@article {pmid40736492,
year = {2025},
author = {Grad, R and Ebell, MH},
title = {Top 20 Research Studies of 2024 for Primary Care Physicians.},
journal = {American family physician},
volume = {112},
number = {1},
pages = {34-41},
pmid = {40736492},
issn = {1532-0650},
mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; *Physicians, Primary Care ; COVID-19 ; *Primary Health Care ; SARS-CoV-2 ; },
abstract = {This article summarizes the top 20 research studies of 2024 identified as POEMs (patient-oriented evidence that matters). Based on a network meta-analysis, the oral antibiotics most likely to be effective for community-acquired pneumonia are telithromycin (not available in the United States), azithromycin, amoxicillin-clavulanate, and the quinolones levofloxacin and nemonoxacin (not available in the United States). The oral antivirals molnupiravir and nirmatrelvir-ritonavir reduce hospitalizations in immunocompromised patients with COVID-19. In average-risk infants, a single dose of nirsevimab reduces hospitalizations due to respiratory syncytial virus. Amoxicillin with or without clavulanate is more effective than placebo for children with symptoms of acute sinusitis. Benzyl benzoate 25% is highly effective for scabies in adolescents and adults. Lactobacillus-containing probiotics reduce the incidence of recurrent urinary tract infections (UTIs) in premenopausal women with frequent UTIs. Low-dose amitriptyline is effective as second-line therapy for irritable bowel syndrome. For patients with uncomplicated gallstones, conservative management is a reasonable option. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are better than older drugs at improving patient-oriented outcomes for type 2 diabetes. Continuous or intermittent glucose monitoring is minimally effective for control of type 2 diabetes and can be harmful. Phentermine-topiramate and GLP-1 receptor agonists are the most effective drugs for promoting weight loss. Semaglutide is effective for secondary prevention of cardiovascular disease in people with obesity and no diabetes. SGLT-2 inhibitors and GLP-1 receptor agonists decrease cardiovascular death in older adults with type 2 diabetes and heart failure. Beta blockers do not prevent subsequent events after myocardial infarction in patients with preserved ejection fraction. For patients who do not quit smoking after a trial of varenicline or combined nicotine replacement therapy, a higher dose of either drug can increase quit rates. e-Cigarettes increase abstinence from smoking, but long-term vaping is a consequence for some. Oral naltrexone and acamprosate are safe and effective treatments for alcohol use disorder. Cognitive behavior therapy can reduce fatigue attributed to long COVID. New monoclonal antibodies for Alzheimer disease are harmful, expensive, and minimally effective. Clinicians may choose to deliver bad news in person or by telephone, using their judgment or patient preference to decide which is best for the patient.},
}

Humans
Anti-Bacterial Agents/therapeutic use
*Physicians, Primary Care
COVID-19
*Primary Health Care
SARS-CoV-2

@article {pmid40733521,
year = {2025},
author = {Mahajan, S and Mahajan, S and Patgiri, S},
title = {Association and Interaction of Epstein-Barr Virus with SARS-CoV-2 Infection-A Review.},
journal = {Viruses},
volume = {17},
number = {7},
pages = {},
doi = {10.3390/v17070903},
pmid = {40733521},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/virology/complications/immunology ; *Herpesvirus 4, Human/physiology ; *Epstein-Barr Virus Infections/virology/complications/drug therapy ; *SARS-CoV-2/physiology ; Virus Activation ; },
abstract = {Despite the significant decrease in SARS-CoV-2-related mortality, COVID-19 continues to impose a high public health burden due to the high rate of post-COVID-19 pathological conditions, broadly termed Long COVID, that continue for any period of time and are generally multisystemic. However, recent studies have strengthened the evidence that the reactivation of the Epstein-Barr virus (EBV) in the post-COVID-19 era has significantly contributed to the exacerbation and prolongation of Long COVID symptoms. The mechanism and pathophysiology of EBV reactivation in Long COVID patients still need further exploration due to limited studies. This review summarises the various studies linking EBV reactivation in Long COVID along with its pathophysiology and novel therapeutics for EBV in a post-COVID-19 era.},
}

Humans
*COVID-19/virology/complications/immunology
*Herpesvirus 4, Human/physiology
*Epstein-Barr Virus Infections/virology/complications/drug therapy
*SARS-CoV-2/physiology
Virus Activation

