@article {pmid40415285,
year = {2025},
author = {Eltayeb, A and Rubio-Casillas, A and Uversky, VN and Redwan, EM},
title = {Intrinsic Factors Behind Long COVID: VI. Combined Impact of G3BPs and SARS-CoV-2 Nucleocapsid Protein on the Viral Persistence and Long COVID.},
journal = {Journal of cellular biochemistry},
volume = {126},
number = {5},
pages = {e70038},
doi = {10.1002/jcb.70038},
pmid = {40415285},
issn = {1097-4644},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *COVID-19/virology/metabolism/immunology/pathology ; *SARS-CoV-2/metabolism/physiology ; *Coronavirus Nucleocapsid Proteins/metabolism ; *RNA Recognition Motif Proteins/metabolism/immunology ; *Poly-ADP-Ribose Binding Proteins/metabolism/immunology ; *DNA Helicases/metabolism ; *Phosphoproteins/metabolism ; *RNA Helicases/metabolism ; Virus Replication ; Stress Granules/metabolism/virology ; Host-Pathogen Interactions ; },
abstract = {The efficient transmission of SARS-CoV-2 caused the COVID-19 pandemic, which affected millions of people around the globe. Despite extensive efforts, specific therapeutic interventions and preventive measures against COVID-19 and its consequences, such as long COVID, have not yet been identified due to the lack of a comprehensive knowledge of the SARS-CoV-2 biology. Therefore, a deeper understanding of the sophisticated strategies employed by SARS-CoV-2 to bypass the host antiviral defense systems is needed. One of these strategies is the inhibition of the Ras GTPase-activating protein-binding protein (GAP SH3-binding protein or G3BP)-dependent host immune response by the SARS-CoV-2 nucleocapsid (N) protein. This inhibition disrupts the formation of stress granules (SGs), which are crucial for antiviral defense. By preventing SG formation, the virus enhances its replication and evades the host's immune response, leading to increased disease severity. Given the involvement of G3BP1 in SG formation and its ability to interact with viral proteins, along with the crucial role of the N protein in the replication of the virus, we hypothesize that these proteins may have a potential role in the pathogenesis of long COVID. Despite the current lack of direct evidence linking these proteins to long COVID, their interactions and functions suggest a possible connection that warrants further investigation.},
}

Humans
*COVID-19/virology/metabolism/immunology/pathology
*SARS-CoV-2/metabolism/physiology
*Coronavirus Nucleocapsid Proteins/metabolism
*RNA Recognition Motif Proteins/metabolism/immunology
*Poly-ADP-Ribose Binding Proteins/metabolism/immunology
*DNA Helicases/metabolism
*Phosphoproteins/metabolism
*RNA Helicases/metabolism
Virus Replication
Stress Granules/metabolism/virology
Host-Pathogen Interactions

@article {pmid40412913,
year = {2025},
author = {DeMasi, M and Bujold, L},
title = {Effect of the Covid Pandemic on Women's Health.},
journal = {Primary care},
volume = {52},
number = {2},
pages = {371-382},
doi = {10.1016/j.pop.2025.01.009},
pmid = {40412913},
issn = {1558-299X},
mesh = {Humans ; *COVID-19/epidemiology ; Female ; *Women's Health ; United States/epidemiology ; SARS-CoV-2 ; Pandemics ; },
abstract = {The corona virus disease 2019 (COVID-19) pandemic impacted all spheres of the lives of women. This article focuses on the impact on the health, careers, and family lives of women in the United States. There is a lasting impact from COVID-19 on the lives and health of women. Preventative care and chronic care were disrupted. Long covid seems to impact premenopausal women at much higher rates than men. Time spent between work and home changed for many during the pandemic. Women shifted to more time spent on home duties. The long-term outcome of career advancement and economic success is unknown.},
}

Humans
*COVID-19/epidemiology
Female
*Women's Health
United States/epidemiology
SARS-CoV-2
Pandemics

@article {pmid40407658,
year = {2025},
author = {Park, SO and Nanda, N},
title = {Long COVID: A Systematic Review of Preventive Strategies.},
journal = {Infectious disease reports},
volume = {17},
number = {3},
pages = {},
doi = {10.3390/idr17030056},
pmid = {40407658},
issn = {2036-7430},
abstract = {Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, long COVID (LC) has become a significant global health burden. While knowledge about LC is accumulating, studies on its prevention are still lacking. Methods: We conducted a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to investigate prevention options for LC. We identified fifteen articles on vaccines, seven on antivirals, and six on other interventions after searching for articles in the PubMed/MEDLINE database using the MeSH terms. Results: Most vaccine-related studies demonstrated a protective effect of COVID-19 vaccines against developing LC. Our review found an equivocal effect of antivirals, while metformin had a protective effect in outpatients and corticosteroids were protective in hospitalized patients against LC. Conversely, COVID-19 convalescent plasma and multiple micronutrient supplement did not confer any protection against LC. Conclusions: COVID-19 vaccination is vital as it not only prevents COVID-19 but also reduces the severity of illness and may help prevent LC. Further studies are warranted to shed light on preventive strategies for long COVID.},
}

@article {pmid40405092,
year = {2025},
author = {Seo, YB and Choi, YJ and Seo, JW and Kim, EJ and Lee, J and Song, JY},
title = {Therapeutic options for the treatment of post-acute sequelae of COVID-19: a scoping review.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {731},
pmid = {40405092},
issn = {1471-2334},
support = {HD22C2045//Korea Health Industry Development Institute/Republic of Korea ; },
mesh = {Humans ; *COVID-19/complications/therapy ; Antiviral Agents/therapeutic use ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *COVID-19 Drug Treatment ; Hyperbaric Oxygenation ; },
abstract = {OBJECTIVES: This scoping review aimed to summarize the available studies to address the question of which therapeutic agents can be utilized for patients with post-acute sequelae of COVID-19 (PASC).

METHODS: We conducted a systematic search in medical databases, including PubMed and Embase, for studies aligned with our objectives published between January 1, 2020, and July 22, 2024. For each study, we summarized the main symptoms targeted, study design, therapeutic regimens, evaluation tools, and clinical outcomes.

RESULTS: A total of 413 studies were identified, and 39 studies were included in this review based on relevance to the research objectives. We primarily focused on high-level evidence studies, such as meta-analyses and randomized controlled trials, but observational studies were included when evidence was scarce. Therapeutic agents evaluated included hyperbaric oxygen, ivermectin, metformin, naltrexone, micronutrient supplements, antifibrotic agents, antiviral agents, and selective serotonin reuptake inhibitors (SSRIs). Among these, hyperbaric oxygen, antifibrotic agents, antiviral agents, and SSRIs demonstrated promising results. However, the heterogeneity of PASC symptoms posed challenges in synthesizing findings for specific symptom-based outcomes.

CONCLUSION: Given the heterogeneity of symptoms, this review highlights the need for standardized and targeted research to better address the diverse therapeutic needs of patients with PASC.

CLINICAL TRIAL: Not applicable.},
}

Humans
*COVID-19/complications/therapy
Antiviral Agents/therapeutic use
SARS-CoV-2
Post-Acute COVID-19 Syndrome
*COVID-19 Drug Treatment
Hyperbaric Oxygenation

@article {pmid40400892,
year = {2025},
author = {Ferrer, G and Valerio-Pascua, F and Alas-Pineda, C and Gaitán-Zambrano, K and Pavón-Varela, DJ},
title = {Intranasal Chlorpheniramine for Early Symptomatic Treatment of COVID-19 and the Impact on Long-COVID.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82736},
pmid = {40400892},
issn = {2168-8184},
abstract = {This review explores the therapeutic potential of intranasal chlorpheniramine maleate (iCPM) in managing both acute COVID-19 and Long COVID by integrating histamine H1 receptor antagonism and bitter taste receptor (T2R) activation. Current literature on histamine-mediated inflammation, T2R activation, and the dual-action mechanisms of iCPM were analyzed. Emphasis was placed on its antiviral, anti-inflammatory, and mucosal immunity-enhancing properties. iCPM demonstrates significant efficacy in addressing acute COVID-19 symptoms by inhibiting histamine-mediated inflammatory pathways and reducing cytokine storms. As a T2R agonist, it enhances mucosal immunity through nitric oxide production, mucociliary clearance, and antimicrobial peptide synthesis, reducing viral replication and supporting respiratory health. Additionally, iCPM shows promise in mitigating persistent symptoms of long COVID, including fatigue, brain fog, and respiratory dysfunction, by addressing chronic inflammation and residual viral activity. The integration of H1 receptor antagonism and T2R activation positions iCPM as a novel dual-target therapy for respiratory infections. Its localized delivery and broad mechanism of action make it a promising candidate for managing both the acute and chronic phases of COVID-19. Future research should focus on large-scale clinical trials and personalized approaches based on genetic variations in T2R pathways.},
}

@article {pmid40391044,
year = {2025},
author = {Duenas, K and Chwa, WJ and Hoque, F},
title = {Overview of Long COVID: Navigating the Aftermath.},
journal = {Journal of Brown hospital medicine},
volume = {4},
number = {2},
pages = {133879},
pmid = {40391044},
issn = {2994-5593},
abstract = {The coronavirus disease (COVID-19) pandemic was a global health crisis with far-reaching consequences. Among these were physical and mental health complications that emerged weeks or even months after the initial COVID-19 infection, collectively termed "long COVID" or "post-COVID syndrome." Identifying the epidemiology, risk factors, clinical manifestations, and management strategies for long COVID is crucial for both clinicians and patients, which is the focus of this review. The prevalence of long COVID varies across studies, generally ranging from 5% to 20%. Prominent risk factors include female sex, older age, a high number of acute symptoms, lower socioeconomic status, and underlying comorbidities such as diabetes, asthma, or chronic obstructive pulmonary disease. The clinical manifestations of long COVID are diverse; beyond the commonly reported symptoms of fatigue, malaise, ageusia, and anosmia, neuropsychiatric complications such as headache, cognitive deficits, and depression are also potential outcomes. Although there is currently no consensus on the management of long COVID, multidisciplinary care teams with appropriate referrals and follow-up diagnostic studies are essential in evaluating the clinical course of long COVID patients.},
}

@article {pmid40389117,
year = {2025},
author = {Rudroff, T},
title = {Climate crossroads: How global warming drives coronavirus emergence, the long COVID crisis of tomorrow, and AI's role in navigating our future.},
journal = {Infectious diseases now},
volume = {},
number = {},
pages = {105091},
doi = {10.1016/j.idnow.2025.105091},
pmid = {40389117},
issn = {2666-9919},
abstract = {This narrative review examines the critical nexus between climate change, coronavirus emergence, and Long COVID-a triad that may shape public health outcomes for generations. Climate change disrupts ecological balances that have historically limited viral spillover events, creating novel interfaces between wildlife reservoirs and human populations. The coronavirus family presents particular concern due to its diversity, adaptability, and demonstrated capacity for cross-species transmission. With over 200 coronaviruses identified in bat populations alone, this vast reservoir of genetic diversity, combined with the family's propensity for recombination, creates substantial pandemic potential that climate disruption may further amplify. Long COVID has revealed another dimension of the coronavirus threat: the potential for significant chronic disease burden following acute infection. This complex multisystem condition affects a substantial portion of SARS-CoV-2 infected individuals, with mechanisms including viral persistence, autoimmunity, microclot formation, and mitochondrial dysfunction. Future projections suggest that climate change could increase global viral spillover risk by 30-45% by 2070, particularly in Southeast Asia, Central Africa, and parts of South America. Artificial intelligence offers promising tools for addressing these interconnected challenges through enhanced surveillance, accelerated therapeutic development, and optimized healthcare delivery. Understanding the climate-coronavirus-chronic illness nexus has become essential to the development of resilient health systems and effective planetary health policies face to an uncertain future.},
}

@article {pmid40385588,
year = {2025},
author = {Ranque, B and Cogan, E},
title = {Internal medicine at the crossroads of long COVID diagnosis and management.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1521472},
pmid = {40385588},
issn = {2296-858X},
abstract = {The lack of specificity in its definition is a major obstacle to both explanatory and therapeutic research in long COVID. It brings together, on the one hand, patients with severe COVID-19 who suffer the classic complications of prolonged hospitalization and decompensation of comorbidities and, on the other hand, patients with non-severe acute COVID-19 who report multiple symptoms that cannot be fully explained by a biomechanical model. Indeed, despite numerous studies, it remains unclear how persistent viral infection, immunological or coagulation disturbances may contribute mechanistically to long COVID. Nevertheless, internal medicine should be in good place to manage these patients. Indeed, the diversity of symptoms may evoke a broad spectrum of differential diagnoses that are familiar to internists. Their experience in the exploration of unexplained symptoms is also valuable. It can reduce the need for multiple consultations with specialists and unnecessary laboratory or imaging tests. However, long COVID diagnosis cannot be limited to the exclusion of all other conditions one by one. An open and non-dualistic approach is required to identify other mechanisms that may explain the symptoms. Based on their clinical experience, most French internists who responded to an opinion survey consider that long COVID corresponds most closely to a functional somatic disorder (FSD) and seek the help of specialists in mental health care to assist in the management of the patients in a multi-disciplinary approach. However, as with other FSDs, patients with long COVID are usually reluctant to be managed by mental health care specialists, given the very physical nature of their presentation. Unfortunately, most physicians are in turn reluctant to take care of them, due to poor knowledge about FSD, leading to management failure. Alternatively, a comprehensive multidisciplinary care orchestrated by an experienced internist is generally well-accepted. It includes providing rational cognitive explanations for the symptoms and support for behavioral changes tailored to the patient. While waiting for hypothetical randomized controlled trials assessing drugs with positive results, such a holistic approach has been successfully applied in many individuals with severe long COVID. However, its generalization would require a much broader training for FSD of all health care providers.},
}

@article {pmid40384184,
year = {2025},
author = {N, SR and Choi, G and Jin, GW and Choy, JH},
title = {Transforming Niclosamide through Nanotechnology: A Promising Approach for Long COVID Management.},
journal = {Small (Weinheim an der Bergstrasse, Germany)},
volume = {},
number = {},
pages = {e2410345},
doi = {10.1002/smll.202410345},
pmid = {40384184},
issn = {1613-6829},
support = {//National Academy of Sciences, Republic of Korea/ ; },
abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over 770 million people worldwide. The long-term effects of COVID-19 and their management have become important issues. Accumulating evidence indicates that post-COVID-19 syndrome, also known as long COVID, is not limited to respiratory symptoms but affects a wide range of systems, including neurological, cardiovascular, gastrointestinal, musculoskeletal, and reproductive systems etc. The social and economic losses associated with these effects are estimated to reach 3·7 trillion dollars in the United States alone. However, no treatment for long COVID has been developed. Herein, the literature on long COVID is comprehensively reviewed to examine the underlying causes. Additionally, evidence supporting the efficacy of nanoengineered niclosamide is presented, given its ability to counteract the underlying causes. Niclosamide is already Food and Drug Administration (FDA)-approved, and the nanoengineered one is a viable candidate for clinical trials for long COVID.},
}

@article {pmid40105889,
year = {2025},
author = {Mueller, MR and Ganesh, R and Beckman, TJ and Hurt, RT},
title = {Long COVID: emerging pathophysiological mechanisms.},
journal = {Minerva medica},
volume = {116},
number = {2},
pages = {156-165},
doi = {10.23736/S0026-4806.25.09539-4},
pmid = {40105889},
issn = {1827-1669},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Fatigue/physiopathology/etiology ; },
abstract = {Post-COVID conditions, also termed "long COVID," are a heterogeneous set of conditions persisting greater than 28 days after initial infection. These conditions, which include fatigue, brain fog, orthostatic intolerance, and pain, are a significant source of morbidity and limited function worldwide. Nonetheless, both the pathophysiology and treatment of long COVID remain poorly understood. Several pathophysiologic mechanisms have been proposed including neuroinflammatory drivers, endothelial dysfunction, neurotransmitter dysregulation, mitochondrial dysfunction, autonomic dysfunction, and central sensitization. In this article, we present a conceptual framework for evaluation of long COVID symptoms, as well as the evidence behind their proposed pathophysiologic mechanisms. Patients may struggle with one or more of the proposed mechanisms listed above, and the contributions from each process may vary depending on the patient. Although no FDA-approved therapies exist for long COVID, we review several potential promising and mechanistically plausible therapies.},
}

Humans
*COVID-19/physiopathology/complications
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Fatigue/physiopathology/etiology

@article {pmid40375203,
year = {2025},
author = {Vallée, A and Arutkin, M and Ceccaldi, PF and Feki, A and Ayoubi, JM},
title = {Long COVID and endometriosis: a systematic review and meta-analysis.},
journal = {BMC women's health},
volume = {25},
number = {1},
pages = {229},
pmid = {40375203},
issn = {1472-6874},
mesh = {Humans ; *Endometriosis/epidemiology/complications ; Female ; *COVID-19/epidemiology/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; },
abstract = {Long COVID conditions entail the persistence of COVID-19-related symptoms for at least eight weeks following SARS-CoV-2 infection. The prevalence of long COVID is estimated to range from 10 to 30% among individuals infected with SARS-CoV-2. Despite its growing impact on healthcare systems, long COVID remains poorly understood. In parallel, endometriosis, a chronic inflammatory condition affecting around 10% of reproductive-age women, is marked by symptoms such as pelvic pain and infertility. The aim of this study was to assess the association between endometriosis and long COVID. We performed a systematic review of long COVID among endometriosis patients in Pubmed/Medline, Cochran Library and Science Direct databases from inception to August 2023. We independently selected studies, extracted data, assessed risk of bias, and compared endometriosis versus non endometriosis patients for long. Pooled analyses were based on random-effect models, and the I[2] statistic was used to quantify heterogeneity across studies. A total of 2 cross-sectional studies (N = 216,095 participants) were included. The pooled analysis comparing endometriosis to non-endometriosis patients significantly showed association for long COVID (pooled RR = 1.41 [1.31-1.52], I[2] = 29%, p < 0.001). Women, who are disproportionately affected by long COVID, particularly those with endometriosis, may face compounded health challenges. While our findings suggest a possible association between endometriosis and long COVID, the evidence is currently limited to two observational studies. Further research involving diverse populations and robust study designs is needed to confirm this relationship and clarify underlying mechanisms.},
}

Humans
*Endometriosis/epidemiology/complications
Female
*COVID-19/epidemiology/complications
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Prevalence

@article {pmid40366711,
year = {2025},
author = {Vu, PD and Abdi, S},
title = {Post-acute sequelae SARS-CoV-2 infection and neuropathic pain: a narrative review of the literature and future directions.},
journal = {Pain management},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/17581869.2025.2501521},
pmid = {40366711},
issn = {1758-1877},
abstract = {PURPOSE OF REVIEW: Neuropathic pain is a recognized and debilitating symptom of SARS-CoV-2 infection across acute, post-acute, and long-COVID phases. Initially emerging as acute or subacute symptoms, these neuropathic manifestations can evolve into chronic conditions, with approximately 10% of all SARS-CoV-2 cases (estimated 65 million individuals globally) developing post-acute SARS-CoV-2 (PASC) neuropathic sequalae. Given the limited literature specifically addressing neuropathic pain related to PASC, a deeper understanding is needed to improve management and reduce patient burden.