@article {pmid40729821,
year = {2025},
author = {Kell, DB and Kell, L and Kenny, LC and Merriel, A and Moore, JB and Pretorius, E},
title = {The roles of placental senescence, autophagy and senotherapeutics in the development and prevention of pre-eclampsia: A focus on ergothioneine.},
journal = {Journal of reproductive immunology},
volume = {171},
number = {},
pages = {104621},
doi = {10.1016/j.jri.2025.104621},
pmid = {40729821},
issn = {1872-7603},
abstract = {Cellular senescence is a well-established biological phenomenon in eukaryotes. It involves DNA damage, telomere shortening, a senescence-associated secretory phenotype (SASP), and the inability of cells to replicate. It is associated with ageing, and also with oxidative stress. Given the importance of oxidative stress in pre-eclampsia, there is considerable evidence, that we review, that senescence plays an important role in both normal placental development and in the development of both early- and late-term pre-eclampsia. Autophagy is capable of delaying or even reversing the development of senescence, and certain small molecules such as sulforaphane and spermidine can stimulate autophagy, including via the redox-sensitive transcription factor Nrf2. Ergothioneine is a thiohistidine antioxidant that is protective against a variety of cardiovascular and other diseases. Ergothioneine also interacts with Nrf2, and pre-eclampsia occurs far less frequently in individuals with higher plasma ergothioneine levels. Together, these elements provide a self-consistent, molecular and systems biology explanation for at least one mechanism by which ergothioneine may be protective against pre-eclampsia.},
}

@article {pmid40723876,
year = {2025},
author = {Richardson, E and Mo, CC and Calabretta, E and Corrado, F and Kocoglu, MH and Baron, RM and Connors, JM and Iacobelli, M and Wei, LJ and Benjamin, EJ and Rapoport, AP and Díaz-Ricart, M and Martínez-Mellado, AJ and Carlo-Stella, C and Richardson, PG and Moraleda, JM},
title = {Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19.},
journal = {Biomolecules},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/biom15071004},
pmid = {40723876},
issn = {2218-273X},
mesh = {Humans ; *Hematologic Neoplasms/drug therapy/complications/pathology ; *Polydeoxyribonucleotides/therapeutic use/pharmacology ; *COVID-19/complications/pathology/virology ; SARS-CoV-2 ; Hepatic Veno-Occlusive Disease/drug therapy ; *COVID-19 Drug Treatment ; Graft vs Host Disease/drug therapy ; Cytokine Release Syndrome/drug therapy ; *Fibrinolytic Agents/therapeutic use/pharmacology ; },
abstract = {Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide's potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection ("long-COVID"), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action.},
}

Humans
*Hematologic Neoplasms/drug therapy/complications/pathology
*Polydeoxyribonucleotides/therapeutic use/pharmacology
*COVID-19/complications/pathology/virology
SARS-CoV-2
Hepatic Veno-Occlusive Disease/drug therapy
*COVID-19 Drug Treatment
Graft vs Host Disease/drug therapy
Cytokine Release Syndrome/drug therapy
*Fibrinolytic Agents/therapeutic use/pharmacology

@article {pmid40721817,
year = {2025},
author = {Yogendra, R and Perlowski, A and Johng, B and Dahshan, H and Orr, C and Jeffers, D and Husain, K and Patterson, BK},
title = {Perioperative and anesthetic considerations for post-acute sequelae of COVID (PASC)/long COVID.},
journal = {Perioperative medicine (London, England)},
volume = {14},
number = {1},
pages = {80},
pmid = {40721817},
issn = {2047-0525},
abstract = {Post-acute sequelae of COVID (PASC), commonly known as long COVID, presents with a broad spectrum of medical conditions and symptoms persisting beyond 3 months post-SARS-CoV-2 infection, affecting over 18 million Americans and 65 million people worldwide. Despite its prevalence, to date, there are no specific clinical guidelines for the perioperative management of PASC patients. PASC is a complex, multisystemic condition leading to neurological, respiratory, and endocrine sequelae, potentially resulting from persistent viral presence, immune dysregulation, and/or end-organ damage. This manuscript discusses the implications of these sequelae on anesthesia practice, emphasizing the need for vigilance in pre-operative assessments to identify PASC and associated conditions through detailed patient history, understanding of off-label medication use, and familiarity with medical terminologies like POTS, MCAS, and brain fog. Key perioperative considerations include cautious use of anesthetics, especially in patients with neurological and cardiovascular complications. Pulmonary management strategies for PASC patients, such as lung-protective ventilation and non-invasive post-operative support, could mitigate any perioperative respiratory complications. Finally, we underscore the importance of a multidisciplinary approach to manage PASC patients effectively during surgery, advocating for personalized anesthetic plans and calling for more evidence-driven guidelines for this emerging patient group as research progresses.},
}