RECENT FINDINGS: PASC symptoms are associated with disease severity, elevated body mass indexes, preexisting psychological conditions, and addiction history. Sex differences appear to influence prevalence, and the multisystem nature of PASC complicates symptom presentation, with mood disorders, fatigue, and cognitive dysfunction contributing to altered pain perception. Proposed mechanisms include immune dysregulation, persistent viral protein effects, and neuroanatomical changes. Management typically involves a multimodal approach.

SUMMARY: This review examines SARS-CoV-2 neuropathic pain across the illness trajectory, examining its pathophysiology, prevalence, and treatment. It highlights the potential for subacute neuropathic symptoms to become chronic and calls for future research to refine long-term management strategies and assess broader healthcare implications.},
}

@article {pmid40364149,
year = {2025},
author = {Brewer, KD and Santo, NV and Samanta, A and Nag, R and Trotsyuk, AA and Rajadas, J},
title = {Advances in Therapeutics for Chronic Lung Diseases: From Standard Therapies to Emerging Breakthroughs.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/jcm14093118},
pmid = {40364149},
issn = {2077-0383},
abstract = {Background: The global health burden of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS) affects billions of people and is associated with high levels of healthcare expenditure. Conventional therapies (bronchodilators and corticosteroids) provide symptomatic benefit but take no effect on disease progression, demonstrating the need to develop new therapies. Emerging therapies treat the underlying mechanisms of these chronic diseases, which provide symptomatic relief and benefit the underlying disease. Methods: This review assesses the evolution of therapeutic interventions for chronic lung diseases from a series of established inhaled combination therapies to biologics, gene therapy, and even AI-based stratification of therapies for patients. In addressing these issues, we review the mechanisms of action, evidence of efficacy, and clinical trial evidence, while discussing access issues affecting the implementation of these therapies and ethical issues in relation to their use. Results: The review highlights recent developments in treatment approaches, such as gene therapies aimed at cystic fibrosis mutations, advanced drug delivery pathways for more accurate targeting, and stem cell-based therapies designed to replace damaged lung tissue. These developments have the potential to improve outcomes for chronic lung diseases, but the challenges, including a lack of access, adequate patient selection, and long-term safety, need to be addressed. Conclusions: New therapies offer tremendous potential, but their transition from laboratory to clinic still face numerous barriers including access, regulation, and a need for personalized therapy approaches. The review indicates that future research should develop strategies to reduce barriers to access, improve distribution, and improve clinical guidelines to successfully implement these new therapies.},
}

@article {pmid40364089,
year = {2025},
author = {Moustakli, E and Stavros, S and Michaelidis, TM and Potiris, A and Christodoulaki, C and Zachariou, A and Drakakis, P and Zikopoulos, K and Domali, E and Zikopoulos, A},
title = {Long-Term Effects of COVID-19 on Women's Reproductive Health and Its Association with Autoimmune Diseases, Including Multiple Sclerosis.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/jcm14093057},
pmid = {40364089},
issn = {2077-0383},
abstract = {Concern over COVID-19's long-term influence on women's reproductive health is growing, with emerging research suggesting potential links to ovarian dysfunction, menstrual irregularities, fertility challenges, and adverse pregnancy outcomes. Post-viral immune dysregulation is linked to both the development and exacerbation of autoimmune diseases, including multiple sclerosis (MS). Long COVID has been associated with immunological dysfunction, hormonal imbalances, and chronic inflammation, all of which may worsen autoimmune disorders and reproductive health issues. Long COVID is characterized by symptoms persisting for weeks or months beyond the acute infection phase. There are indications that prolonged COVID may contribute to autoimmune disease development through mechanisms such as immune hyperactivation, molecular mimicry, and dysregulated cytokine responses. Although this research field is still emerging, growing evidence suggests that SARS-CoV-2 infection may have lasting effects on women's health, highlighting the need for further studies into its underlying mechanisms and long-term clinical outcomes. This review compiles recent findings on the long-term impact of COVID-19 on women's reproductive health and its potential association with autoimmune disorders, particularly MS.},
}

@article {pmid40335476,
year = {2025},
author = {O'Mahoney, LL and Routen, A and Gillies, C and Jenkins, SA and Almaqhawi, A and Ayoubkhani, D and Banerjee, A and Brightling, C and Calvert, M and Cassambai, S and Ekezie, W and Funnell, MP and Welford, A and Peace, A and Evans, RA and Jeffers, S and Kingsnorth, AP and Pareek, M and Seidu, S and Wilkinson, TJ and Willis, A and Shafran, R and Stephenson, T and Sterne, J and Ward, H and Ward, T and Khunti, K},
title = {The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4249},
pmid = {40335476},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/epidemiology/complications/physiopathology/virology ; *Post-Acute COVID-19 Syndrome/epidemiology/physiopathology/virology ; Risk Factors ; SARS-CoV-2/pathogenicity ; },
abstract = {The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group. Results were summarised descriptively and meta-analyses were conducted to derive pooled risk ratio estimates. 50 studies totaling 14,661,595 people were included. In all populations combined, there was an increased risk of a wide range of 39 out of 40 symptoms in those infected with SARS‑CoV‑2 compared to uninfected controls. The symptoms with the highest pooled relative risks were loss of smell (RR 4.31; 95% CI 2.66, 6.99), loss of taste (RR 3.71; 95% CI 2.22, 7.26), poor concentration (RR 2.68; 95% CI 1.66, 4.33), impaired memory (RR 2.53; 95% CI 1.82, 3.52), and hair loss/alopecia (RR 2.38; 95% CI 1.69, 3.33). This evidence synthesis, of 50 controlled studies with a cumulative participant count exceeding 14 million people, highlights a significant risk of diverse long-term symptoms in individuals infected with SARS-CoV-2, especially among those who were hospitalised.},
}

Humans
*COVID-19/epidemiology/complications/physiopathology/virology
*Post-Acute COVID-19 Syndrome/epidemiology/physiopathology/virology
Risk Factors
SARS-CoV-2/pathogenicity

@article {pmid40330025,
year = {2025},
author = {Smail, SW and Albarzinji, N and Salih, RH and Taha, KO and Hirmiz, SM and Ismael, HM and Noori, MF and Azeez, SS and Janson, C},
title = {Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1537456},
pmid = {40330025},
issn = {2235-2988},
mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *COVID-19/microbiology/physiopathology/therapy/complications ; *SARS-CoV-2 ; *Gastrointestinal Microbiome ; },
abstract = {The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), in late 2019 initiated a global health crisis marked by widespread infection, significant mortality, and long-term health implications. While SARS-CoV-2 primarily targets the respiratory system, recent findings indicate that it also significantly disrupts the human microbiome, particularly the gut microbiota, contributing to disease severity, systemic inflammation, immune dysregulation, and increased susceptibility to secondary infections and chronic conditions. Dysbiosis, or microbial imbalance, exacerbates the clinical outcomes of COVID-19 and has been linked to long-COVID, a condition affecting a significant proportion of survivors and manifesting with over 200 symptoms across multiple organ systems. Despite the growing recognition of microbiome alterations in COVID-19, the precise mechanisms by which SARS-CoV-2 interacts with the microbiome and influences disease progression remain poorly understood. This narrative review investigates the impact of SARS-CoV-2 on host-microbiota dynamics and evaluates its implications in disease severity and for developing personalized therapeutic strategies for COVID-19. Furthermore, it highlights the dual role of the microbiome in modulating disease progression, and as a promising target for advancing diagnostic, prognostic, and therapeutic approaches in managing COVID-19.},
}

Humans
*Dysbiosis/microbiology/therapy
*COVID-19/microbiology/physiopathology/therapy/complications
*SARS-CoV-2
*Gastrointestinal Microbiome

@article {pmid40326310,
year = {2025},
author = {El-Naas, A and Hamad, O and Nair, S and Alfakhri, B and Mahmoud, S and Haji, A and Ahmed, L and Lebbe, A and Aboulwafa, A and Shaikh, F and Bouhali, I and Zakaria, D},
title = {New Onset of Type 1 and Type 2 Diabetes Post-COVID-19 Infection: A Systematic Review.},
journal = {Emerging microbes & infections},
volume = {},
number = {},
pages = {2492211},
doi = {10.1080/22221751.2025.2492211},
pmid = {40326310},
issn = {2222-1751},
abstract = {AbstractCOVID-19 may primarily cause respiratory symptoms but can lead to long-term effects known as long COVID. COVID-19-induced diabetes mellitus was reported in many patients which shares characteristics of types 1 and 2 (T1DM and T2DM). This study aims to identify and analyze the reported cases of new onset diabetes post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of T1DM or T2DM post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 43 studies met our inclusion criteria. Our results revealed that the overall prevalence of new onset diabetes post-COVID-19 was 1.37% with higher prevalence for T2DM (0.84%) as compared to T1DM (0.017%) while the type of diabetes was not reported in 0.51% of the cases. Several risk factors for developing diabetes post-COVID-19 infection were identified including the type of SARS-CoV-2 variant, age, comorbidities and the vaccination status. The direct viral attack of the pancreatic beta cells as well as inflammation and the anti-inflammatory corticosteroids were proposed as possible mechanisms of the COVID-19 induced diabetes. A multidisciplinary approach involving endocrinologists, primary care physicians, and infectious disease specialists should be implemented in the management of post-COVID patients to address both the acute and long-term complications, including metabolic changes and risk of diabetes.},
}

@article {pmid40322881,
year = {2025},
author = {Vieira Junior, JCA and Sander, MRL and Matos, JAO and Medeiros, AM and Silva, FSD and Aires, CAM},
title = {Neurological Post-Acute Sequelae of COVID-19 in Non-Hospitalized Patients: An Integrative Review.},
journal = {Biological research for nursing},
volume = {},
number = {},
pages = {10998004251335968},
doi = {10.1177/10998004251335968},
pmid = {40322881},
issn = {1552-4175},
abstract = {The COVID-19 pandemic has had a significant impact on the global population. The infection, caused by SARS-CoV-2, presents with a variety of clinical manifestations, from asymptomatic cases to more severe forms, including a variety of neurological symptoms, such as fatigue, weakness, brain fog, paresthesias, dysautonomia, anosmia, and dysgeusia. Additionally, the disease is associated with the long COVID syndrome, in which there is persistence of the effects and symptoms of the acute phase. In recent years the literature has shown relevant data on long COVID, but there is still a need to deepen the knowledge about these long term manifestations. Thus, the present study aimed to describe the main neurological sequelae resulting from SARS-CoV-2 infection in non-hospitalized population during the long phase of the disease, gathering scientific evidence through an integrative review of the prevalence of symptoms, patient profile, duration and severity of sequelae, risk factors, comorbidities, and possible nervous system structural damage. The PubMed/Medline database was used with descriptors and, at the end of the screening process with predefined inclusion and exclusion criteria, 22 studies were included. A group of neurological symptoms associated with long COVID was identified: myalgia, dysgeusia, memory alterations, olfactory dysfunction, dizziness, and pain. Most patients presented multiple symptoms that lasted for more than one year with a significant impact on quality of life. The main risk factors were dyslipidemia, age, ethnicity, muscle/ joint pain, and sex. This review highlights the importance of further studies on the syndrome, its etiology, diagnosis, follow-up, and treatments.},
}

@article {pmid40310228,
year = {2025},
author = {Bontempo, AC and Bontempo, JM and Duberstein, PR},
title = {Ignored, dismissed, and minimized: Understanding the harmful consequences of invalidation in health care-A systematic meta-synthesis of qualitative research.},
journal = {Psychological bulletin},
volume = {151},
number = {4},
pages = {399-427},
doi = {10.1037/bul0000473},
pmid = {40310228},
issn = {1939-1455},
support = {//U.S. Department of Health and Human Services; Health Resources and Services Administration/ ; },
mesh = {Humans ; Qualitative Research ; *Disease/psychology ; *Delivery of Health Care ; },
abstract = {The upsurge in the prevalence of contested, ambiguous, and difficult-to-diagnose illnesses presents challenges for clinicians who too often respond by invalidating patients' symptoms. Although numerous qualitative studies have reported the effects of invalidation on patients' psychological and behavioral outcomes, this body of research has not been systematically reviewed. Informed by Linehan's (1993) conceptualization of invalidation, this systematic review elucidated the negative consequences, of symptom invalidation, or the dismissal or minimization of a person's experiences with illness. We reviewed 151 qualitative reports representing 11,307 individuals with Ehlers-Danlos syndrome, endometriosis, fibromyalgia syndrome, Gulf War syndrome, irritable bowel syndrome, long COVID, multiple chemical sensitivity, myalgic encephalomyelitis/chronic fatigue syndrome, postural orthostatic tachycardia syndrome, systemic lupus erythematosus, and vulvodynia. Consistent with Linehan's theorizing, thematic analysis identified four broad classes of consequences: induced emotional states and beliefs (e.g., shame, suicidality), induced health care emotional states and beliefs (e.g., health care-related anxiety and trauma), induced health care behavior (e.g., health care system avoidance), and diagnostic delay. Informed by these findings, we developed a novel conceptual model explaining how symptom invalidation leads to these consequences and thereby undermines health outcomes. Future work should explore the proposed conceptual model and identify theoretically informed interventions and policies aimed at preventing symptom invalidation to improve psychological, behavioral, and health outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}

Humans
Qualitative Research
*Disease/psychology
*Delivery of Health Care

@article {pmid40305533,
year = {2025},
author = {Wang, R and Lin, M and Yu, S and Xue, X and Hu, X and Wang, Z},
title = {Predictors of post-COVID-19 syndrome: a meta-analysis.},
journal = {Journal of infection in developing countries},
volume = {19},
number = {4},
pages = {490-497},
doi = {10.3855/jidc.18574},
pmid = {40305533},
issn = {1972-2680},
mesh = {Female ; Humans ; Male ; Comorbidity ; *COVID-19/complications/diagnosis/epidemiology/virology ; Dyspnea/diagnosis/epidemiology/virology ; *Post-Acute COVID-19 Syndrome/diagnosis/epidemiology/virology ; Prognosis ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Sex Factors ; },
abstract = {INTRODUCTION: Post Coronavirus Disease 2019 (COVID-19) Syndrome also known as long COVID-19 would affect survivors of various patients. At present, the evidence for predicting a poor prognosis of COVID-19 remains insufficient. This study aims to explore potential predictors of post-COVID-19 syndrome.

METHODOLOGY: A systematic review process and meta-analysis method are applied to identify the predictors. Systematic searches were conducted without language restrictions from December 1, 2019, to February 28, 2022, on PubMed, Embase, Google Scholar, Web of Science, and Cochrane Library using specific keywords relevant to our targets. The Newcastle Ottawa Scale observational research tool was used to assess study quality and the R (4.1.1) package meta was used for statistical analysis.

RESULTS: Our meta-analysis of 14 studies showed that females (OR = 1.42, 95% CI: 1.19-1.70), the severity of patients (OR = 2.43, 95% CI: 1.26-4.68), comorbidity (OR = 2.08, 95% CI: 1.29-3.35), dyspnea (OR = 2.02, 95% CI: 1.34-3.04) associated with a higher risk of post-COVID-19 syndrome.

CONCLUSIONS: Our study showed that females, the severity of COVID-19, comorbidity, and dyspnea were associated with a higher risk of post-COVID-19 syndrome. More attention should be paid to these factors to prevent and treat post-COVID-19 syndrome.},
}

Female
Humans
Male
Comorbidity
*COVID-19/complications/diagnosis/epidemiology/virology
Dyspnea/diagnosis/epidemiology/virology
*Post-Acute COVID-19 Syndrome/diagnosis/epidemiology/virology
Prognosis
Risk Factors
SARS-CoV-2
Severity of Illness Index
Sex Factors

@article {pmid40304923,
year = {2025},
author = {Millhouse, PW and Bloom, RW and Beckstrand, JN and McClure, ML and Eckmann, MS and Feeko, KJ and Mojica, JJ},
title = {The Ganglia of the Head and Neck: Clinical Relevance for the Interventional Pain Physician.},
journal = {Current pain and headache reports},
volume = {29},
number = {1},
pages = {80},
pmid = {40304923},
issn = {1534-3081},
mesh = {Humans ; *Facial Pain/therapy/physiopathology ; *Pain Management/methods ; Nerve Block/methods ; *Headache/therapy ; *Headache Disorders/therapy ; Clinical Relevance ; },
abstract = {PURPOSE OF REVIEW: The purpose of this article is to provide a comprehensive review of the ganglia of the head and neck and their role in the interventional management of chronic headaches and facial pain disorders.

RECENT FINDINGS: Interventions targeting the sphenopalatine, stellate and gasserian ganglia are well described in the literature for headaches and facial pain disorders. There is a growing body of evidence supporting use of these techniques for clinical conditions outside of pain such as post-traumatic stress disorder and Long COVID symptoms. These findings increase the potential applications of such procedures, making them more relevant to the interventional physician tasked with managing symptoms in difficult to treat medical conditions. Nerve blocks of the head and neck are used for diagnostic and therapeutic purposes in the management of headaches and facial pain disorders. Headaches, whether acute or chronic, are common pain conditions with a wide-range of etiologies and are often difficult to treat. Chronic facial pain can have a variety of underlying causes, including direct or indirect nerve damage, infection, inflammation, and muscle dysfunction. Traditional pain management strategies such as medications and physical therapy often fail or are associated with significant adverse effects. Interventions such as nerve blocks and neuroablative procedures have shown promise in managing headaches and facial pain by directly targeting the underlying causes. This review article summarizes the most recent evidence regarding the efficacy, safety, applications and limitations of these interventional pain management techniques.},
}

Humans
*Facial Pain/therapy/physiopathology
*Pain Management/methods
Nerve Block/methods
*Headache/therapy
*Headache Disorders/therapy
Clinical Relevance

@article {pmid40284540,
year = {2025},
author = {Jason, LA and Katz, BZ},
title = {Predisposing and Precipitating Factors in Epstein-Barr Virus-Caused Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.},
journal = {Microorganisms},
volume = {13},
number = {4},
pages = {},
pmid = {40284540},
issn = {2076-2607},
abstract = {Long COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are two examples of post-viral syndromes. The identification of risk factors predisposing patients to developing and maintaining post-infectious syndromes may help uncover their underlying mechanisms. The majority of patients with ME/CFS report infectious illnesses before the onset of ME/CFS, with 30% of cases of ME/CFS due to IM caused by the Epstein-Barr virus. After developing IM, one study found 11% of adults had ME/CFS at 6 months and 9% had ME/CFS at 1 year. Another study of adolescents found 13% and 7% with ME/CFS at 6 and 12 months following IM, respectively. However, it is unclear which variables are potential risk factors contributing to the development and maintenance of ME/CFS following IM, because few prospective studies have collected baseline data before the onset of the triggering illness. The current article provides an overview of a study that included pre-illness predictors of ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. Our data set included an ethnically and sociodemographically diverse group of young adult students, and we were able to longitudinally follow these youths over time to better understand the risk factors associated with the pathophysiology of ME/CFS. General screens of health and psychological well-being, as well as blood samples, were obtained at three stages of the study (Stage 1-Baseline-when the students were well, at least 6 weeks before the student developed IM; Stage 2-within 6 weeks following the diagnosis of IM, and Stage 3-six months after IM, when they had either developed ME/CFS or recovered). We focused on the risk factors for new cases of ME/CFS following IM and found factors both at baseline (Stage 1) and at the time of IM (Stage 2) that predicted nonrecovery. We are now collecting seven-year follow-up data on this sample, as well as including cases of long COVID. The lessons learned in this prospective study are reviewed.},
}