@article {pmid40717478,
year = {2025},
author = {Bajić, D and Todorović, N and Popović, ML and Plazačić, M and Mihajlović, A},
title = {Immunity's core reset: Synbiotics and gut microbiota in the COVID-19 era.},
journal = {Innate immunity},
volume = {31},
number = {},
pages = {17534259251362023},
doi = {10.1177/17534259251362023},
pmid = {40717478},
issn = {1753-4267},
abstract = {The gut microbiome plays a crucial role in shaping immune responses, and its connection to immunity has never been more relevant than in the COVID-19 era. The interaction between gut microbes and the immune system, known as microbiome-immunity crosstalk, influences both how the body responds to infections and how well it recovers. COVID-19, whether in its acute phase or lingering as long COVID, has been linked to disturbances in the gut microbiome. During infection, many patients experience dysbiosis-an imbalance in gut bacteria-that can contribute to immune dysfunction and excessive inflammation. This imbalance may not only worsen the severity of the disease but also prolong recovery, leading to persistent symptoms like fatigue, brain fog, and digestive issues. Long COVID, in particular, has been associated with ongoing immune dysregulation, where the body's defense system remains in a state of heightened activation, causing chronic inflammation. Given the strong link between gut health and immunity, there is growing interest in strategies to restore microbial balance. Synbiotics-combinations of probiotics (beneficial bacteria) and prebiotics (nutrients that support them)-are being explored as a potential therapeutic approach. By replenishing beneficial gut microbes, synbiotics may help regulate immune responses, reduce inflammation, and support overall recovery from COVID-19. Emerging research suggests that improving gut health could enhance the body's ability to fight infections and recover more efficiently. As we continue to understand the long-term impact of COVID-19, focusing on the gut microbiome offers a promising path forward. Supporting a balanced and diverse microbiome through diet, lifestyle, and targeted interventions like synbiotics may provide a natural way to strengthen immunity and improve health outcomes in both acute and long COVID cases.},
}

@article {pmid40708204,
year = {2025},
author = {Malerba, M and Purghè, B and Ragnoli, B and Manfredi, M and Baldanzi, G},
title = {Molecular profiling of exhaled breath condensate in respiratory diseases.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2537910},
doi = {10.1080/07853890.2025.2537910},
pmid = {40708204},
issn = {1365-2060},
mesh = {Humans ; Breath Tests/methods ; *COVID-19/metabolism/diagnosis ; Metabolomics/methods ; Proteomics/methods ; SARS-CoV-2 ; Exhalation ; Pulmonary Disease, Chronic Obstructive/diagnosis/metabolism ; Asthma/diagnosis/metabolism ; Mass Spectrometry/methods ; Biomarkers/analysis ; *Respiratory Tract Diseases/diagnosis/metabolism ; },
abstract = {BACKGROUND: Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways.

AIM: This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19).

RESULTS: We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors.

CONCLUSIONS: EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.},
}

Humans
Breath Tests/methods
*COVID-19/metabolism/diagnosis
Metabolomics/methods
Proteomics/methods
SARS-CoV-2
Exhalation
Pulmonary Disease, Chronic Obstructive/diagnosis/metabolism
Asthma/diagnosis/metabolism
Mass Spectrometry/methods
Biomarkers/analysis
*Respiratory Tract Diseases/diagnosis/metabolism