@article {pmid40283075,
year = {2025},
author = {Loboda, D and Golba, KS and Gurowiec, P and Bredelytė, A and Razbadauskas, A and Sarecka-Hujar, B},
title = {Variability in Arterial Stiffness and Vascular Endothelial Function After COVID-19 During 1.5 Years of Follow-Up-Systematic Review and Meta-Analysis.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
pmid = {40283075},
issn = {2075-1729},
support = {BNW-2-016/N/4/K//Medical University of Silesia/ ; },
abstract = {Increasing long-term observations suggest that coronavirus disease 2019 (COVID-19) vasculopathy may persist even 1.5 years after the acute phase, potentially accelerating the development of atherosclerotic cardiovascular diseases. This study systematically reviewed the variability of brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (cfPWV) from the acute phase of COVID-19 through 16 months of follow-up (F/U). Databases including PubMed, Web of Science, MEDLINE, and Embase were screened for a meta-analysis without language or date restrictions (PROSPERO reference CRD42025642888, last search conducted on 1 February 2025). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Scale. We considered all studies (interventional pre-post studies, prospective observational studies, prospective randomized, and non-randomized trials) that assessed FMD or cfPWV in adults (aged ≥ 18 years) with or after laboratory-confirmed COVID-19 compared with non-COVID-19 controls or that assessed changes in these parameters during the F/U. Twenty-one studies reported differences in FMD, and 18 studies examined cfPWV between COVID-19 patients and control groups during various stages: acute/subacute COVID-19 (≤30 days from disease onset), early (>30-90 days), mid-term (>90-180 days), late (>180-270 days), and very late (>270 days) post-COVID-19 recovery. Six studies assessed variability in FMD, while nine did so for cfPWV during the F/U. Data from 14 FMD studies (627 cases and 694 controls) and 15 cfPWV studies (578 cases and 703 controls) were included in our meta-analysis. FMD showed a significant decrease compared to controls during the acute/subacute phase (standardized mean difference [SMD]= -2.02, p < 0.001), with partial improvements noted from the acute/subacute phase to early recovery (SMD = 0.95, p < 0.001) and from early to mid-term recovery (SMD = 0.92, p = 0.006). Normalization compared to controls was observed in late recovery (SMD = 0.12, p = 0.69). In contrast, cfPWV values, which were higher than controls in the acute/subacute phase (SMD = 1.27, p < 0.001), remained elevated throughout the F/U, with no significant changes except for a decrease from mid-term to very late recovery (SMD= -0.39, p < 0.001). In the very late recovery, cfPWV values remained higher than those of controls (SMD = 0.45, p = 0.010). In the manuscript, we discuss how various factors, including the severity of acute COVID-19, the persistence of long-term COVID-19 syndrome, and the patient's initial vascular age, depending on metrics age and cardiovascular risk factors, influenced the time and degree of FMD and cfPWV improvement.},
}

@article {pmid40278579,
year = {2025},
author = {Lan, L and Wang, Y and Chen, Y and Wang, T and Zhang, J and Tan, B},
title = {A Review on the Prevalence and Treatment of Antibiotic Resistance Genes in Hospital Wastewater.},
journal = {Toxics},
volume = {13},
number = {4},
pages = {},
pmid = {40278579},
issn = {2305-6304},
abstract = {Antibiotic resistance is a global environmental and health threat. Approximately 4.95 million deaths were associated with antibiotic resistance in 2019, including 1.27 million deaths that were directly attributable to bacterial antimicrobial resistance. Hospital wastewater is one of the key sources for the spread of clinically relevant antibiotic resistance genes (ARGs) into the environment. Understanding the current situation of ARGs in hospital wastewater is of great significance. Here, we review the prevalence of ARGs and antibiotic-resistant bacteria (ARB) in hospital wastewater and wastewater from other places and the treatment methods used. We further discuss the intersection between ARGs and COVID-19 during the pandemic. This review highlights the issues associated with the dissemination of critical ARGs from hospital wastewater into the environment. It is imperative to implement more effective processes for hospital wastewater treatment to eliminate ARGs, particularly during the current long COVID-19 period.},
}

@article {pmid40259865,
year = {2025},
author = {Bjorvatn, B and Merikanto, I and Chung, F and Holzinger, B and Morin, CM and Penzel, T and De Gennaro, L and Dauvilliers, Y and Wing, YK and Benedict, C and Xue, P and Reis, C and Korman, M and Landtblom, AM and Matsui, K and Hrubos-Strøm, H and Mota-Rolim, S and Nadorff, MR and Berezin, L and Sarkanen, T and Liu, Y and Scarpelli, S and Brandao, LEM and Cedernaes, J and Fränkl, EC and Partinen, E and Bolstad, CJ and Plazzi, G and Partinen, M and Espie, CA},
title = {Sleep During Pandemic Times: Summary of Findings and Future Outlook Through the Lens of the International COVID Sleep Study (ICOSS).},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e70076},
doi = {10.1111/jsr.70076},
pmid = {40259865},
issn = {1365-2869},
abstract = {To study the impact of the COVID-19 pandemic on sleep and circadian rhythms-two fundamental pillars for health-the collaboration International COVID-19 Sleep Study (ICOSS) was established. The present overview comprehensively discusses the findings from this collaboration. Involving sleep researchers across the globe, ICOSS used a harmonised questionnaire to cover changes in sleep and sleep disorders, as well as physical and mental health. Two survey waves were conducted, one in 2020 and another one in 2021. In ICOSS-1, a total of 26,539 people from 14 countries across four continents (Europe, Asia, North and South America) participated. In ICOSS-2, two more countries joined ICOSS, and 15,813 people participated. The focus in ICOSS-2 was on Long COVID. Participants accessed the widely disseminated online surveys in their native language. In the 20 papers published so far, the surveys have uncovered several novel findings, including how the pandemic impacted sleep patterns, the prevalence of sleep disorders, chronotype-based differences and sleep-immune system interactions. To the best of our knowledge, there is no other large-scale multinational study targeting the general population investigating the role of sleep and sleep disorders alongside a variety of psychological, biological, social and economic factors during the recent COVID-19 pandemic.},
}

@article {pmid40259563,
year = {2025},
author = {Cornish, F and Sabaine, B and Soares, L and Caldas, B and Portela, MC and Bousquat, A and Aveling, EL},
title = {The erasure of infection-associated chronic conditions: Critical interpretive synthesis of literature on healthcare for long COVID and related conditions in Brazil.},
journal = {Global public health},
volume = {20},
number = {1},
pages = {2490720},
doi = {10.1080/17441692.2025.2490720},
pmid = {40259563},
issn = {1744-1706},
mesh = {Humans ; Brazil/epidemiology ; *COVID-19/epidemiology/therapy/complications ; Chronic Disease/epidemiology/therapy ; SARS-CoV-2 ; *Delivery of Health Care ; Post-Acute COVID-19 Syndrome ; },
abstract = {Evidence is emerging that long COVID is at least as prevalent in the Global South as the Global North, but literature on long COVID healthcare in the Global South is in its infancy. Brazil is seeing significant levels of debility due to long COVID but a limited national evidence-base. long COVID shares symptomatology and appropriate care with a wider category of infection-associated chronic conditions (IACCs). This article reviews literature published between 2000 and 2023 addressing healthcare for long COVID and IACCs in Brazil, in the interest of exploring challenges and opportunities for the SUS (Brazil's universal health system) to offer appropriate long COVID healthcare. We find that long COVID and IACCs collectively are subject to erasure from Brazilian healthcare knowledge, through lack of expertise, a resource-limited health system prioritising urgent care, and the concentration of poor health in marginalised populations with limited decision-making power. A nascent intellectual will to address long COVID, and a tradition of social participation in healthcare governance present potential opportunities. We call for ignition of a global step-change in tackling healthcare for long COVID and IACCs. Global equity in long COVID healthcare requires the development and sharing of expertise regarding its universal and context-specific features.},
}

Humans
Brazil/epidemiology
*COVID-19/epidemiology/therapy/complications
Chronic Disease/epidemiology/therapy
SARS-CoV-2
*Delivery of Health Care
Post-Acute COVID-19 Syndrome

@article {pmid40246350,
year = {2025},
author = {Rubio-Casillas, A and Rodríguez-Quintero, CM and Hromić-Jahjefendić, A and Uversky, VN and Redwan, EM and Brogna, C},
title = {The essential role of prebiotics in restoring gut health in long COVID.},
journal = {Progress in molecular biology and translational science},
volume = {213},
number = {},
pages = {385-411},
doi = {10.1016/bs.pmbts.2025.01.004},
pmid = {40246350},
issn = {1878-0814},
mesh = {Humans ; *Prebiotics/administration & dosage ; *COVID-19/microbiology/immunology ; *Gastrointestinal Microbiome/drug effects ; SARS-CoV-2 ; Dysbiosis/microbiology ; Probiotics ; Pandemics ; },
abstract = {The gut microbiota (GM) plays an essential role in human health, influencing not only digestive processes but also the immune system´s functionality. The COVID-19 pandemic has highlighted the complex interaction between viral infections and the GM. Emerging evidence has demonstrated that SARS-CoV-2 can disrupt microbial homeostasis, leading to dysbiosis and compromised immune responses. The severity of COVID-19 has been associated with a reduction in the abundance of several beneficial bacteria in the gut. It has been proposed that consuming probiotics may help to re-colonize the GM. Although probiotics are important, prebiotics are essential for their metabolism, growth, and re-colonization capabilities. This chapter delves into the critical role of prebiotics in restoring GM after COVID-19 disease. The mechanisms by which prebiotics enhance the metabolism of beneficial bacteria will be described, and how prebiotics mediate the re-colonization of the gut with beneficial bacteria, thereby restoring microbial diversity and promoting the resilience of the gut-associated immune system. The benefits of consuming prebiotics from natural sources are superior to those from chemically purified commercial products.},
}

Humans
*Prebiotics/administration & dosage
*COVID-19/microbiology/immunology
*Gastrointestinal Microbiome/drug effects
SARS-CoV-2
Dysbiosis/microbiology
Probiotics
Pandemics

@article {pmid40246346,
year = {2025},
author = {Adilović, M},
title = {COVID-19 related complications.},
journal = {Progress in molecular biology and translational science},
volume = {213},
number = {},
pages = {259-314},
doi = {10.1016/bs.pmbts.2025.02.002},
pmid = {40246346},
issn = {1878-0814},
mesh = {Humans ; *COVID-19/complications ; *SARS-CoV-2 ; Pregnancy ; Pandemics ; Female ; },
abstract = {The COVID-19 pandemic has significantly impacted global healthcare systems, revealed vulnerabilities and prompted a re-evaluation of medical practices. Acute complications from the virus, including cardiovascular and neurological issues, have underscored the necessity for timely medical interventions. Advances in diagnostic methods and personalized therapies have been pivotal in mitigating severe outcomes. Additionally, Long COVID has emerged as a complex challenge, affecting various body systems and leading to respiratory, cardiovascular, neurological, psychological, and musculoskeletal problems. This broad spectrum of complications highlights the importance of multidisciplinary management approaches that prioritize therapy, rehabilitation, and patient-centered care. Vulnerable populations such as paediatric patients, pregnant women, and immunocompromised individuals face unique risks and complications, necessitating continuous monitoring and tailored management strategies to reduce morbidity and mortality associated with COVID-19.},
}

Humans
*COVID-19/complications
*SARS-CoV-2
Pregnancy
Pandemics
Female

@article {pmid40241147,
year = {2025},
author = {Morello, R and De Rose, C and Martino, L and Raffaelli, F and Zampino, G and Valentini, P and Buonsenso, D},
title = {Role of nutrient supplements in children with post-COVID condition: a retrospective preliminary observation and narrative review.},
journal = {Italian journal of pediatrics},
volume = {51},
number = {1},
pages = {119},
pmid = {40241147},
issn = {1824-7288},
mesh = {Humans ; *Dietary Supplements ; Retrospective Studies ; *COVID-19/complications ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Post-COVID Condition (PCC), emerging as a significant long-term consequence of SARS-CoV-2 infection, affects not only adults but also the pediatric population. Despite ongoing research, the precise pathophysiology of PCC remains elusive. However, several putative mechanisms have been identified, leading to the exploration of various therapeutic strategies. Notably, in the adult population, there has been substantial interest in the potential efficacy of nutritional supplements. Regrettably, information regarding the use of such supplements in the pediatric population is currently lacking.

METHODS: The present study was conducted to assess the impact of nutritional supplements on alleviating long COVID symptoms in children. To achieve this, we conducted a retrospective analysis of nutrient supplements administered by parents to children with Post-COVID Condition (PCC) between February 2020 and October 2022. Statistical analyses were employed to determine associations between categorical variables.

RESULTS: A total of 1243 children were enrolled following documented SARS-CoV-2 infection, with 940 (76.2%) diagnosed as recovered and 294 (23.8%) diagnosed with Long COVID. Among Long COVID patients experiencing disabling symptoms, treatment with oral lactoferrin and/or a Multi-Element Product (MEP) with antioxidant and anti-inflammatory properties was initiated. The correlation analysis between the use of supplements and persistence of long COVID at the next follow-up showed that the use of MEP alone (OR 5.7, 95% CI 3.8-8.5), or the combination of MEP and lactoferrin (OR 5.06, 95% CI 3.3-7.6) three months after the initial infection and for the following three months, were associated with a lower risk having long covid at six months following initial infection, when compared with the use of lactoferrin alone (OR 7.6 95% CI 5.1-11.4).

CONCLUSIONS: This proof-of-concept study revealed that MEP and lactoferrin, when administered three months after initial infection in patients with a new diagnosis of long covid, may have a positive impact on improving Long COVID symptoms in children during follow-up evaluations. This positive trend toward reducing Post-COVID Condition (PCC) exhibited by MEP and lactoferrin suggested a potential benefit worthy of exploration in future randomized controlled trials.},
}

Humans
*Dietary Supplements
Retrospective Studies
*COVID-19/complications
Child
Male
Female
Child, Preschool
Adolescent
SARS-CoV-2

@article {pmid40231214,
year = {2025},
author = {Serafini, RA and Frere, JJ and Giosan, IM and Nwaneshiudu, CA},
title = {SARS-CoV-2-induced sensory perturbations: A narrative review of clinical phenotypes, molecular pathologies, and possible interventions.},
journal = {Brain, behavior, & immunity - health},
volume = {45},
number = {},
pages = {100983},
pmid = {40231214},
issn = {2666-3546},
abstract = {BACKGROUND: The acute and post-acute sequelae of SARS-CoV-2 infection have been of great clinical interest since the inception of the COVID-19 pandemic. Despite a high prevalence of individuals with persistent symptoms, a wholistic view of the effects of SARS-CoV-2 on special sensory systems is lacking. Considering the significant impact of normal sensory function on quality of life, the goal of this review is to highlight unresolved issues related to SARS-CoV-2-associated insults to the sensory nervous system.

MAJOR FINDINGS: In this narrative review, we discuss the epidemiology of SARS-CoV-2-induced sensory perturbations, underlying pathological mechanisms, and possible therapeutic strategies across the olfactory, gustatory, somatosensory, visual, and auditory systems. Examined literature included studies with human biospecimens, human-derived cell lines, and naturally susceptible animal models, which highlighted evidence of persistent functional disruption in all sensory systems. SARS-CoV-2 infection was associated with persistent inflammation in the olfactory epithelium/bulb, somatosensory ganglia, and gustatory systems, long-term transcriptional perturbations in the sensory central nervous system and peripheral nervous system, and detectable degeneration/apoptosis in the gustatory and visual systems. Few studies have proposed evidence-based therapeutic strategies for attenuating specific sensory abnormalities after SARS-CoV-2 infection.

CONCLUSION: While the olfactory system, and to some extent the visual and somatosensory systems, have been more thoroughly investigated from symptomatology, behavioral and molecular perspectives, there is still an unmet need for the development of therapeutics to treat COVID-induced impairment of these systems. Further, additional attention must be placed on COVID-associated impairment of the gustatory, visual, and auditory systems, which lack detailed mechanistic investigations into their pathogenesis.},
}

@article {pmid40219044,
year = {2025},
author = {Marchesi, N and Allegri, M and Bruno, GM and Pascale, A and Govoni, S},
title = {Exploring the Potential of Dietary Supplements to Alleviate Pain Due to Long COVID.},
journal = {Nutrients},
volume = {17},
number = {7},
pages = {},
pmid = {40219044},
issn = {2072-6643},
mesh = {Humans ; *Dietary Supplements ; *COVID-19/complications ; SARS-CoV-2 ; *Chronic Pain/etiology ; Analgesics/therapeutic use ; *Pain Management/methods ; Post-Acute COVID-19 Syndrome ; *Pain/etiology/drug therapy ; },
abstract = {Long COVID, characterized by persistent symptoms following COVID-19 infection, significantly impacts individuals' health and daily functioning due to fatigue and pain. Focusing on pain, this review addresses nociplastic and chronic pain conditions. Interventions designed to reduce inflammation, oxidative stress, and enhance vagal activity may offer a promising approach to managing post-pandemic pain. This review presents individual components of food supplements with demonstrated efficacy in one or more pain conditions, focusing on their proposed mechanisms and clinical activity in pain, including their use in post-COVID-19 pain when available. Many of these substances have a long history of safe use and may offer an alternative to long-term analgesic drug treatment, which is often associated with potential side effects. This review also explores the potential for synergistic effects when combining these substances with each other or with conventional analgesics, considering the advantages for both patients and the healthcare system in using these substances as adjunctive or primary therapies for pain symptoms related to long COVID. While preclinical scientific literature provides a mechanistic basis for the action of several food supplements on pain control mechanisms and signaling pathways, clinical experience, particularly in the field of long COVID-associated pain, is still limited. However, the reviewed literature strongly suggests that the use of food supplements in long COVID-associated pain is an attainable goal, provided that rigorous clinical trials are conducted.},
}

Humans
*Dietary Supplements
*COVID-19/complications
SARS-CoV-2
*Chronic Pain/etiology
Analgesics/therapeutic use
*Pain Management/methods
Post-Acute COVID-19 Syndrome
*Pain/etiology/drug therapy

@article {pmid40212158,
year = {2025},
author = {Abbas, AH and Haji, MR and Shimal, AA and Kurmasha, YH and Al-Janabi, AAH and Azeez, ZT and Al-Ali, ARS and Al-Najati, HMH and Al-Waeli, ARA and Abdulhadi, NASA and Al-Tuaama, AZH and Al-Ashtary, MM and Hussin, OA},
title = {A multidisciplinary review of long COVID to address the challenges in diagnosis and updated management guidelines.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {4},
pages = {2105-2117},
pmid = {40212158},
issn = {2049-0801},
abstract = {Long COVID has emerged as a significant challenge since the COVID-19 pandemic, which was declared as an outbreak in March 2020, marked by diverse symptoms and prolonged duration of disease. Defined by the WHO as symptoms persisting or emerging for at least two months post-SARS-CoV-2 infection without an alternative cause, its prevalence varies globally, with estimates of 10-20% in Europe, 7.3% in the USA, and 3.0% in the UK. The condition's etiology remains unclear, involving factors, such as renin-angiotensin system overactivation, persistent viral reservoirs, immune dysregulation, and autoantibodies. Reactivated viruses, like EBV and HSV-6, alongside epigenetic alterations, exacerbate mitochondrial dysfunction and energy imbalance. Emerging evidence links SARS-CoV-2 to chromatin and gut microbiome changes, further influencing long-term health impacts. Diagnosis of long COVID requires detailed systemic evaluation through medical history and physical examination. Management is highly individualized, focusing mainly on the patient's symptoms and affected systems. A multidisciplinary approach is essential, integrating diverse perspectives to address systemic manifestations, underlying mechanisms, and therapeutic strategies. Enhanced understanding of long COVID's pathophysiology and clinical features is critical to improving patient outcomes and quality of life. With a growing number of cases expected globally, advancing research and disseminating knowledge on long COVID remain vital for developing effective diagnostic and management frameworks, ultimately supporting better care for affected individuals.},
}

@article {pmid40211768,
year = {2025},
author = {Gao, J and Zhao, D and Nouri, HR and Chu, HW and Huang, H},
title = {Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation.},
journal = {Immunological reviews},
volume = {331},
number = {1},
pages = {e70026},
pmid = {40211768},
issn = {1600-065X},
support = {R01 AI083986/AI/NIAID NIH HHS/United States ; R01AI152504/NH/NIH HHS/United States ; U19 AI125357/AI/NIAID NIH HHS/United States ; R01AI107022/NH/NIH HHS/United States ; R01 AI107022/AI/NIAID NIH HHS/United States ; R01 AI150082/AI/NIAID NIH HHS/United States ; R01AI150082/NH/NIH HHS/United States ; R01 AI152504/AI/NIAID NIH HHS/United States ; R56 AI180204/AI/NIAID NIH HHS/United States ; R01 AI161296/AI/NIAID NIH HHS/United States ; R01AI161296/NH/NIH HHS/United States ; R01AI083986/NH/NIH HHS/United States ; R01 AI182277/AI/NIAID NIH HHS/United States ; U19AI125357/NH/NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Mast Cells/immunology/metabolism ; Cell Differentiation/genetics ; Mice ; *Lung/immunology ; Gene Expression Regulation ; Inflammation/immunology ; *COVID-19/immunology ; Transcription Factors/metabolism ; *SARS-CoV-2/immunology ; },
abstract = {Mast cells (MCs) play a critical role in allergic inflammation, anaphylaxis, and chronic inflammatory diseases such as asthma, COPD, and osteoarthritis. Dysregulated MC activation can lead to MC activation syndrome (MACS), which is observed in patients with long COVID. MCs express the high-affinity receptor for IgE and, upon activation, release mediators and cytokines that trigger anaphylactic shock and promote allergic inflammation. They also interact with epithelial and nerve cells, which are crucial in forming a complex network of cell-cell and gene-gene interactions driving chronic inflammation that can confer resistance to treatment. In this review, in the context of the literature, we focus on experiments conducted in our laboratory investigating how transcription factors and enhancers regulate genes critical in mouse MC differentiation and function related to human lung inflammation.},
}

Animals
Humans
*Mast Cells/immunology/metabolism
Cell Differentiation/genetics
Mice
*Lung/immunology
Gene Expression Regulation
Inflammation/immunology
*COVID-19/immunology
Transcription Factors/metabolism
*SARS-CoV-2/immunology

@article {pmid40210368,
year = {2025},
author = {Verduzco-Gutierrez, M and Fleming, TK and Azola, AM},
title = {Considerations for Long COVID Rehabilitation in Women.},
journal = {Physical medicine and rehabilitation clinics of North America},
volume = {36},
number = {2},
pages = {371-387},
doi = {10.1016/j.pmr.2024.11.009},
pmid = {40210368},
issn = {1558-1381},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; Female ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Sex Factors ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic has given rise to long COVID, a prolonged manifestation of severe acute respiratory syndrome coronavirus 2 infection, which presents with varied symptoms and conditions lasting beyond expected acute illness. Despite efforts, diagnostic and treatment approaches remain insufficient, particularly for women who experience higher prevalence rates. Rehabilitation professionals have played a crucial role during the pandemic. Individualized rehabilitation plans, encompassing various therapies and interdisciplinary collaborations, are essential. Addressing disparities and biological sex differences is paramount, requiring increased research, understanding, and advocacy for effective rehabilitative care tailored to all individuals affected by long COVID.},
}

Humans
*COVID-19/rehabilitation/epidemiology
Female
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Sex Factors

@article {pmid40199308,
year = {2024},
author = {Bona, JP},
title = {Knowledge Representation and Management in the Age of Long Covid and Large Language Models: a 2022-2023 Survey.},
journal = {Yearbook of medical informatics},
volume = {33},
number = {1},
pages = {216-222},
pmid = {40199308},
issn = {2364-0502},
mesh = {Humans ; *Artificial Intelligence ; COVID-19 ; *Large Language Models ; Surveys and Questionnaires ; *Post-Acute COVID-19 Syndrome/epidemiology ; },
abstract = {OBJECTIVES: To select, present, and summarize cutting edge work in the field of Knowledge Representation and Management (KRM) published in 2022 and 2023.

METHODS: A comprehensive set of KRM-relevant articles published in 2022 and 2023 was retrieved by querying PubMed. Topic modeling with Latent Dirichlet Allocation was used to further refine this query and suggest areas of focus. Selected articles were chosen based on a review of their title and abstract.

RESULTS: An initial set of 8,706 publications were retrieved from PubMed. From these, fifteen papers were ultimately selected matching one of two main themes: KRM for long COVID, and KRM approaches used in combination with generative large language models.

CONCLUSIONS: This survey shows the ongoing development and versatility of KRM approaches, both to improve our understanding of a global health crisis and to augment and evaluate cutting edge technologies from other areas of artificial intelligence.},
}

Humans
*Artificial Intelligence
COVID-19
*Large Language Models
Surveys and Questionnaires
*Post-Acute COVID-19 Syndrome/epidemiology

@article {pmid40195851,
year = {2025},
author = {Chung, J and Pierce, J and Franklin, C and Olson, RM and Morrison, AR and Amos-Landgraf, J},
title = {Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.},
journal = {Disease models & mechanisms},
volume = {18},
number = {9},
pages = {},
pmid = {40195851},
issn = {1754-8411},
support = {IK2BX002527//U.S. Department of Veterans Affairs/ ; I01 CX002231/CX/CSRD VA/United States ; R01 HL163005/HL/NHLBI NIH HHS/United States ; T32 OD011126/OD/NIH HHS/United States ; P20 GM103652/GM/NIGMS NIH HHS/United States ; T32OD011126//NIH Office of the Director/ ; R01 HL139795/HL/NHLBI NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; IK2 BX002527/BX/BLRD VA/United States ; U42OD010918//Institutes of Health (NIH)/ ; },
mesh = {*COVID-19/complications/pathology/virology ; Animals ; *Disease Models, Animal ; *SARS-CoV-2/physiology ; *Gastrointestinal Diseases/virology/etiology/pathology ; Humans ; *Nervous System Diseases/virology/etiology/pathology ; *Vascular Diseases/virology/etiology ; Gastrointestinal Tract/pathology/virology ; *Translational Research, Biomedical ; },
abstract = {Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated a global pandemic resulting in an estimated 775 million infections with over 7 million deaths, it has become evident that COVID-19 is not solely a pulmonary disease. Emerging evidence has shown that, in a subset of patients, certain symptoms - including chest pain, stroke, anosmia, dysgeusia, diarrhea and abdominal pain - all indicate a role of vascular, neurological and gastrointestinal (GI) pathology in the disease process. Many of these disease processes persist long after the acute disease has been resolved, resulting in 'long COVID' or post-acute sequelae of COVID-19 (PASC). The molecular mechanisms underlying the acute and systemic conditions associated with COVID-19 remain incompletely defined. Appropriate animal models provide a method of understanding underlying disease mechanisms at the system level through the study of disease progression, tissue pathology, immune system response to the pathogen and behavioral responses. However, very few studies have addressed PASC and whether existing models hold promise for studying this challenging problem. Here, we review the current literature on cardiovascular, neurological and GI pathobiology caused by COVID-19 in patients, along with established animal models of the acute disease manifestations and their prospects for use in PASC studies. Our aim is to provide guidance for the selection of appropriate models in order to recapitulate certain aspects of the disease to enhance the translatability of mechanistic studies.},
}

*COVID-19/complications/pathology/virology
Animals
*Disease Models, Animal
*SARS-CoV-2/physiology
*Gastrointestinal Diseases/virology/etiology/pathology
Humans
*Nervous System Diseases/virology/etiology/pathology
*Vascular Diseases/virology/etiology
Gastrointestinal Tract/pathology/virology
*Translational Research, Biomedical

@article {pmid40193038,
year = {2025},
author = {Sadowski, J and Ostrowska, SA and Klaudel, T and Zaborska, M and Chruszcz, M and Sztangreciak-Lehun, A and Bułdak, RJ},
title = {Neuropsychiatric disorders in the course to SARS-CoV-2 virus infection, including biological pathomechanisms, psychosocial factors and long COVID-19 associated with "brain fog".},
journal = {Journal of neurovirology},
volume = {},
number = {},
pages = {},
pmid = {40193038},
issn = {1538-2443},
abstract = {During the COVID-19 pandemic, neuropsychiatric disorders began to be observed in a significant proportion of patients, occurring at different times after infection and characterised by varying degrees of severity. This article discusses neurological and psychiatric disorders associated with SARS-CoV-2 virus infection, taking into account biological pathomechanisms and psychosocial factors. The long COVID-19 along with the "brain fog" phenomenon were considered in the study. The purpose of the study is to analyse and discuss the available information from the scientific literature on the possible association between SARS-CoV-2 virus infection and the occurrence of neuropsychiatric disorders with different degrees of severity and temporal correlation. To discuss the correlation of COVID-19 with the occurrence of neuropsychiatric disorders, a systematic literature review was conducted using the following databases: PubMed, Elsevier and Google Scholar. The following keywords were used when searching the materials used: "neuropsychiatric disorders", "COVID-19", "SARS-CoV-2", "NeuroCOVID", "cytokine storm" and "long COVID-19". Focusing on the characteristics of the materials and methods used, as well as the results obtained and conclusions reached in each article, 164 publications of research, meta-analysis, review and case reports were included in the study. Neuropsychiatric disorders resulting from SARS-CoV-2 virus infection are multifactorial in nature. The main elements responsible for the varied pattern of symptoms include direct and indirect central nervous system effects of the disease, individual patient conditions, psychosocial factors, severity of immune responses and severity of infection. The neuropsychiatric effects of SARS-CoV-2 infection can be divided into symptoms directly related to the neurological and psychiatric zones and mixed disorders.},
}

@article {pmid40180726,
year = {2025},
author = {Diener, HC},
title = {[Not Available].},
journal = {MMW Fortschritte der Medizin},
volume = {167},
number = {6},
pages = {30},
doi = {10.1007/s15006-025-4871-1},
pmid = {40180726},
issn = {1613-3560},
}

@article {pmid40175252,
year = {2025},
author = {Tarasco, MC and Iacomino, N and Mantegazza, R and Cavalcante, P},
title = {COVID-19, Epstein-Barr virus reactivation and autoimmunity: Casual or causal liaisons?.},
journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jmii.2025.03.014},
pmid = {40175252},
issn = {1995-9133},
abstract = {The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus infection, has been associated with a substantial risk of autoimmune disease development or exacerbation. The postulated pathophysiological mechanisms linking COVID-19 with autoimmunity include reactivation of latent Epstein-Barr virus (EBV), whose dysregulated infection in the host can trigger or promote an autoimmune response. This review summarizes recent studies highlighting a potential immunopathogenetic link between SARS-CoV-2 infection and EBV reactivation, which could underlie autoimmunity onset or worsening, as well as immune-related long COVID manifestations in COVID-19 patients. We offer our perspective on the direction that research should take to disentangle the nature (whether causal or casual) of the "COVID-19-EBV-autoimmunity" liaisons. Further advances in this research area may be crucial for designing strategies to prevent or treat EBV reactivation-related autoimmune conditions in COVID-19 patients, or patients with inflammatory co-infectious diseases, at the same time promising to improve our knowledge on the viral contribution to autoimmune phenomena.},
}

@article {pmid40170623,
year = {2025},
author = {Iqbal, MM and Iqbal, A and Evans, RA},
title = {Long COVID update: respiratory sequelae and symptoms.},
journal = {Current opinion in supportive and palliative care},
volume = {19},
number = {2},
pages = {95-102},
doi = {10.1097/SPC.0000000000000755},
pmid = {40170623},
issn = {1751-4266},
mesh = {Humans ; *COVID-19/complications/physiopathology/therapy ; *Dyspnea/etiology/virology ; Cough/etiology/virology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Lung Diseases, Interstitial/etiology/therapy/virology/physiopathology ; },
abstract = {PURPOSE OF REVIEW: Long COVID affects approximately 6% of the population after SARS-CoV-2 infection commonly involving persistent respiratory symptoms such as breathlessness and cough. This review provides an update on the latest evidence regarding post-COVID condition/Long COVID and respiratory sequelae, focusing on persistent symptoms, respiratory complications, and therapeutic approaches to date.

RECENT FINDINGS: Post-COVID interstitial lung abnormalities are estimated to persist in approximately 11% of patients hospitalized with acute COVID-19. However, breathlessness is common in adults (non-hospitalized) with Long COVID, suggesting aetiologies beyond pneumonitis. The risk of venous thromboembolic disease in Long COVID remains uncertain and trial results of anti-coagulation in Long COVID are awaited.

SUMMARY: Long COVID presents complex respiratory challenges, and careful assessment is crucial to differentiate Long COVID symptoms from exacerbations of pre-existing respiratory conditions. Current management includes a symptom-based multidisciplinary approach, with ongoing research into effective treatments including immune modulating agents.},
}

Humans
*COVID-19/complications/physiopathology/therapy
*Dyspnea/etiology/virology
Cough/etiology/virology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
*Lung Diseases, Interstitial/etiology/therapy/virology/physiopathology

@article {pmid40167111,
year = {2025},
author = {Ocampo, FF and Holroyd, KB},
title = {Updates on the neurological manifestations of SARS-CoV-2 infection.},
journal = {Current opinion in infectious diseases},
volume = {38},
number = {3},
pages = {234-241},
doi = {10.1097/QCO.0000000000001110},
pmid = {40167111},
issn = {1473-6527},
mesh = {Humans ; *COVID-19/complications ; *Nervous System Diseases/virology/etiology/therapy ; *SARS-CoV-2 ; },
abstract = {PURPOSE OF REVIEW: Since its emergence in 2020, the COVID-19 pandemic has created a global surge of survivors experiencing neurologic effects from SARS-CoV-2 infection. This review aims to provide an updated synthesis of the acute and chronic neurological manifestations of COVID-19, and to outline the current therapeutic strategies for these conditions.

RECENT FINDINGS: Epidemiological studies have shown that COVID-19 patients with neurological symptoms during acute infection tend to have poorer hospital and functional outcomes. While the risk of adverse neurologic symptoms including cognitive dysfunction, headache, autonomic dysfunction, and chronic fatigue are thought to be greatest following infection with the original SARS-CoV-2 strain and its alpha variant, they remain prevalent after infection with subsequent less virulent strains as well. Some recent work has also found a link between SARS-CoV-2 and structural brain changes. However, ongoing trials show promising results for pharmacologic and nonpharmacologic treatments targeting the postacute neurological sequelae of COVID-19.

SUMMARY: Lingering neurological manifestations after COVID-19 still pose considerable individual, healthcare system, and socioeconomic repercussions. Both preventive and multimodal treatment approaches are necessary to address these conditions. Further research is required to assess the lasting impacts of SARS-CoV-2 on the nervous system, particularly its potential contribution to the development of neurodegenerative diseases.},
}

Humans
*COVID-19/complications
*Nervous System Diseases/virology/etiology/therapy
*SARS-CoV-2

@article {pmid40159916,
year = {2025},
author = {Sterian, M and Naganathan, T and Corrin, T and Waddell, L},
title = {Evidence on the associations and safety of COVID-19 vaccination and post COVID-19 condition: an updated living systematic review.},
journal = {Epidemiology and infection},
volume = {153},
number = {},
pages = {e62},
pmid = {40159916},
issn = {1469-4409},
mesh = {Humans ; *COVID-19 Vaccines/adverse effects/administration & dosage ; *COVID-19/prevention & control/complications ; *Vaccination/adverse effects ; Child ; SARS-CoV-2 ; Adolescent ; },
abstract = {Post COVID-19 condition (PCC) refers to persistent symptoms occurring ≥12 weeks after COVID-19. This living systematic review (SR) assessed the impact of vaccination on PCC and vaccine safety among those with PCC, and was previously published with data up to December 2022. Searches were updated to 31 January 2024 and standard SR methodology was followed. Seventy-eight observational studies were included (47 new). There is moderate confidence that two doses pre-infection reduces the odds of PCC (pooled OR (pOR) 0.69, 95% CI 0.64-0.74, I[2] = 35.16%). There is low confidence for remaining outcomes of one dose and three or more doses. A booster dose may further reduce the odds of PCC compared to only a primary series (pOR 0.85, 95% CI 0.74-0.98, I[2] = 16.85%). Among children ≤18 years old, vaccination may not reduce the odds (pOR 0.79, 95% CI 0.56-1.11, I[2] = 37.2%) of PCC. One study suggests that vaccination within 12 weeks post-infection may reduce the odds of PCC. For those with PCC, vaccination appears safe (four studies) and may reduce the odds of PCC persistence (pOR 0.73, 95% CI 0.57-0.92, I[2] = 15.5%).},
}

Humans
*COVID-19 Vaccines/adverse effects/administration & dosage
*COVID-19/prevention & control/complications
*Vaccination/adverse effects
Child
SARS-CoV-2
Adolescent

@article {pmid40152069,
year = {2025},
author = {Chen, YH and Jan, JS and Yang, CH and Yen, TL and Linh, TTD and Annavajjula, S and Satapathy, MK and Tsao, SY and Hsieh, CY},
title = {Cognitive Sequelae of COVID-19: Mechanistic Insights and Therapeutic Approaches.},
journal = {CNS neuroscience & therapeutics},
volume = {31},
number = {3},
pages = {e70348},
pmid = {40152069},
issn = {1755-5949},
support = {R113-020//Ditmanson Medical Foundation Chia-Yi Christian Hospital/ ; CGH-A10610//Cathay General Hospital/ ; },
mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/etiology/therapy ; SARS-CoV-2 ; Animals ; Neuroinflammatory Diseases ; },
abstract = {BACKGROUND: The COVID-19 pandemic has left an indelible mark on the world, with mounting evidence suggesting that it not only posed acute challenges to global healthcare systems but has also unveiled a complex array of long-term consequences, particularly cognitive impairment (CI). As the persistence of post-COVID-19 neurological syndrome could evolve into the next public health crisis, it is imperative to gain a better understanding of the intricate pathophysiology of CI in COVID-19 patients and viable treatment strategies.

METHODS: This comprehensive review explores the pathophysiology and management of cognitive impairment across the phases of COVID-19, from acute infection to Long-COVID, by synthesizing findings from clinical, preclinical, and mechanistic studies to identify key contributors to CI, as well as current therapeutic approaches.

RESULTS: Key mechanisms contributing to CI include persistent neuroinflammation, cerebrovascular complications, direct neuronal injury, activation of the kynurenine pathway, and psychological distress. Both pharmacological interventions, such as anti-inflammatory therapies and agents targeting neuroinflammatory pathways, and non-pharmacological strategies, including cognitive rehabilitation, show promise in addressing these challenges. Although much of the current evidence is derived from preclinical and animal studies, these findings provide foundational insights into potential treatment approaches.