@article {pmid40707035,
year = {2025},
author = {Meagher, T},
title = {Long Covid in Year 5: Some Progress, Still Many Questions.},
journal = {Journal of insurance medicine (New York, N.Y.)},
volume = {52},
number = {2},
pages = {61-65},
doi = {10.17849/insm-52-2-1-5.2},
pmid = {40707035},
issn = {0743-6661},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Long Covid was first described in 2020. Five years later, progress in disease characterization has been considerable, and definitions continue to evolve. Several disease mechanisms are under study, and evidence for multiple endotypes is accumulating. No clinical biomarker has been identified, nor has an effective therapy been developed. Overlap with other post-infectious syndromes, particularly myalgic encephalomyelitis/chronic fatigue syndrome, is now more evident. For most individuals, symptoms of long Covid progressively disappear over time. Recurrent Covid-19 infections are now an important contributor to the pool of affected individuals. While symptoms limit activity in as many as 20%, inability to work is less common. The anticipated surge of disability claims from insured individuals has not materialized.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology
Fatigue Syndrome, Chronic
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid40696830,
year = {2025},
author = {Paulose, M and Adams, NN and Martin, KR and Grant, A},
title = {Lived Experiences of New-Onset Long Covid Pain and Its Impact on Health-Related Quality of Life. A Scoping Review of Current Evidence.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {4},
pages = {e70352},
doi = {10.1111/hex.70352},
pmid = {40696830},
issn = {1369-7625},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Quality of Life/psychology ; *COVID-19/complications/psychology ; *Chronic Pain/psychology/etiology ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long Covid (LC) is a multisystem condition that can cause persistent symptoms such as breathlessness, fatigue, cognitive problems and pain, with major effects on individuals and healthcare systems. Globally, nearly 400 million people have been affected. New-onset pain is among the most commonly reported symptoms and may develop into chronic pain, contributing to reduced health-related quality of life (HRQoL) and highlighting the need for appropriate care. Given its global prevalence, exploring how people experience new-onset LC pain and how it impacts their lives can help improve pain management and support services.

METHODS: A mixed-methods scoping review was conducted following the Joanna Briggs Institute (JBI) guidance and the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews (PRISMA-ScR). The review mapped and synthesised evidence from eligible primary research articles (quantitative, qualitative and mixed-methods) published in English between December 2019 and June 2024. Seven studies using cross-sectional, case-control and observational designs (n = 30 to 2507 participants) were included, with data collected from Europe and Asia.

RESULTS: While qualitative data on lived experience were limited, 69.5% of LC patients reported new-onset pain, most commonly musculoskeletal (MSK) pain (73.2%). Psychological symptoms such as post-traumatic stress disorder (PTSD) were also reported (38%). Pain medications were widely used. Findings suggest that new-onset LC pain affects physical, psychological and social well-being. No studies involving children or adolescents were identified, indicating a gap in the evidence on paediatric experiences of new-onset LC pain.

CONCLUSION: This review highlights major gaps in the literature, especially the lack of qualitative research on how people experience new-onset LC pain. Future research should explore these experiences in depth, with involvement from patients and the public, to inform the development of appropriate treatment and support strategies.

During the review process, opportunities to involve PPI were not fully explored due to limited awareness of how to support meaningful involvement in a scoping review, alongside time and resource constraints. Such involvement could have helped shape the review question, refine the search terms and interpret the findings in ways that better reflect lived experience. This is acknowledged as both a limitation and a learning point. PPI will be actively embedded in the next phases of the research.},
}

Humans
*Quality of Life/psychology
*COVID-19/complications/psychology
*Chronic Pain/psychology/etiology
SARS-CoV-2

@article {pmid40685660,
year = {2025},
author = {Davis, S and Mon-Yee, M and Sutton, A and Leaviss, J and Forsyth, JE and Burton, C},
title = {Cost effectiveness of non-pharmacological interventions for fatigue in patients with long-term conditions: a systematic literature review.},
journal = {Expert review of pharmacoeconomics & outcomes research},
volume = {},
number = {},
pages = {},
doi = {10.1080/14737167.2025.2537194},
pmid = {40685660},
issn = {1744-8379},
abstract = {INTRODUCTION: We aimed to assess the cost-effectiveness of non-pharmacological interventions for fatigue in patients with chronic conditions in the UK.

METHODS: This systematic review of cost-effectiveness studies aligns with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement. Data sources: Electronic databases and citation searches. Inclusion criteria: Studies including adults with one or more long-term health condition, either physical or mental. Exclusion criteria: Studies associated with cancer, long-COVID, post-viral fatigue, medically unexplained conditions, developmental disorders and injuries. Assessment: A single reviewer completed a two-stage sifting process.

RESULTS: Four studies met the inclusion criteria. They included patients with either multiple sclerosis or inflammatory rheumatic conditions, and assessed either cognitive behavioral therapy (CBT) or a personalized exercise programme (PEP). CBT was either dominated by usual care or had an incremental cost-effectiveness ratio (ICER) over £30,000. PEP dominated CBT, with the ICER for PEP versus usual care ranging from £13,159 to £35,424.

CONCLUSIONS: The economic literature on this topic is much more limited than the clinical effectiveness literature, both in terms of interventions and populations covered. Future research should focus on a de novo economic evaluation to identify interventions with a high potential to be cost-effective across multiple conditions.