CONCLUSION: By synthesizing current knowledge, this review highlights the importance of addressing COVID-19-related cognitive impairment and offers actionable insights for mitigation and recovery as the global community continues to grapple with the pandemic's long-term impact.},
}

Humans
*COVID-19/complications/psychology
*Cognitive Dysfunction/etiology/therapy
SARS-CoV-2
Animals
Neuroinflammatory Diseases

@article {pmid40141784,
year = {2025},
author = {Caliman-Sturdza, OA and Gheorghita, R and Lobiuc, A},
title = {Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {3},
pages = {},
pmid = {40141784},
issn = {2075-1729},
abstract = {The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. One of the lesser-known but significant aspects of L-C19 is its impact on neuropsychiatric manifestations, which can have a profound effect on an individual's quality of life. Research shows that L-C19 creates neuropsychiatric issues such as mental fog, emotional problems, and brain disease symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors with seizures, and pain in nerves. People with cognitive problems plus fatigue and mood disorders experience great difficulty handling everyday activities, personal hygiene, and social interactions. Neuropsychiatric symptoms make people withdraw from social activity and hurt relationships, thus causing feelings of loneliness. The unpredictable state of L-C19 generates heavy psychological pressure through emotional suffering, including depression and anxiety. Neuropsychiatric changes such as cognitive impairment, fatigue, and mood swings make it hard for people to work or study effectively, which decreases their output at school or work and lowers their job contentment. The purpose of this narrative review is to summarize the clinical data present in the literature regarding the neuropsychiatric manifestations of L-C19, to identify current methods of diagnosis and treatment that lead to correct management of the condition, and to highlight the impact of these manifestations on patients' quality of life.},
}

@article {pmid40141748,
year = {2025},
author = {Stasi, C},
title = {Post-COVID-19 Pandemic Sequelae in Liver Diseases.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {3},
pages = {},
pmid = {40141748},
issn = {2075-1729},
abstract = {During the coronavirus disease 2019 (COVID-19) pandemic, several studies highlighted a worse prognosis for patients with alterations in liver function tests, especially those with pre-existing liver diseases. However, further studies are needed to define the long-term impact of the COVID-19 pandemic on liver diseases. Long COVID-19 encompasses a wide range of signs and symptoms, including exacerbations of pre-existing chronic conditions or new onset conditions developed after the COVID-19 acute phase. Therefore, the long-term effects of COVID-19 extensively include hepatic manifestations. The co-expression of angiotensin-converting receptor 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) has been demonstrated also in enterocytes, cholangiocytes, and hepatocytes. Studies on the post-COVID-19 sequelae have shown the presence of steatosis and necroinflammation in the liver, concomitantly with an alteration of inflammation, cytolysis and cholestasis indices. Some studies also demonstrated an increased risk for hepatobiliary pathologies, including secondary biliary cholangitis and worsening of the severity of metabolic-associated fatty liver disease (MASLD). Based on these premises, this review aims to provide an overview of the pathophysiological mechanisms contributing to COVID-19-related liver and hepatobiliary damage; explore its implications for liver inflammation and fibrosis, with a particular focus on MASLD and metabolic dysfunction-associated steatohepatitis (MASH); and analyze the short- and long-term COVID-19 sequelae. A literature search was conducted using the PubMed database for relevant studies published in English.},
}

@article {pmid40140333,
year = {2025},
author = {Wei, C and Jiang, W and Luo, M and Shao, F},
title = {BBB breakdown caused by plasma membrane pore formation.},
journal = {Trends in cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tcb.2025.02.012},
pmid = {40140333},
issn = {1879-3088},
abstract = {The blood-brain barrier, recently reintroduced as the blood-brain border (BBB), is a dynamic interface between the central nervous system (CNS) and the bloodstream. Disruption of the BBB exposes the CNS to peripheral pathogens and harmful substances, causing or worsening various CNS diseases. While traditional views attribute BBB failure to tight junction disruption or increased transcytosis, recent studies highlight the critical role of gasdermin D (GSDMD) pore formation in brain endothelial cells (bECs) during BBB disruption by lipopolysaccharide (LPS) or bacterial infections. This mechanism may also be involved in neurological complications like the 'brain fog' seen in long COVID. Pore formation in bECs may represent a prevalent mechanism causing BBB leakage. Investigating membrane-permeabilizing pores or channels and their effects on BBB integrity is a growing area of research. Further exploration of molecular processes that maintain, disrupt, and restore bEC membrane integrity will advance our understanding of brain vasculature and aid in developing new therapies for BBB-related diseases.},
}

@article {pmid40137051,
year = {2025},
author = {Kukreti, S and Lu, MT and Yeh, CY and Ko, NY},
title = {Physiological Sensors Equipped in Wearable Devices for Management of Long COVID Persisting Symptoms: Scoping Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e69506},
pmid = {40137051},
issn = {1438-8871},
mesh = {Humans ; *Wearable Electronic Devices ; *COVID-19/therapy/diagnosis ; Monitoring, Physiologic/instrumentation/methods ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Wearable technology has evolved in managing COVID-19, offering early monitoring of key physiological parameters. However, the role of wearables in tracking and managing long COVID is less understood and requires further exploration of their potential.

OBJECTIVE: This review assessed the application and effectiveness of wearable devices in managing long COVID symptoms, focusing on commonly used sensors and their potential for improving long-term patient care.

METHODS: A literature search was conducted across databases including PubMed, Embase, Web of Science, and Cochrane Central, adhering to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) reporting guidelines. The search was updated regularly throughout 2024. Abstract and full-text screening and selection were facilitated using Rayyan software developed by Qatar Computing Research Institute. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) critical appraisal tool to ensure the methodological rigor of the included studies. Data were extracted on study characteristics, wearable devices, sensors used, and monitored physiological parameters, and the results were synthesized in a narrative format.

RESULTS: A total of 1186 articles were identified, and after duplicate removal and screening, 15 studies were initially included, with 11 studies meeting the criteria for final data synthesis. The included studies varied in design, ranging from observational to interventional trials, and involved sample sizes from 3 to 17,667 participants across different countries. In total, 10 different wearable devices were used to monitor long COVID symptoms, capturing key metrics such as heart rate variability, body temperature, sleep, and physical activity. Smartwatches were the most used wearable devices and fitness trackers with electrocardiography and photoplethysmography sensors were used to monitor heart rate, oxygen saturation, and respiratory rate. Of the 10 devices, 4 were Food and Drug Administration-approved, emphasizing the reliability and validation of the physiological data collected. Studies were primarily conducted in the United States and Europe, reflecting significant regional research interest in wearable technology for long COVID management.

CONCLUSIONS: This review highlights the potential of wearable technology in providing continuous and personalized monitoring for long COVID patients. Although wearables show promise in tracking persistent symptoms, further research is needed to improve usability, validate long-term efficacy, and enhance patient engagement.},
}

Humans
*Wearable Electronic Devices
*COVID-19/therapy/diagnosis
Monitoring, Physiologic/instrumentation/methods
SARS-CoV-2

@article {pmid40126325,
year = {2025},
author = {Nyasulu, PS and Tamuzi, JL and Oliveira, RKF and Oliveira, SD and Petrosillo, N and de Jesus Perez, V and Dhillon, N and Butrous, G},
title = {COVID-19 and Parasitic Co-Infection: A Hypothetical Link to Pulmonary Vascular Disease.},
journal = {Infectious disease reports},
volume = {17},
number = {2},
pages = {},
pmid = {40126325},
issn = {2036-7430},
abstract = {Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern-both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections.},
}

@article {pmid40122540,
year = {2025},
author = {McDowell, CP and Tyner, B and Shrestha, S and McManus, L and Comaskey, F and Harrington, P and Walsh, KA and O'Neill, M and Ryan, M},
title = {Effectiveness and tolerance of exercise interventions for long COVID: a systematic review of randomised controlled trials.},
journal = {BMJ open},
volume = {15},
number = {3},
pages = {e082441},
pmid = {40122540},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/prevention & control/therapy ; *Randomized Controlled Trials as Topic ; *Exercise Therapy/methods ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Quality of Life ; Treatment Outcome ; },
abstract = {OBJECTIVES: To examine the effectiveness of exercise interventions to improve long COVID symptoms and the tolerance of exercise interventions among people with long COVID.

DESIGN: Systematic review.

DATA SOURCES: Medline via EBSCOhost, Embase via OVID and CENTRAL via the Cochrane Library up to 28 February 2023.

Inclusion criteria were: (1) participants with long COVID, as defined by study authors; (2) random assignment to either an exercise intervention or a comparison group and (3) a quantitative measure of at least 1 of the 12 core long COVID outcomes. Exclusion criteria were: (1) signs or symptoms not reasonably attributable to prior SARS-CoV-2 infection; (2) pre-exposure or postexposure prophylaxis for COVID-19 or the prevention of long COVID symptoms and (3) interventions where the primary exercise component is breathing or respiratory muscle training.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data, and studies were narratively synthesised.

RESULTS: Eight studies were included. Follow-up periods ranged from 2 to 28 weeks (mean=8.5 weeks). Sample sizes ranged from 39 to 119 (mean=56). All studies were in adults (mean age=49.9 years) and both sexes (mean female proportion=53.9%). Four studies were at low risk of bias, two were unclear and two were high. The evidence suggests that exercise interventions lead to short-term improvements in dyspnoea, fatigue, physical function and the physical domain of quality of life among people with long COVID. Of the five studies that reported adverse events, rates were low and, when reported, mild. Of the seven studies that reported sufficient relevant information, 1 of 252 participants who received exercise discontinued the intervention due to tolerance-related issues.

CONCLUSION: Available evidence suggests that exercise interventions may be beneficial and tolerable among some people with long COVID. However, the evidence base consists of a limited number of studies with small sample sizes and short follow-up periods.},
}

Humans
*COVID-19/prevention & control/therapy
*Randomized Controlled Trials as Topic
*Exercise Therapy/methods
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Quality of Life
Treatment Outcome

@article {pmid40120171,
year = {2025},
author = {Das Sarma, J},
title = {Murine β-coronavirus spike protein: A major determinant of neuropathogenic properties.},
journal = {Virology},
volume = {606},
number = {},
pages = {110499},
doi = {10.1016/j.virol.2025.110499},
pmid = {40120171},
issn = {1096-0341},
mesh = {Animals ; *Spike Glycoprotein, Coronavirus/metabolism/genetics ; *Murine hepatitis virus/physiology/genetics ; Mice ; Humans ; SARS-CoV-2/genetics/physiology ; COVID-19/virology ; Disease Models, Animal ; Coronavirus Infections/virology ; },
abstract = {Coronaviruses have emerged as a significant challenge to human health. While earlier outbreaks of coronaviruses such as SARS-CoV and MERS-CoV posed serious threats, the recent SARS-CoV-2 pandemic has heightened interest in coronavirus research due to its pulmonary pathology, in addition to its neurological manifestations. In addition, the patients who have recovered from SARS-CoV-2 infection show long-term symptoms such as anosmia, brain fog and long COVID. A major hurdle in studying these viruses is the limited availability of specialized research facilities, emphasizing the need for prototype virus-based models to investigate the pathophysiology. The mouse hepatitis virus (MHV), a member of the β-coronavirus family, serves as an excellent model to unravel the mechanisms underlying virus-induced pathogenesis. This review highlights two decades of research efforts aimed at understanding the pathophysiological mechanism of coronavirus-induced diseases, focusing on the development of targeted recombinant strains to identify the minimal essential motif of the spike protein responsible for fusogenicity and neuropathogenicity. By synthesizing findings from these studies, the review identifies the most promising therapeutic targets against coronaviruses, paving the way for the development of pan-coronavirus antivirals.},
}

Animals
*Spike Glycoprotein, Coronavirus/metabolism/genetics
*Murine hepatitis virus/physiology/genetics
Mice
Humans
SARS-CoV-2/genetics/physiology
COVID-19/virology
Disease Models, Animal
Coronavirus Infections/virology

@article {pmid40094929,
year = {2025},
author = {Patrascu, R and Dumitru, CS},
title = {Advances in Understanding Inflammation and Tissue Damage: Markers of Persistent Sequelae in COVID-19 Patients.},
journal = {Journal of clinical medicine},
volume = {14},
number = {5},
pages = {},
pmid = {40094929},
issn = {2077-0383},
abstract = {This review explores the crucial role of established and emerging biomarkers in the diagnosis, management, and understanding of post-COVID-19 conditions. With COVID-19 affecting multiple organ systems, biomarkers have been instrumental in identifying ongoing inflammation and tissue damage, facilitating early diagnosis and prognostication. Specifically, markers like C-reactive protein (CRP), interleukin-6 (IL-6), and novel entities such as soluble urokinase plasminogen activator receptor (suPAR) and neutrophil extracellular traps (NETs) provide insights into the pathophysiological mechanisms and predict long-term outcomes. This review highlights the integration of these biomarkers into clinical workflows and their implications for personalized medicine, emphasizing their potential in guiding therapeutic interventions and monitoring recovery. Future directions suggest a focus on longitudinal studies to explore biomarker trajectories and their interaction with therapeutic outcomes, aiming to enhance the management of post-COVID-19 conditions and refine public health strategies.},
}

@article {pmid40094893,
year = {2025},
author = {Mara, G and Nini, G and Cotoraci, C},
title = {Impact of Pulmonary Comorbidities on COVID-19: Acute and Long-Term Evaluations.},
journal = {Journal of clinical medicine},
volume = {14},
number = {5},
pages = {},
pmid = {40094893},
issn = {2077-0383},
abstract = {Background/Objectives: Pulmonary comorbidities, such as chronic obstructive pulmonary disease (COPD), asthma, and interstitial lung diseases (ILDs), have emerged as critical factors influencing the severity and outcomes of COVID-19. This review aims to evaluate the interplay between these comorbidities and COVID-19, both during the acute phase and in long-term recovery, focusing on their impact on clinical management and outcomes. Methods: This systematic review examined studies sourced from major medical databases, including PubMed and Scopus, using keywords such as "COVID-19", "pulmonary comorbidities", "long COVID", and "respiratory sequelae". Peer-reviewed articles published from January 2020 to the present were included, with data extracted to evaluate both the acute and long-term effects of these comorbidities on COVID-19 patients. Results: Patients with COPD demonstrated significantly higher risks of severe COVID-19, including increased hospitalization and mortality. Asthma, while less consistently associated with severe outcomes, showed a variable risk based on disease control. ILDs were strongly correlated with poor outcomes, including higher rates of respiratory failure and mortality. Long-term complications, such as persistent dyspnea, impaired lung function, and structural changes like fibrosis, were prevalent in patients recovering from moderate to severe COVID-19. These complications adversely affected quality of life and increased healthcare dependency. Conclusions: Pulmonary comorbidities amplify both the acute severity and long-term respiratory consequences of COVID-19. Effective management necessitates tailored strategies addressing both phases, integrating rehabilitation and continuous monitoring to mitigate chronic impairments. Future research should prioritize understanding the mechanisms behind these interactions to inform public health interventions and improve patient outcomes.},
}

@article {pmid40093756,
year = {2025},
author = {Sanger, BD and Alarachi, A and McNeely, HE and McKinnon, MC and McCabe, RE},
title = {Brain Fog and Cognitive Dysfunction in Posttraumatic Stress Disorder: An Evidence-Based Review.},
journal = {Psychology research and behavior management},
volume = {18},
number = {},
pages = {589-606},
pmid = {40093756},
issn = {1179-1578},
abstract = {The term "brain fog" has long been used both colloquially and in research literature in reference to various neurocognitive phenomenon that detract from cognitive efficiency. We define "brain fog" as the subjective experience of cognitive difficulties, in keeping with the most common colloquial and research use of the term. While a recent increase in use of this term has largely been in the context of the post-coronavirus-19 condition known as long COVID, "brain fog" has also been discussed in relation to several other conditions including mental health conditions such as post-traumatic stress disorder (PTSD). PTSD is associated with both subjective cognitive complaints and relative deficits on cognitive testing, but the phenomenology and mechanisms contributing to "brain fog" in this population are poorly understood. PTSD psychopathology across cognitive, affective and physiological symptom domains have been tied to "brain fog". Furthermore, dissociative symptoms common in PTSD also contribute to the experience of "brain fog". Comorbid physical and mental health conditions may also increase the risk of experiencing "brain fog" among individuals with PTSD. Considerations for the assessment of "brain fog" in PTSD as part of psychodiagnostic assessment are discussed. While standard psychological intervention for PTSD is associated with a reduction in subjective cognitive deficits, other cognitive interventions may be valuable when "brain fog" persists following PTSD remission or when "brain fog" interferes with treatment. Limitations of current research on "brain fog" in PTSD include a lack of consistent definition and operationalization of "brain fog" in the literature, as well as limited tools for measurement. Future research should address these limitations, as well as further evaluate the use of cognitive remediation as an intervention for "brain fog".},
}

@article {pmid40084919,
year = {2025},
author = {Baalbaki, N and Slob, EMA and Kazer, SW and I Abdel-Aziz, M and Bogaard, HJ and Golebski, K and Maitland-van der Zee, AH},
title = {The Omics Landscape of Long COVID-A Comprehensive Systematic Review to Advance Biomarker, Target and Drug Discovery.},
journal = {Allergy},
volume = {80},
number = {4},
pages = {932-948},
pmid = {40084919},
issn = {1398-9995},
support = {//Health~Holland/ ; },
mesh = {Humans ; *COVID-19/metabolism/genetics ; Biomarkers/metabolism ; SARS-CoV-2 ; Metabolomics ; *Drug Discovery ; Genomics ; Proteomics ; Post-Acute COVID-19 Syndrome ; },
abstract = {An estimated 10% of coronavirus disease (COVID-19) survivors suffer from persisting symptoms referred to as long COVID (LC), a condition for which approved treatment options are still lacking. This systematic review (PROSPERO: CRD42024499281) aimed to explore the pathophysiological mechanisms underlying LC and potential treatable traits across symptom-based phenotypes. We included studies with primary data, written in English, focusing on omics analyses of human samples from LC patients with persistent symptoms of at least 3 months. Our search in PubMed and Embase, conducted on January 8, 2024, identified 642 studies, of which 29 met the inclusion criteria after full-text assessment. The risk of bias was evaluated using the Joanna Briggs Institute appraisal tool. The synthesis of omics data, including genomics, transcriptomics, proteomics, metabolomics, and metagenomics, revealed common findings associated with fatigue, cardiovascular, pulmonary, neurological, and gastrointestinal phenotypes. Key findings included mitochondrial dysfunction, dysregulated microRNAs associated with pulmonary dysfunction, tissue impairment, blood-brain barrier disruption, coagulopathy, vascular dysfunction, microbiome disturbances, microbial-derived metabolite production and persistent inflammation. Limitations include cross-study heterogeneity and variability in sampling methods. Our review emphasizes the complexity of LC and the need for further longitudinal omics-integrated studies to advance the development of biomarkers and targeted treatments.},
}

Humans
*COVID-19/metabolism/genetics
Biomarkers/metabolism
SARS-CoV-2
Metabolomics
*Drug Discovery
Genomics
Proteomics
Post-Acute COVID-19 Syndrome

@article {pmid40083165,
year = {2025},
author = {Li, S and Dai, B and Hou, Y and Zhang, L and Liu, J and Hou, H and Song, D and Wang, S and Li, X and Zhao, H and Wang, W and Kang, J and Tan, W},
title = {Effect of pulmonary rehabilitation for patients with long COVID-19: a systematic review and meta-analysis of randomized controlled trials.},
journal = {Therapeutic advances in respiratory disease},
volume = {19},
number = {},
pages = {17534666251323482},
pmid = {40083165},
issn = {1753-4666},
mesh = {Humans ; *COVID-19/rehabilitation/physiopathology/complications/diagnosis ; Randomized Controlled Trials as Topic ; Quality of Life ; *Lung/physiopathology ; Treatment Outcome ; Exercise Tolerance ; Walk Test ; Respiratory Function Tests ; Time Factors ; Recovery of Function ; },
abstract = {BACKGROUND: Pulmonary rehabilitation (PR) has demonstrated efficacy in managing long COVID-19, underscoring the need to refine and tailor PR strategies for optimal patient outcomes.

OBJECTIVES: To evaluate the impact of PR on patients with long COVID-19 and to compare the efficacy of different types and durations of PR interventions.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES AND METHODS: We systematically searched randomized controlled trials (RCTs) of the effectiveness of PR in long COVID-19 patients published before April 2024. The primary outcomes were physical capacity assessed by the 6-minute walking test (6MWT), lung function measured by forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), health-related quality of life (HRQoL), and fatigue. Secondary outcomes were thirty-second sit-to-stand test (30STST), handgrip strength tests, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), dyspnea, depression, anxiety, perceived effort, and adverse events.

RESULTS: A total of 37 studies with 3363 patients were included. Compared to controls, PR improved physical capacity (6MWT, 30STST, handgrip), lung function (FEV1, FVC, MIP, MEP), HRQoL, fatigue, dyspnea, and anxiety but did not reach statistical significance for depression. Subgroup analyses of PR duration indicated that programs of ⩽4 weeks improved 6MWT; those between 4 and 8 weeks significantly improved 6MWT, lung function (FEV1, FVC), HRQoL, and reduced fatigue; and programs over 8 weeks improved HRQoL and reduced fatigue. Exercise type analysis revealed that breathing exercises improved 6MWT, lung function (FEV1, FVC), and HRQoL; multicomponent exercises enhanced 6MWT performance and reduced fatigue; the combination of both types improved 6MWT, FEV1 (L), FVC (%pred), HRQoL, and reduced fatigue.

CONCLUSION: PR improves physical capacity, lung function, and quality of life and alleviates dyspnea, fatigue, and anxiety in long COVID-19 patients. A 4- to 8-week PR program and a combination of both breath exercises and multicomponent training is most effective for managing long-term COVID-19 syndromes.

TRIAL REGISTRATION: PROSPERO ID: CRD42024455008.},
}

Humans
*COVID-19/rehabilitation/physiopathology/complications/diagnosis
Randomized Controlled Trials as Topic
Quality of Life
*Lung/physiopathology
Treatment Outcome
Exercise Tolerance
Walk Test
Respiratory Function Tests
Time Factors
Recovery of Function

@article {pmid40080079,
year = {2025},
author = {Li, D and Long, F and Zhang, S and Yu, B},
title = {Mechanisms and treatment progress of neurological diseases of COVID and L-C19 in children.},
journal = {Physiology international},
volume = {112},
number = {1},
pages = {12-32},
doi = {10.1556/2060.2025.00484},
pmid = {40080079},
issn = {2498-602X},
mesh = {Humans ; *COVID-19/complications/therapy ; Child ; *Immunoglobulins, Intravenous/therapeutic use/adverse effects ; *Nervous System Diseases/therapy/virology ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; },
abstract = {OBJECTIVE: Although SARS-CoV-2 primarily targets the respiratory system, there is evidence that it can also infect the central nervous system, especially in children, leading to neurological symptoms and long-term consequences. It is imperative to summarize the possible mechanisms, main symptoms, and treatments of neurological symptoms of COVID-19 in children.

METHODS: We performed a literature search using the PubMed online database to find studies investigating the mechanisms of COVID-19 infection of the central nervous system and therapies for COVID-19 neurological symptoms in children.

RESULTS: The main mechanisms of action of SARS-CoV-2 virus on the nervous system are direct invasion, systemic inflammation and molecular mimicry. Although the incidence of adverse reactions to intravenous IgG therapy (IVIG) varies greatly and the contraindications are not yet clear, IVIG has been shown to be clearly effective for the neurological symptoms of COVID-19 in children.

CONCLUSION: However, due to insufficient data, more clinical studies are still needed to confirm its safety and efficacy, further improve the treatment plan, and determine the appropriate dosage to better serve clinical practice.

SIGNIFICANCE: The specific regimen of IVIG treatment for COVID-19 in children was explored, which further improved the understanding of COVID-19 and L-C19 neurological diseases in children.},
}

Humans
*COVID-19/complications/therapy
Child
*Immunoglobulins, Intravenous/therapeutic use/adverse effects
*Nervous System Diseases/therapy/virology
SARS-CoV-2
*COVID-19 Drug Treatment

@article {pmid40079963,
year = {2025},
author = {Rudolph, AE and Al Akoury, N and Bogdanenko, N and Markus, K and Whittle, I and Wright, O and Haridy, H and Spinardi, JR and McLaughlin, JM and Kyaw, MH},
title = {Factors affecting the impact of COVID-19 vaccination on post COVID-19 conditions among adults: A systematic literature review.},
journal = {Human vaccines & immunotherapeutics},
volume = {21},
number = {1},
pages = {2474772},
pmid = {40079963},
issn = {2164-554X},
mesh = {Humans ; *COVID-19 Vaccines/administration & dosage/immunology ; *COVID-19/prevention & control/immunology ; *Vaccination ; Adult ; *Vaccine Efficacy ; SARS-CoV-2/immunology ; },
abstract = {This systematic literature review summarizes the evidence across 56 publications and pre-prints (January 2020-July 2023) with low-risk of bias based on JBI critical appraisal, that report adjusted estimates for the relationship between COVID-19 vaccination and Post-COVID-19 Condition (PCC) by timing of vaccination relative to infection or PCC-onset. Comparisons of adjusted vaccine effectiveness (aVE) against ≥1 PCC (vs. unvaccinated) across study characteristics known to impact PCC burden or VE against other COVID-19 endpoints were possible for 31 studies where vaccination preceded infection. Seventy-seven percent of pre-infection aVE estimates were statistically significant (range: 7%-95%). Statistically significant pre-infection aVE estimates were slightly higher for mRNA (range: 14%-84%) than non-mRNA vaccines (range: 16%-38%) and aVE ranges before and during Omicron overlapped. Our findings suggest that COVID-19 vaccination before SARS-CoV-2 infection reduces the risk of PCC regardless of vaccine type, number of doses received, PCC definition, predominant variant, and severity of acute infections included.},
}

Humans
*COVID-19 Vaccines/administration & dosage/immunology
*COVID-19/prevention & control/immunology
*Vaccination
Adult
*Vaccine Efficacy
SARS-CoV-2/immunology

@article {pmid40076527,
year = {2025},
author = {Sun, DS and Lien, TS and Chang, HH},
title = {Virus-Induced Pathogenic Antibodies: Lessons from Long COVID and Dengue Hemorrhage Fever.},
journal = {International journal of molecular sciences},
volume = {26},
number = {5},
pages = {},
pmid = {40076527},
issn = {1422-0067},
support = {104-2320-B-320 -009 -MY3, 107-2311-B-320-002-MY3, 111-2320-B320-006-MY3, 112-2320-B-320-007//National Science and Technology Council, Taiwan/ ; TCMMP104-06, TCMMP108-04, TCMMP 111-01, TCAS111-02, TCAS-112-02, TCAS113-04, TCRD112-033, TCRD113-041//Tzu-Chi Medical Foundation/ ; },
mesh = {Humans ; *COVID-19/immunology/virology ; *Severe Dengue/immunology/virology ; *Antibodies, Viral/immunology ; *Dengue Virus/immunology ; Antibody-Dependent Enhancement/immunology ; *SARS-CoV-2/immunology ; Autoantibodies/immunology ; Animals ; Antibodies, Neutralizing/immunology ; },
abstract = {Virus-induced antibodies represent a dual-edged sword in the immune response to viral infections. While antibodies are critical for neutralizing pathogens, some can paradoxically exacerbate disease severity through mechanisms such as antibody-dependent enhancement (ADE), autoantibody, and prolonged inflammation. Long coronavirus disease (COVID) and dengue hemorrhagic fever (DHF) exemplify conditions where pathogenic antibodies play a pivotal role in disease progression. Long COVID is associated with persistent immune dysregulation and autoantibody production, leading to chronic symptoms and tissue damage. In DHF, pre-existing antibodies against dengue virus contribute to ADE, amplifying viral replication, immune activation, and vascular permeability. This review explores the mechanisms underlying these pathogenic antibody responses, highlighting the shared pathways of immune dysregulation and comparing the distinct features of both conditions. By examining these studies, we identify key lessons for therapeutic strategies, vaccine design, and future research aimed at mitigating the severe outcomes of viral infections.},
}

Humans
*COVID-19/immunology/virology
*Severe Dengue/immunology/virology
*Antibodies, Viral/immunology
*Dengue Virus/immunology
Antibody-Dependent Enhancement/immunology
*SARS-CoV-2/immunology
Autoantibodies/immunology
Animals
Antibodies, Neutralizing/immunology

@article {pmid40075382,
year = {2025},
author = {Weigel, B and Inderyas, M and Eaton-Fitch, N and Thapaliya, K and Marshall-Gradisnik, S},
title = {Health-related quality of life in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition: a systematic review.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {318},
pmid = {40075382},
issn = {1479-5876},
support = {489798//Stafford Fox Medical Research Foundation/ ; 1199502//National Health and Medical Research Council/ ; 47107//Mason Foundation/ ; 49979//McCusker Charitable Foundation/ ; 4676//Buxton Foundation/ ; 4879//Henty Community/ ; 4579//Blake Beckett Trust Foundation/ ; 4570//Alison Hunter Memorial Foundation/ ; 4575//Change for ME Charity/ ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology ; *Quality of Life ; *COVID-19/complications/psychology ; SARS-CoV-2 ; },
abstract = {PURPOSE: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post COVID-19 Condition (PCC) are debilitating, chronic multi-systemic illnesses that require multidisciplinary care. However, people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) are often precluded from accessing necessary disability and social support services. These unmet care needs exacerbate the existing illness burdens experienced by pwME/CFS and pwPCC. To deliver appropriate care and optimise health outcomes for pwME/CFS and pwPCC, the development of evidence-based healthcare policies that recognise the disabling impacts of these illnesses must be prioritised. This systematic review summarises the health-related quality of life (HRQoL) of pwME/CFS and pwPCC when compared with healthy controls (HCs) to elucidate the impacts of these illnesses and guide healthcare policy reform.

METHODS: CINAHL, Embase, MEDLINE, PubMed, PsycINFO and the Web of Science Core Collection were systematically searched from 1st January 2003 to 23rd July 2024. Eligible publications included observational studies capturing quantitative HRQoL data among pwME/CFS or pwPCC when compared with HCs. The use of validated patient-reported outcome measures (PROMs) was mandatory. Eligible studies were also required to employ the most stringent diagnostic criteria currently available, including the Canadian Consensus Criteria or International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC (PROSPERO ID: CRD42024501309).

RESULTS: This review captured 16 studies, including eight studies among pwME/CFS, seven studies among pwPCC and one study among both illness cohorts. Most participants were female and middle-aged. All pwPCC had experienced prolonged COVID-19 symptoms for at least three months. When compared with HCs, all HRQoL domains were significantly impaired among pwME/CFS and pwPCC. Both illnesses had a salient impact on physical health, including pain and ability to perform daily and work activities. While direct comparisons between pwME/CFS and pwPCC were limited by inconsistencies in the PROMs employed, comparable impact trends across HRQoL domain scores were observed.

CONCLUSION: ME/CFS and PCC have similar, profound impacts on HRQoL that warrant access to multidisciplinary disability and social support services. Future research must harmonise HRQoL data collection and prioritise longitudinal investigations among pwME/CFS and pwPCC to characterise PCC subgroups (including those fulfilling ME/CFS criteria) and predictors of prognosis.},
}

Humans
*Fatigue Syndrome, Chronic/psychology
*Quality of Life
*COVID-19/complications/psychology
SARS-CoV-2

@article {pmid40074704,
year = {2025},
author = {Schwartz, J and Capistrano, K and Hussein, H and Hafedi, A and Shukla, D and Naqvi, A},
title = {Oral SARS-CoV-2 Infection and Risk for Long Covid.},
journal = {Reviews in medical virology},
volume = {35},
number = {2},
pages = {e70029},
pmid = {40074704},
issn = {1099-1654},
support = {R56DE033249//NIDCR/NIH/ ; R01EY033622//NEI/NIH/ ; R01DE027980//NIDCR/NIH/ ; R01 DE027980/DE/NIDCR NIH HHS/United States ; R56 DE033249/DE/NIDCR NIH HHS/United States ; /NH/NIH HHS/United States ; R01 EY033622/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/virology/complications/pathology/immunology ; *SARS-CoV-2/pathogenicity ; Dysbiosis/virology/microbiology ; Mouth Mucosa/virology/microbiology/immunology/pathology ; *Mouth Diseases/virology/microbiology ; Angiotensin-Converting Enzyme 2/genetics/metabolism ; Microbiota ; Post-Acute COVID-19 Syndrome ; Serine Endopeptidases ; },
abstract = {SARS-CoV-2 is an oral pathogen that infects and replicates in mucosal and salivary epithelial cells, contributing to oral post-acute sequelae COVID-19 (PASC) and other oral and non-oral pathologies. While pre-existing inflammatory oral diseases provides a conducive environment for the virus, acute infection and persistence of SARS-CoV-2 can also results in oral microbiome dysbiosis that further worsens poor oral mucosal health. Indeed, oral PASC includes periodontal diseases, dysgeusia, xerostomia, pharyngitis, oral keratoses, and pulpitis suggesting significant bacterial contributions to SARS-CoV-2 and oral tissue tropism. Dysbiotic microbiome-induced inflammation can promote viral entry via angiotensin-converting enzyme receptor-2 (ACE2), serine transmembrane TMPRSS2 and possibly other non-canonical pathways. Additionally, metabolites derived from a dysbiotic microbiome can alter the physiological and biochemical pathways related to the metabolism of lipids, carbohydrates, and amino acids. This may promote a pro-inflammatory microenvironment, leading to immune exhaustion, loss of tolerance, and susceptibility to a variety of oral pathogens, causing acute and later chronic inflammation. Microbial release of mimics of host metallopeptidases related to furin, ADAM17 (A disintegrin and metalloproteinase 17), and glycoprotein metabolites can further aid viral attachment to T cell immunoglobulin-like (TIMs), enhancing viral entry while simultaneously depressing oral mucosal immune resistance and clearance. Membrane reorganization characterised by neuroproteins, such as neuropilins, also functionally assists with SARS-CoV-2 entry and extends the pathogenesis of PASC from the oral cavity to the brain, gut, or other non-oral tissues. Thus, poor oral health, characterised by disrupted oral microbiomes can promote viral tropism, weaken antiviral resistance, and heightens susceptibility to SARS-CoV-2 infection. This immune dysfunction also increases the risk of additional viral infections, exacerbating oral conditions like periodontal and endodontic diseases. These persistent oral health issues can contribute to systemic inflammation, creating bidirectional effects between oral and non-oral tissues, potentially leading to Post-Acute Sequelae of COVID-19 (PASC).},
}

Humans
*COVID-19/virology/complications/pathology/immunology
*SARS-CoV-2/pathogenicity
Dysbiosis/virology/microbiology
Mouth Mucosa/virology/microbiology/immunology/pathology
*Mouth Diseases/virology/microbiology
Angiotensin-Converting Enzyme 2/genetics/metabolism
Microbiota
Post-Acute COVID-19 Syndrome
Serine Endopeptidases

@article {pmid40073162,
year = {2025},
author = {Taher, MK and Salzman, T and Banal, A and Morissette, K and Domingo, FR and Cheung, AM and Cooper, CL and Boland, L and Zuckermann, AM and Mullah, MA and Laprise, C and Colonna, R and Hashi, A and Rahman, P and Collins, E and Corrin, T and Waddell, LA and Pagaduan, JE and Ahmad, R and Jaramillo Garcia, AP},
title = {Global prevalence of post-COVID-19 condition: a systematic review and meta-analysis of prospective evidence.},
journal = {Health promotion and chronic disease prevention in Canada : research, policy and practice},
volume = {45},
number = {3},
pages = {112-138},
pmid = {40073162},
issn = {2368-738X},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; Prospective Studies ; SARS-CoV-2 ; Global Health ; Female ; *Survivors/statistics & numerical data ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: We investigated the prevalence of new or persistent manifestations experienced by COVID-19 survivors at 3 or more months after their initial infection, collectively known as post-COVID-19 condition (PCC).

METHODS: We searched four electronic databases and major grey literature resources for prospective studies, systematic reviews, authoritative reports and population surveys. A random-effects meta-analysis pooled the prevalence data of 22 symptoms and outcomes. The GRADE approach was used to assess the certainty of evidence. PROSPERO CRD42021231476.

RESULTS: Of 20 731 identified references, 194 met our inclusion criteria. These studies followed 483 531 individuals with confirmed COVID-19 diagnosis over periods of up to 2 years. Most focused on adults, nearly two-thirds were conducted in Europe and 63% were of high or moderate quality. The supplementary search identified 17 systematic reviews, five authoritative reports and four population surveys that reported on PCC prevalence. Our analysis revealed that more than half of COVID-19 survivors experienced one or more symptoms more than a year after their initial infection. The most common symptoms were fatiguedyspneamemory, sleep or concentration disturbances; depressionand pain. Limitation in returning to work was the most common outcome. Prevalence tended to be higher among females, individuals hospitalized during their initial infection and those who experienced severe COVID-19 illness.