REGISTRATION: PROSPERO (CRD42023440141).},
}

@article {pmid40684905,
year = {2025},
author = {Gershon, AS and Fung, D and Lam, GY},
title = {Diagnosing Respiratory Long COVID: a Practical Approach.},
journal = {Chest},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chest.2025.06.028},
pmid = {40684905},
issn = {1931-3543},
abstract = {Long COVID or post-COVID Condition, defined as the persistence of symptoms at least three months post-acute COVID-19 infection, is a novel condition where a definitive diagnostic marker and treatment has yet to be found. This condition, which has been estimated to impact more than 65 million individuals worldwide, manifests with multisystem involvement, most commonly presenting with fatigue, brain fog, dyspnea and/or cough. The burden of these symptoms can range from mild to severe with many patients reporting an inability to return to usual activities. Here, we present several hypothetical but clinically representative cases to allow discussion around how we approach the diagnosis of respiratory symptoms of Long COVID in those with and without chronic lung disease.},
}

@article {pmid40683613,
year = {2025},
author = {Chen, K and Wang, Z and Li, J and Xu, Y and Gu, S and Li, H and Li, J and Zhang, Y and Mao, N},
title = {Chronic inflammation in Long COVID relationship to autoimmune diseases.},
journal = {Autoimmunity reviews},
volume = {},
number = {},
pages = {103882},
doi = {10.1016/j.autrev.2025.103882},
pmid = {40683613},
issn = {1873-0183},
abstract = {The new coronavirus pandemic has been ongoing for nearly five years. In addition to the severe symptoms in the acute phase, it is accompanied by long-term complications and sequelae involving the respiratory, neurological, immune, circulatory, and gastrointestinal systems for several months or even years, which is called the Long COVID. Many studies have suggested that systemic chronic inflammation caused by residual viral components may be one of the pathophysiologic mechanisms of Long COVID. In this paper, we will review the autoimmune diseases caused by chronic inflammation. In particular, cytokine storminess, pro-inflammatory responses of inflammatory vesicles, mast cell activation syndrome, changes in the gut microbiota, molecular mimicry, reactivation of latent viruses, and coagulation abnormalities are among the pathways that contribute to autoimmune diseases, including Systemic Lupus Erythematosus, Guillain-Barré syndrome, rheumatoid arthritis. We intervene in the treatment of the disease with probiotics, immunoglobulins, the RECOVER clinical trial model, and immunomodulatory drugs. The aim is to enhance understanding of the pathophysiological mechanism of Long COVID and to provide a reference for the immunotherapy of patients.},
}

@article {pmid40680383,
year = {2025},
author = {Chen, TH and Jeng, TH and Lee, MY and Wang, HC and Tsai, KF and Chou, CK},
title = {Viral mitochondriopathy in COVID-19.},
journal = {Redox biology},
volume = {85},
number = {},
pages = {103766},
doi = {10.1016/j.redox.2025.103766},
pmid = {40680383},
issn = {2213-2317},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), disrupts cellular mitochondria, leading to widespread chronic inflammation and multi-organ dysfunction. Viral proteins cause mitochondrial bioenergetic collapse, disrupt mitochondrial dynamics, and impair ionic homeostasis, while avoiding antiviral defenses, including mitochondrial antiviral signaling. These changes drive both acute COVID-19 and its longer-term effects, known as "long COVID". This review examines new findings on the mechanisms by which SARS-CoV-2 affects mitochondria and for the impact on chronic immunity, long-term health risks, and potential treatments.},
}

@article {pmid40677535,
year = {2024},
author = {Mundra, P and Kailani, Z and Yaghoobi, M and Matthews, P and Tobis, M and Sadeghian, S and Albashir, S},
title = {Liver injury in post-acute COVID-19 syndrome: A systematic review and meta-analysis of early observational studies.},
journal = {Canadian liver journal},
volume = {7},
number = {4},
pages = {470-489},
pmid = {40677535},
issn = {2561-4444},
abstract = {BACKGROUND: Post-acute COVID-19 syndrome (PACS; long COVID) is characterized by persistent or delayed symptoms at least 4 weeks from acute COVID-19 infection. Given the well-documented incidence of liver injury in acute COVID-19, this systematic review aims to assess the odds of liver injury in earlier experiencers of PACS.

METHODS: Observational studies published prior to March 2022 were screened for data describing liver injury (defined per primary study) in patients with PACS.