CONCLUSION: PCC presents a significant health burden, affecting some groups more than others. This information will help inform health care system policies and services for people living with PCC and those caring for them.},
}

Humans
*COVID-19/epidemiology/complications
Prevalence
Prospective Studies
SARS-CoV-2
Global Health
Female
*Survivors/statistics & numerical data
Post-Acute COVID-19 Syndrome

@article {pmid40071259,
year = {2025},
author = {Velati, D and Puoti, M},
title = {Real-world experience with therapies for SARS-CoV-2: Lessons from the Italian COVID-19 studies.},
journal = {Le infezioni in medicina},
volume = {33},
number = {1},
pages = {64-75},
pmid = {40071259},
issn = {2532-8689},
abstract = {The therapeutic armamentarium that has been made available from the beginning of the emergency phase of the COVID-19 pandemic to date is briefly reviewed, and an overview of the real-world clinical evidence published by the Italian medical and scientific community during the last three years is presented herein. Prior to the introduction of a vaccine for SARS-CoV-2, several treatment options were implemented from the onset given the evidence that a "cytokine storm" was present during infection with SARS-CoV-2. However, with the exception of tocilizumab, baricitinib and perhaps anakinra, most studies with anti-cytokine biological agents in patients with severe COVID-19 did not show any significant clinical improvement or decrease in mortality at day 28. The same is true of several repurposed drugs including ivermectin, lactoferrin, interferon ß-1a, lopinavir/ritonavir alone or combined with hydroxychloroquine, and darunavir/ cobicistat, which did not show any benefits in clinical status or mortality. Treatment with neutralizing monoclonal antibodies (mAbs) for COVID-19 is changing continually with the evolution of new viral variants. In Italy, current indications for treatment of COVID-19 outpatients underline that the use of specific mAbs may vary over time depending on the prevalent SARS-CoV-2 variant and the sensitivity to the different mAbs available. Three antiviral drugs against SARS-CoV-2 were studied extensively and initially available in Italy: remdesivir, molnupiravir, and nirmaltrelvir/ritonavir, but at present the latter is the only oral antiviral for SARS-CoV-2 available in Italy. Several real-world studies for the use of nirmatrelvir/ ritonavir in the Italian population have been published. Among the current unmet needs, a clear and universal definition for long COVID along with treatments and prevention are still lacking as is clarity of the pathogenetic mechanisms responsible for it.},
}

@article {pmid40071133,
year = {2025},
author = {Monsalve, DM and Acosta-Ampudia, Y and Acosta, NG and Celis-Andrade, M and Şahin, A and Yilmaz, AM and Shoenfeld, Y and Ramírez-Santana, C},
title = {NETosis: A key player in autoimmunity, COVID-19, and long COVID.},
journal = {Journal of translational autoimmunity},
volume = {10},
number = {},
pages = {100280},
pmid = {40071133},
issn = {2589-9090},
abstract = {NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.},
}

@article {pmid40068974,
year = {2025},
author = {Emery, I and Rosen, C},
title = {Adult Long Coronavirus Disease 2019: Definition, Prevalence Pathophysiology, and Clinical Manifestations.},
journal = {Infectious disease clinics of North America},
volume = {39},
number = {2},
pages = {345-360},
doi = {10.1016/j.idc.2025.02.007},
pmid = {40068974},
issn = {1557-9824},
mesh = {Humans ; *COVID-19/physiopathology/epidemiology/complications ; SARS-CoV-2 ; Prevalence ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Adult ; Female ; Male ; },
abstract = {Long coronavirus disease 2019 (COVID-19) is a multisystem disorder with variable manifestations and duration. One in 10 people with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will develop some manifestation of long COVID-19. Currently, there is no one single etiologic factor for the symptoms and signs of long COVID-19 beyond exposure to the SARS-CoV-2 virus. There are multiple theories about the pathophysiology ranging from viral persistence, reactivation, autoimmunity, and immune depletion. Certain risk factors have been identified including female sex, severe acute/hospitalized COVID-19, previous infections with SARS-CoV-2, and absence of vaccinations.},
}

Humans
*COVID-19/physiopathology/epidemiology/complications
SARS-CoV-2
Prevalence
Risk Factors
Post-Acute COVID-19 Syndrome
Adult
Female
Male

@article {pmid40062993,
year = {2025},
author = {Cavarelli, M},
title = {Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID.},
journal = {Virologie (Montrouge, France)},
volume = {29},
number = {1},
pages = {57-68},
doi = {10.1684/vir.2025.1074},
pmid = {40062993},
issn = {1267-8694},
mesh = {Humans ; *COVID-19/virology/immunology/complications ; *SARS-CoV-2/physiology/immunology ; Post-Acute COVID-19 Syndrome ; Inflammation/virology ; },
abstract = {Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.},
}

Humans
*COVID-19/virology/immunology/complications
*SARS-CoV-2/physiology/immunology
Post-Acute COVID-19 Syndrome
Inflammation/virology

@article {pmid40062991,
year = {2025},
author = {Cavarelli, M},
title = {[Ghosts of the virus : unmasking the persistent threat of SARS-CoV-2 in Long COVID].},
journal = {Virologie (Montrouge, France)},
volume = {29},
number = {1},
pages = {41-53},
doi = {10.1684/vir.2025.1073},
pmid = {40062991},
issn = {1267-8694},
mesh = {Humans ; *COVID-19/virology/immunology/complications ; *SARS-CoV-2/physiology/immunology ; Post-Acute COVID-19 Syndrome ; Inflammation/virology ; },
abstract = {Long COVID has emerged as a debilitating condition, severely impacting the daily functioning and quality of life of affected individuals. The pathogenesis of Long COVID is complex and multifactorial, involving immune dysregulation, persistent inflammation, and potential reactivation of other pathogens. A key driver of Long COVID is the potential persistence of SARS-CoV-2 in various tissues beyond the respiratory tract, leading to the formation of viral reservoirs that contribute to ongoing symptoms, several months after initial infection. These reservoirs have been suggested in the gastrointestinal tract, central nervous system, cardiovascular system, and other tissues, often persisting months after the initial infection. Additionally, viral RNA and proteins in these tissues are associated with chronic inflammation and immune system disruptions, which are primary contributors to Long COVID symptoms. This article explores the mechanisms and consequences of SARS-CoV-2 persistence in respiratory and non-respiratory tissues, highlighting its impact on the immune system and underscoring critical areas for future research to improve outcomes for individuals suffering from Long COVID.},
}

Humans
*COVID-19/virology/immunology/complications
*SARS-CoV-2/physiology/immunology
Post-Acute COVID-19 Syndrome
Inflammation/virology

@article {pmid40051665,
year = {2025},
author = {Sakellaropoulos, SG and Sakellaropoulos, PG and Steinberg, BS and Rogers, C and Ismael, O and Scholl, EW and Mohammed, M and Mitsis, A and Patrinou, NG},
title = {Five Years of Long COVID Syndrome: An Updated Review on Cardiometabolic and Psychiatric Aspects.},
journal = {Cardiology research},
volume = {16},
number = {2},
pages = {81-85},
pmid = {40051665},
issn = {1923-2829},
abstract = {Five years after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there is still a significant number of people who have survived COVID-19 but never fully recovered from the disease. They go through an odyssey of doctor visits and a multitude of diagnostic tests, which ultimately do not provide concrete correlations and answers to the question of how exactly long COVID (LC) affects both physical and mental health, and performance. Often, not even highly technical and highly specialized methods, such as cardiac magnetic resonance imaging (MRI), can provide further explanation. Various research efforts continue to investigate the causes, effects and possible treatments of LC, particularly its impact on cognition and mental health. Patients with LC may experience persistent symptoms, but new symptoms also occur. Based on available studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does not only affect the pulmonary system, but nearly every major system and organ, from the brain and heart to the kidneys and immune system. What mechanisms could explain the persistent symptoms of LC and the inadequate recovery? How valuable is an early internal and neurological examination, particularly in the context of psychotherapy? In this review, we examined which factors could contribute to the persistence of LC symptoms and to what extent mitochondrial impairment by LC can explain the symptoms of LC.},
}

@article {pmid40046430,
year = {2024},
author = {Talkington, GM and Kolluru, P and Gressett, TE and Ismael, S and Meenakshi, U and Acquarone, M and Solch-Ottaiano, RJ and White, A and Ouvrier, B and Paré, K and Parker, N and Watters, A and Siddeeque, N and Sullivan, B and Ganguli, N and Calero-Hernandez, V and Hall, G and Longo, M and Bix, GJ},
title = {Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1465787},
pmid = {40046430},
issn = {1664-2295},
support = {TL1 TR003106/TR/NCATS NIH HHS/United States ; },
abstract = {One lingering effect of the COVID-19 pandemic created by SARS-CoV-2 is the emergence of Long COVID (LC), characterized by enduring neurological sequelae affecting a significant portion of survivors. This review provides a thorough analysis of these neurological disruptions with respect to cognitive dysfunction, which broadly manifest as chronic insomnia, fatigue, mood dysregulation, and cognitive impairments with respect to cognitive dysfunction. Furthermore, we characterize how diagnostic tools such as PET, MRI, EEG, and ultrasonography provide critical insight into subtle neurological anomalies that may mechanistically explain the Long COVID disease phenotype. In this review, we explore the mechanistic hypotheses of these neurological changes, which describe CNS invasion, neuroinflammation, blood-brain barrier disruption, and gut-brain axis dysregulation, along with the novel vascular disruption hypothesis that highlights endothelial dysfunction and hypoperfusion as a core underlying mechanism. We lastly evaluate the clinical treatment landscape, scrutinizing the efficacy of various therapeutic strategies ranging from antivirals to anti-inflammatory agents in mitigating the multifaceted symptoms of LC.},
}

@article {pmid40029778,
year = {2025},
author = {Wang, J and Xiong, Y and Song, Z and Li, Y and Zhang, L and Qin, C},
title = {Progress in research on osteoporosis secondary to SARS-CoV-2 infection.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.12573},
pmid = {40029778},
issn = {2576-2095},
support = {2060204//State Key Laboratory Special Fund/ ; 2022B1111020005//Key-Area Research and Development Program of Guangdong Province/ ; 2021-I2M-1-034,2023-I2M-2-001//Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences/ ; 82221004//The Foundation for Innovative Research Groups of the National Natural Science Foundation of China/ ; },
abstract = {The World Health Organization has declared that COVID-19 no longer constitutes a "public health emergency of international concern," yet the long-term impact of SARS-CoV-2 infection on bone health continues to pose new challenges for global public health. In recent years, numerous animal model and clinical studies have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to secondary osteoporosis. The mechanisms involved are related to the virus's direct effects on bone tissue, dysregulation of the body's inflammatory response, hypoxia, noncoding RNA imbalance, and metabolic abnormalities. Although these studies have unveiled the connection between SARS-CoV-2 infection and osteoporosis, current research is not comprehensive and in depth. Future studies are needed to evaluate the long-term effects of SARS-CoV-2 on bone density and metabolism, elucidate the specific mechanisms of pathogenesis, and explore potential interventions. This review aims to collate existing research literature on SARS-CoV-2 infection-induced secondary osteoporosis, summarize the underlying mechanisms, and provide direction for future research.},
}

@article {pmid40012912,
year = {2024},
author = {Naiditch, H and Betts, MR and Larman, HB and Levi, M and Rosenberg, AZ},
title = {Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1376654},
pmid = {40012912},
issn = {1664-3224},
support = {F32 MD019534/MD/NIMHD NIH HHS/United States ; T32 HL007563/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; Inflammation/immunology ; Cytokines/immunology/metabolism ; *Kidney Diseases/immunology ; },
abstract = {The emergence of the COVID-19 pandemic made it critical to understand the immune and inflammatory responses to the SARS-CoV-2 virus. It became increasingly recognized that the immune response was a key mediator of illness severity and that its mechanisms needed to be better understood. Early infection of both tissue and immune cells, such as macrophages, leading to pyroptosis-mediated inflammasome production in an organ system critical for systemic oxygenation likely plays a central role in the morbidity wrought by SARS-CoV-2. Delayed transcription of Type I and Type III interferons by SARS-CoV-2 may lead to early disinhibition of viral replication. Cytokines such as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor α (TNFα), some of which may be produced through mechanisms involving nuclear factor kappa B (NF-κB), likely contribute to the hyperinflammatory state in patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) cells, CD8+ T-cells, and B-cells, can contribute to disease severity and may reflect direct cytopathic effects of SARS-CoV-2 or end-organ sequestration. Direct infection and immune activation of endothelial cells by SARS-CoV-2 may be a critical mechanism through which end-organ systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation and microthrombi development can be seen in the lungs and other critical organs throughout the body, such as the heart, gut, and brain. The kidney may be among the most impacted extrapulmonary organ by SARS-CoV-2 infection owing to a high concentration of ACE2 and exposure to systemic SARS-CoV-2. In the kidney, acute tubular injury, early myofibroblast activation, and collapsing glomerulopathy in select populations likely account for COVID-19-related AKI and CKD development. The development of COVID-19-associated nephropathy (COVAN), in particular, may be mediated through IL-6 and signal transducer and activator of transcription 3 (STAT3) signaling, suggesting a direct connection between the COVID-19-related immune response and the development of chronic disease. Chronic manifestations of COVID-19 also include systemic conditions like Multisystem Inflammatory Syndrome in Children (MIS-C) and Adults (MIS-A) and post-acute sequelae of COVID-19 (PASC), which may reflect a spectrum of clinical presentations of persistent immune dysregulation. The lessons learned and those undergoing continued study likely have broad implications for understanding viral infections' immunologic and inflammatory consequences beyond coronaviruses.},
}

Humans
*COVID-19/immunology/complications
*SARS-CoV-2/immunology
Inflammation/immunology
Cytokines/immunology/metabolism
*Kidney Diseases/immunology

@article {pmid40011942,
year = {2025},
author = {Leitzke, M and Roach, DT and Hesse, S and Schönknecht, P and Becker, GA and Rullmann, M and Sattler, B and Sabri, O},
title = {Long COVID - a critical disruption of cholinergic neurotransmission?.},
journal = {Bioelectronic medicine},
volume = {11},
number = {1},
pages = {5},
pmid = {40011942},
issn = {2332-8886},
abstract = {BACKGROUND: Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with different symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently and make identification of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission.

METHODS: This paper reviews the current literature on the effects of blocked nicotinic acetylcholine receptors (nAChRs) on the main affected organ and cell systems and contrasts this with the unblocking effects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of post-vaccination syndrome (PVS). The fact that not only SARS-CoV-2 but numerous other viruses can bind to nAChRs is discussed under the assumption that numerous other post-viral diseases and autoimmune diseases (ADs) may also be due to impaired cholinergic transmission. We also present a case report that demonstrates changes in cholinergic transmission, specifically, the availability of α4β2 nAChRs by using (-)-[[18]F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a significant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Lastly, a descriptive analysis and evaluation were conducted on the results of a survey involving 231 users of LDTN.

RESULTS: A substantial body of research has emerged that offers a compelling explanation for the phenomenon of LC, suggesting that it can be plausibly explained because of impaired nAChR function in the human body. Following a ten-day course of transcutaneous nicotine administration, no enduring neuropathological manifestations were observed in the patient. This observation was accompanied by a significant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[[18]F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a significant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN.

CONCLUSIONS: In conclusion, based on current knowledge, LDTN appears to be a promising and safe procedure to relieve LC symptoms with no expected long-term harm.},
}

@article {pmid40004799,
year = {2025},
author = {Aliberti, A and Gasparro, R and Mignogna, M and Canfora, F and Spagnuolo, G and Sammartino, G and Coppola, N},
title = {Unveiling the Oral Lesions, Dysgeusia and Osteonecrosis Related to COVID-19: A Comprehensive Systematic Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {4},
pages = {},
pmid = {40004799},
issn = {2077-0383},
abstract = {Background/Objectives: The oral cavity has garnered increasing attention as a site for viral infection and related pathological manifestations in coronavirus disease-19. This article aims to provide a comprehensive overview of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-related oral manifestations, including taste disturbances, oral lesions and osteonecrosis. Methods: A search was conducted up to September 2024 according to PRISMA (Preferred Reporting Items for Systematic Reviews) guidelines using the databases PubMed and Scopus. All the observational, case-series, case-report and cross-sectional studies written in English on oral manifestations related to COVID-19 disease and long-COVID disease were included. All other types of studies and studies based on oral manifestation after COVID-19 vaccination and oral impairment due to lockdown were excluded. The risk of bias of included studies was assessed using the Joanna Briggs Appraisal checklist. Results: A total of 104 articles including 23 case-report, 15 case-series, 8 case-control, 18 cohort and 40 cross-sectional studies were selected. The results showed that patients with COVID-19 were found to have a significantly higher prevalence of xerostomia (45-74%) and dysgeusia (32-59%) compared to non-infected individuals. Regarding oral mucosal lesions, ulcers, candidiasis and herpes simplex infections were frequently observed. As for osteonecrosis, a significant number of patients with COVID-19-associated rhinomaxillary mucormycosis presented with maxillary osteonecrosis due to fungal infection, primarily mucormycosis. The methodological quality of most of the studies was moderate/high. Conclusions: COVID-19 has been associated with a range of oral manifestations. The complex interplay of viral infection, immune response, medication use and stress likely contributes to these oral complications. Early recognition and management of these oral manifestations are crucial for improving patient outcomes and developing targeted preventive and therapeutic strategies for COVID-19-related oral health issues.},
}

@article {pmid40003500,
year = {2025},
author = {Smyth, NJ and Blitshteyn, S},
title = {Language Matters: What Not to Say to Patients with Long COVID, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Other Complex Chronic Disorders.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {2},
pages = {},
pmid = {40003500},
issn = {1660-4601},
mesh = {Humans ; *Fatigue Syndrome, Chronic/psychology/therapy ; *COVID-19/psychology/therapy ; *Language ; Chronic Disease/psychology ; SARS-CoV-2 ; *Physician-Patient Relations ; },
abstract = {People with Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other complex chronic disorders consistently report having difficulty obtaining effective and compassionate medical care and being disbelieved, judged, gaslighted, and even dismissed by healthcare professionals. We believe that these adversarial interactions and language are more likely to arise when healthcare professionals are confronting complex chronic illnesses without proper training, diagnostic biomarkers, or FDA-approved therapies. These problematic conversations between practitioners and patients often involve specific words and phrases-termed the "never-words"-can leave patients in significant emotional distress and negatively impact the clinician-patient relationship and recovery. Seeking to prevent these destructive interactions, we review key literature on best practices for difficult clinical conversations and discuss the application of these practices for people with Long COVID, ME/CFS, dysautonomia, and other complex chronic disorders. We provide recommendations for alternative, preferred phrasing to the never-words, which can enhance therapeutic relationship and chronic illness patient care via compassionate, encouraging, and non-judgmental language.},
}

Humans
*Fatigue Syndrome, Chronic/psychology/therapy
*COVID-19/psychology/therapy
*Language
Chronic Disease/psychology
SARS-CoV-2
*Physician-Patient Relations

@article {pmid40002834,
year = {2025},
author = {Whitaker-Hardin, B and McGregor, KM and Uswatte, G and Lokken, K},
title = {A Narrative Review of the Efficacy of Long COVID Interventions on Brain Fog, Processing Speed, and Other Related Cognitive Outcomes.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
pmid = {40002834},
issn = {2227-9059},
abstract = {In the years following the global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19, researchers have become acutely aware of long-term symptomology associated with this disease, often termed long COVID. Long COVID is associated with pervasive symptoms affecting multiple organ systems. Neurocognitive symptoms are reported by up to 40% of long COVID patients, with resultant effects of loss of daily functioning, employment issues, and enormous economic impact and high healthcare utilization. The literature on effective, safe, and non-invasive interventions for the remediation of the cognitive consequences of long COVID is scarce and poorly described. Of specific interest to this narrative review is the identification of potential interventions for long COVID-associated neurocognitive deficits. Articles were sourced from PubMed, EBSCO, Scopus, and Embase following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published between the dates of January 2020 and 30 June 2024 were included in the search. Twelve studies were included in the narrative review, including a feasibility study, a pilot study, a case series, a case study, and an observational study, in addition to three randomized clinical trials and four interventional studies. Overall, treatment interventions such as cognitive training, non-invasive brain stimulation therapy, exercise rehabilitation, targeted pharmacological intervention, and other related treatment paradigms show promise in reducing long COVID cognitive issues. This narrative review highlights the need for more rigorous experimental designs and future studies are needed to fully evaluate treatment interventions for persistent cognitive deficits associated with long COVID.},
}

@article {pmid39997467,
year = {2025},
author = {Ayyoub, S and Dhillon, NK and Tura-Ceide, O},
title = {Genetics of Long COVID: Exploring the Molecular Drivers of Persistent Pulmonary Vascular Disease Symptoms.},
journal = {Infectious disease reports},
volume = {17},
number = {1},
pages = {},
pmid = {39997467},
issn = {2036-7430},
support = {CP17/00114, CPII22/00006)//Miguel Servet type grants from the Institute of Health Carlos III/ ; PI21/01212//Catalan Pneumology Foundation (FUCAP) and from the Institute of Health Carlos III/ ; 2024 FI-3 00065//AGAUR-FI ajuts Joan Oró, backed by the Secretariat of Universities and Research of the Department of Research and Universities of the Generalitat of Catalonia, and the European Social Plus Fund/ ; R01HL1528322//NIH Funding/ ; },
abstract = {Background/ Objectives: Long COVID or post-acute sequelae of SARS-CoV-2 infection (PASC) are symptoms that manifest despite passing the acute infection phase. These manifestations encompass a wide range of symptoms, the most common being fatigue, shortness of breath, and cognitive dysfunction. Genetic predisposition is clearly involved in the susceptibility of individuals to developing these persistent symptoms and the variation in the severity and forms. This review summarizes the role of genetic factors and gene polymorphisms in the development of major pulmonary vascular disorders associated with long COVID. Methods: A comprehensive review of current literature was conducted to examine the genetic contributions to pulmonary complications following SARS-CoV-2 infection. Studies investigating genetic polymorphisms linked to pulmonary hypertension, pulmonary thromboembolism, and pulmonary vascular endothelialitis were reviewed and summarized. Results: Findings show that specific genetic variants contribute to increased susceptibility to pulmonary vascular complications in long COVID patients. Variants associated with endothelial dysfunction, coagulation pathways, and inflammatory responses have been implicated in the development of pulmonary hypertension and thromboembolic events. Genetic predispositions influencing vascular integrity and immune responses appear to influence disease severity and progression. Conclusions: Understanding these mechanisms and genetic predispositions could pave the way for targeted therapeutic interventions to alleviate the burden on patients experiencing long COVID.},
}

@article {pmid39993991,
year = {2025},
author = {Mink, S and Wilhelm, F and Cadamuro, J and Reimann, P and Fraunberger, P},
title = {Anti-SARS-CoV-2 Antibodies in Long-COVID-Markers of Protection or Elevated Risk? A Systematic Review.},
journal = {Reviews in medical virology},
volume = {35},
number = {2},
pages = {e70027},
doi = {10.1002/rmv.70027},
pmid = {39993991},
issn = {1099-1654},
mesh = {Humans ; *COVID-19/immunology/virology/blood ; *Antibodies, Viral/blood/immunology ; *SARS-CoV-2/immunology ; Biomarkers/blood ; Risk Factors ; },
abstract = {Long-COVID affects a significant number of COVID-19 survivors, profoundly impacting daily life and work. Although research suggests a potential link between antibody levels and long-COVID risk, findings remain inconclusive. Understanding antibody dynamics could support the identification of patients at risk, improve long-COVID diagnosis, and guide protective strategies such as vaccination. Despite growing evidence, no systematic review has yet evaluated the current literature on this topic. We therefore aimed to synthesise and evaluate existing evidence on the association between anti-SARS-CoV-2 antibody titres and long-COVID, with the goal of clarifying their potential role in predicting long-COVID risk, guiding patient management, and informing future research directions. Studies published in PubMed/Medline databases between January 2020 and October 2024 were included without language restrictions. Studies on body fluids other than serum/blood were excluded. Study selection and quality assessment was conducted independently by two researchers. After screening 949 studies, 58 studies encompassing 53,739 individuals, and 7812 long-COVID patients, were included. Evidence was highly heterogenous but most studies reported an association between anti-SARS-CoV-2-spike antibodies and long-COVID, although the nature of the association appeared to be dependent on time from acute infection. Low anti-SARS-CoV-2-spike antibodies during acute COVID-19 were associated with increased risk of long-COVID. The association between low anti-SARS-CoV-2-spike antibodies during acute COVID-19 and long-COVID suggests that maintaining sufficiently high antibody levels may be protective. However, the current evidence level is low and further studies with sufficient power are required to confirm this association and to potentially determine protective cutoffs.},
}

Humans
*COVID-19/immunology/virology/blood
*Antibodies, Viral/blood/immunology
*SARS-CoV-2/immunology
Biomarkers/blood
Risk Factors

@article {pmid39990183,
year = {2025},
author = {Łukomska, E and Kloc, K and Kowalska, M and Matjaszek, A and Joshi, K and Scholz, S and Van de Velde, N and Beck, E},
title = {Healthcare Resource Utilization (HCRU) and Direct Medical Costs Associated with Long COVID or Post-COVID-19 Conditions: Findings from a Literature Review.},
journal = {Journal of market access & health policy},
volume = {13},
number = {1},
pages = {7},
pmid = {39990183},
issn = {2001-6689},
abstract = {Approximately 10-20% of individuals suffering from COVID-19 develop prolonged symptoms known as long COVID or post-COVID condition (LC). This review aimed to assess healthcare resource use (HCRU) and healthcare costs associated with LC. Because LC is not clearly defined and often remains undiagnosed, studies reporting on long-term follow-up of individuals with a COVID-19 diagnosis were also included. Among the 41 publications included, 36 reported on HCRU and 16 on costs. Individuals with LC had significantly elevated HCRU and healthcare costs vs. controls without a COVID-19 diagnosis over ≥15 months, with a 7.6-13.1% increase in total healthcare costs per person per month as assessed by difference-in-difference analysis. Among studies that did not specifically refer to LC, having a COVID-19 diagnosis was associated with a significant 4-10% increase in long-term total HCRU over 6-8 months and a 1.3- to 2.9-fold relative increase in total healthcare costs over 6 months. Due to the heterogeneity of the included studies, high-quality evidence is needed to better understand the economic burden of LC. In the absence of effective treatments, prioritizing the prevention of acute COVID-19, e.g., through vaccination, may be crucial for preventing LC and the associated long-term HCRU and medical spending.},
}

@article {pmid39984803,
year = {2025},
author = {Ivlev, I and Wagner, J and Phillips, T and Treadwell, JR},
title = {Interventions for Long COVID: A Narrative Review.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {39984803},
issn = {1525-1497},
support = {MSA-SOW#05-ECRI-ENG-11-07-2022/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
abstract = {Long COVID continues to impose a significant burden on COVID-19 survivors, presenting with diverse symptoms and clinical uncertainty. This review synthesized evidence from 97 studies, including 26 randomized controlled trials and 15 non-randomized comparative studies, which explored the effectiveness, comparative effectiveness, and potential risks of proposed interventions for managing common long COVID symptoms: fatigue, neurocognitive symptoms, anxiety, depression, and sleep issues. Our comprehensive analysis, encompassing English-language articles, gray literature, and feedback from 14 Key Informants (i.e., patients, caregivers, clinicians, payors, and researchers), reveals a persistently weak body of evidence, characterized by high imprecision and considerable uncertainty regarding the benefits and harms of the interventions. The studies examined a wide array of treatment categories, including multi-component rehabilitation, supplements, complementary treatments, prescription medications, and the COVID-19 vaccine. Key informants emphasized the critical need for establishing robust diagnostic criteria and utilizing functional outcomes while also highlighting significant barriers to care, including dismissive attitudes from healthcare providers, inadequate insurance coverage, and restricted access to specialty care. Given the evolving definitions of long COVID and the variable mechanisms of its management, our findings underscore the pressing need for further rigorous research to refine and validate effective treatment protocols. Until more definitive evidence is available, both clinicians and patients face substantial uncertainty in treatment decisions, with many resorting to self-treatment using costly and potentially ineffective options.},
}

@article {pmid39981885,
year = {2025},
author = {Zhang, Y and Chen, H and Li, Y and Luo, C and Zhu, Y and Zhou, X and Wang, R and He, J and Guo, H and Xu, X and Qiu, M and Li, J},
title = {Animal Models for Long COVID: Current Advances, Limitations, and Future Directions.},
journal = {Journal of medical virology},
volume = {97},
number = {2},
pages = {e70237},
doi = {10.1002/jmv.70237},
pmid = {39981885},
issn = {1096-9071},
mesh = {Animals ; *Disease Models, Animal ; *COVID-19/pathology/virology/epidemiology ; Humans ; Mice ; SARS-CoV-2/pathogenicity ; Mesocricetus ; Cricetinae ; Primates ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID (LC) represents a chronic, systemic, and often disabling condition that poses a significant ongoing threat to public health. Foundational scientific studies are needed to unravel the underlying mechanisms, with the ultimate goal of developing effective preventative and therapeutic strategies. Therefore, there is an urgent demand for animal models that can accurately replicate the clinical features of LC. This review integrates clinical epidemiological data to summarize the pathological changes in extrapulmonary systems involved in LC. Additionally, it critically examines the capacity of existing animal models, including nonhuman primates, genetically modified mice, and Syrian hamsters, to exhibit enduring postinfection symptoms that align with human clinical manifestations, and identifies key areas requiring further development. The objective is to offer insights that will aid in the development of next-generation animal models, thereby accelerating our understanding of how acute respiratory viral infections transition into chronic conditions, and ensuring preparedness for future pandemics.},
}

Animals
*Disease Models, Animal
*COVID-19/pathology/virology/epidemiology
Humans
Mice
SARS-CoV-2/pathogenicity
Mesocricetus
Cricetinae
Primates
Post-Acute COVID-19 Syndrome

@article {pmid39974559,
year = {2025},
author = {Ewing, AG and Salamon, S and Pretorius, E and Joffe, D and Fox, G and Bilodeau, S and Bar-Yam, Y},
title = {Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology.},
journal = {Medical review (2021)},
volume = {5},
number = {1},
pages = {66-75},
pmid = {39974559},
issn = {2749-9642},
abstract = {Long COVID, as currently defined by the World Health Organization (WHO) and other authorities, is a symptomatic condition that has been shown to affect an estimated 10 %-30 % of non-hospitalized patients after one infection. However, COVID-19 can also cause organ damage in individuals without symptoms, who would not fall under the current definition of Long COVID. This organ damage, whether symptomatic or not, can lead to various health impacts such as heart attacks and strokes. Given these observations, it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections. It is important to consider that many known adverse health outcomes, including heart conditions and cancers, can be asymptomatic until harm thresholds are reached. Many more medical conditions can be identified by testing than those that are recognized through reported symptoms. It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage, there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.},
}

@article {pmid39971694,
year = {2025},
author = {Tsang, MS and Zhou, IW and Zhang, AL and Xue, CC},
title = {Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials.},
journal = {Journal of integrative medicine},
volume = {23},
number = {2},
pages = {126-137},
doi = {10.1016/j.joim.2025.01.001},
pmid = {39971694},
issn = {2095-4964},
mesh = {Humans ; *Dyspnea/drug therapy/etiology ; *Drugs, Chinese Herbal/therapeutic use ; Randomized Controlled Trials as Topic ; *COVID-19/complications ; Fatigue/drug therapy ; SARS-CoV-2 ; Anxiety/drug therapy ; Depression/drug therapy ; Sleep Initiation and Maintenance Disorders/drug therapy ; Betacoronavirus ; },
abstract = {BACKGROUND: Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted.

OBJECTIVE: To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT).

SEARCH STRATEGY: World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023.

INCLUSION CRITERIA: Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment.

DATA EXTRACTION AND ANALYSIS: Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I[2].

RESULTS: Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I[2] = 68%) and low certainty.

CONCLUSION: CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; 23(2): 126-137.},
}

Humans
*Dyspnea/drug therapy/etiology
*Drugs, Chinese Herbal/therapeutic use
Randomized Controlled Trials as Topic
*COVID-19/complications
Fatigue/drug therapy
SARS-CoV-2
Anxiety/drug therapy
Depression/drug therapy
Sleep Initiation and Maintenance Disorders/drug therapy
Betacoronavirus

@article {pmid39967901,
year = {2024},
author = {Panesar, A and Gharanei, P and Khovanova, N and Young, L and Grammatopoulos, D},
title = {Thyroid function during COVID-19 and post-COVID complications in adults: a systematic review.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1477389},
pmid = {39967901},
issn = {1664-2392},
mesh = {Humans ; *COVID-19/complications/physiopathology ; *Thyroid Gland/physiopathology/virology ; *SARS-CoV-2 ; Adult ; *Thyroid Diseases/etiology/virology/physiopathology ; Thyroid Hormones ; },
abstract = {The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has presented multifaceted health challenges. COVID-19 primarily targets the respiratory system but also affects multiple organ systems, including the endocrine system. Emerging evidence suggests interactions between thyroid function, the acute phase of COVID-19, and the prolonged symptoms known as post-COVID sequalae or long COVID. Several studies have reported that COVID-19 can induce thyroid dysfunction, leading to conditions such as thyroiditis and alterations in thyroid hormone levels. The mechanisms through which SARS-CoV-2 affects the thyroid include direct viral infection of thyroid cells, leading to viral thyroiditis, which causes inflammation and transient or sustained thyroid dysfunction, as well as an excessive systemic immune response (cytokine storm). This is associated with elevated levels of cytokines, such as IL-6, that disrupt thyroid function and lead to nonthyroidal illness syndrome (NTIS). Medications administered during the acute illness phase, such as corticosteroids and antiviral drugs, can also impact thyroid hormone actions. The involvement of the thyroid gland in long COVID, or postacute sequelae of SARS-CoV-2 infection, is an area not well defined, with potential implications for understanding and managing this condition. Persistent low-grade inflammation affecting thyroid function over time can lead to ongoing thyroiditis or exacerbate pre-existing thyroid conditions. Viral infections, including SARS-CoV-2, can trigger or worsen autoimmune thyroid diseases, such as Hashimoto's thyroiditis and Graves' disease. Long COVID may disrupt the hypothalamic-pituitary-adrenal (HPA) axis, which can, in turn, affect the hypothalamic-pituitary-thyroid (HPT) axis, leading to abnormal thyroid function. This review was designed to systematically capture recent literature on COVID-19-related thyroid dysfunction in the adult population, the prognostic consequences of thyroid dysfunction during COVID-19, and the effects of thyroid dysfunction on patients with long COVID. A comprehensive search of PubMed and EMBASE databases was conducted. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed using the Critical Appraisal Skills Programme (CASP). A total of 53 studies met the inclusion criteria. The review summarises recent findings and provides an update of the current understanding of thyroid dysfunction in COVID-19-related spectrum of disorders, underscoring the complex nature of SARS-CoV-2 infection and its far-reaching impacts on human health.},
}

Humans
*COVID-19/complications/physiopathology
*Thyroid Gland/physiopathology/virology
*SARS-CoV-2
Adult
*Thyroid Diseases/etiology/virology/physiopathology
Thyroid Hormones

@article {pmid39967803,
year = {2025},
author = {Smadja, DM and Abreu, MM},
title = {Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1475376},
pmid = {39967803},
issn = {1662-4548},
abstract = {Neurodegenerative diseases (NDs) and Long COVID represent critical and growing global health challenges, characterized by complex pathophysiological mechanisms including neuronal deterioration, protein misfolding, and persistent neuroinflammation. The emergence of innovative therapeutic approaches, such as whole-body hyperthermia (WBH), offers promising potential to modulate underlying pathophysiological mechanisms in NDs and related conditions like Long COVID. WBH, particularly in fever-range, enhances mitochondrial function, induces heat shock proteins (HSPs), and modulates neuroinflammation-benefits that pharmacological treatments often struggle to replicate. HSPs such as HSP70 and HSP90 play pivotal roles in protein folding, aggregation prevention, and cellular protection, directly targeting pathological processes seen in NDs like Alzheimer's, Parkinson's, and Huntington's disease. Preliminary findings also suggest WBH's potential to alleviate neurological symptoms in Long COVID, where persistent neuroinflammation and serotonin dysregulation are prominent. Despite the absence of robust clinical trials, the therapeutic implications of WBH extend to immune modulation and the restoration of disrupted physiological pathways. However, the dual nature of hyperthermia's effects-balancing pro-inflammatory and anti-inflammatory responses-emphasizes the need for dose-controlled applications and stringent patient monitoring to minimize risks in vulnerable populations. While WBH shows potential interest, significant challenges remain. These include individual variability in response, limited accessibility to advanced hyperthermia technologies, and the need for standardized clinical protocols. Future research must focus on targeted clinical trials, biomarker identification, and personalized treatment strategies to optimize WBH's efficacy in NDs and Long COVID. The integration of WBH into therapeutic paradigms could mark a transformative step in addressing these complex conditions.},
}

@article {pmid39965723,
year = {2025},
author = {Foreman, L and Child, B and Saywell, I and Collins-Praino, L and Baetu, I},
title = {Cognitive reserve moderates the effect of COVID-19 on cognition: A systematic review and meta-analysis of individual participant data.},
journal = {Neuroscience and biobehavioral reviews},
volume = {171},
number = {},
pages = {106067},
doi = {10.1016/j.neubiorev.2025.106067},
pmid = {39965723},
issn = {1873-7528},
mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Reserve/physiology ; *Cognitive Dysfunction/etiology/physiopathology/psychology ; },
abstract = {Elucidating the factors that mitigate the effects of COVID-19 on cognitive function offers important insights for public health policy and intervention. This systematic review and individual participant data (IPD) meta-analysis assesses cognitive reserve (CR) as a potential moderator of post-COVID-19 cognitive dysfunction (PCCD). Under PRISMA-IPD guidelines, data searches were conducted via PubMed, PsycINFO, Scopus, and Embase, up to January 2023. Eligible studies included at least one cognitive assessment, CR proxy, and disease severity indicator. Of 5604 studies, 87 were eligible (10,950 COVID-19 cases; 78,305 controls), and IPD was obtained for 29 datasets (3919 COVID-19 cases; 8267 controls). Three-level random-effects meta-analyses indicated that CR had a moderate positive association (rsp =.29), and COVID-19 severity had a small negative association (rsp = -.07) with cognitive outcomes. These effects were moderated by a significant within-study interaction. Cognitive deficits following COVID-19 were 33 % smaller among high CR individuals, and 33 % greater among low CR individuals, relative to those with average CR. Population-based initiatives promoting reserve-building behaviors may alleviate the PCCD-related public health burden. REVIEW REGISTRATION: PROSPERO registration number: CRD42022360670.},
}

Humans
*COVID-19/complications/psychology
*Cognitive Reserve/physiology
*Cognitive Dysfunction/etiology/physiopathology/psychology

@article {pmid39960432,
year = {2025},
author = {Syed, AM and Karius, AK and Ma, J and Wang, PY and Hwang, PM},
title = {Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.},
journal = {Physiology (Bethesda, Md.)},
volume = {40},
number = {4},
pages = {0},
doi = {10.1152/physiol.00056.2024},
pmid = {39960432},
issn = {1548-9221},
support = {HL005101//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic/metabolism/physiopathology ; *Mitochondria/metabolism/pathology ; Animals ; COVID-19/metabolism ; },
abstract = {Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder of unclear etiology that affects many individuals worldwide. One of its hallmark symptoms is prolonged fatigue following exertion, a feature also observed in long COVID, suggesting an underlying dysfunction in energy production in both conditions. Here, mitochondrial dysfunction and its potential pathogenetic role in these disorders are reviewed.},
}

Humans
*Fatigue Syndrome, Chronic/metabolism/physiopathology
*Mitochondria/metabolism/pathology
Animals
COVID-19/metabolism