RESULTS: A total of 2,117 abstracts and 35 full texts were screened, of which 26 met the inclusion criteria. The mean time since acute COVID infection across all studies was 195.5 days. Seven studies included COVID-negative control groups. Twenty-three studies measured lab findings, and nine studies measured imaging or elastography. Five studies were eligible for meta-analysis of odds ratios, which did not demonstrate a statistically significant difference in odds for liver injury in patients with PACS compared with COVID-negative patients (OR 2.22 [95% CI 0.51-9.61; p = 0.28]). Newcastle-Ottawa Scale assessments for all studies found 24 of 26 studies with high to very high risk of bias. ROBINS-E assessments for studies included in the meta-analysis found five of five studies with high to very high risk of bias.

CONCLUSIONS: Overall, our findings demonstrate no statistical difference in odds ratios of liver injury in patients with PACS compared with COVID-negative controls. As such, routine assessment and monitoring of liver injury in patients with PACS may not be required; however, higher quality data with lower risk of bias are required to make recommendations of higher certainty.},
}

@article {pmid40671020,
year = {2025},
author = {Wang, Y and Li, X and Hui, H and Yang, D},
title = {Efficacy and safety of traditional Chinese medicine for post-COVID-19 syndrome: a systematic review and meta-analysis.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {801},
pmid = {40671020},
issn = {1479-5876},
mesh = {Humans ; *Medicine, Chinese Traditional/methods/adverse effects ; *COVID-19/complications ; *Drugs, Chinese Herbal/therapeutic use/adverse effects ; Randomized Controlled Trials as Topic ; Treatment Outcome ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue/drug therapy ; Cough/drug therapy ; *COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Post-COVID-19 syndrome, characterized by persistent symptoms such as fatigue, dyspnea, cough, insomnia, and exercise intolerance, poses a significant challenge to global healthcare systems. Traditional Chinese Medicine (TCM) has been used to manage post-viral syndromes, but high-quality evidence for its effectiveness in post-COVID-19 recovery is limited. This study aimed to evaluate the clinical efficacy and safety of Chinese herbal medicine (CHM) in treating post-COVID-19 syndrome through a systematic review and meta-analysis of randomized controlled trials (RCTs).

METHODS: Five electronic databases (PubMed, Embase, Web of Science, Cochrane Library and CNKI) were systematically searched up to March 15, 2025. RCTs comparing CHM with placebo or usual care in patients with confirmed post-COVID-19 syndrome were included. Primary outcomes were symptom severity measured by the Visual Analogue Scale (VAS); secondary outcomes included relief rates of cough, fatigue, chest tightness, dyspnea, insomnia, and exercise intolerance. Data were pooled using a random-effects model, and heterogeneity was assessed using I[2] statistics.

RESULTS: Ten RCTs involving 2401 patients were included. CHM showed a greater reduction in VAS scores compared to controls (MD = -1.03; 95% CI -2.10 to 0.03; P = 0.0577), with higher heterogeneity (I[2] = 92%). Although this result did not reach conventional statistical significance, it suggests a potentially meaningful clinical trend favoring CHM. Subgroup analysis indicated both short-term and long-term CHM treatments improved VAS scores, with a stronger effect in long-term treatment. CHM significantly improved chest tightness (RR = 1.40; 95% CI 1.21-1.61; P < 0.0001; I[2] = 0%) and insomnia (RR = 1.23; 95% CI 1.03-1.47; P = 0.0216; I[2] = 0%). A trend toward improvement was observed in fatigue (RR = 1.58, 95% CI 0.95-2.64; P = 0.0781) and dyspnea (RR = 1.39, 95% CI 0.99-1.95; P = 0.0554), although these results did not reach statistical significance. No significant difference was observed in terms of 6-min walking distance (MD = 13.95 m, 95% CI -11.64 to 39.55; P = 0.2853). Adverse event rates were comparable between the herbal and control groups (RR = 0.72, 95% CI 0.49-1.07; P = 0.1052).

CONCLUSIONS: This meta-analysis indicates that Traditional Chinese Medicine (TCM) may help relieve certain post-COVID-19 symptoms, especially chest tightness and insomnia. Trends toward benefit were also noted for fatigue and dyspnea, though without statistical significance. Given the non-significant VAS results and high heterogeneity, these findings should be interpreted cautiously. Further large-scale, high-quality trials are needed to validate these outcomes and optimize treatment strategies.

https://www.crd.york.ac.uk/PROSPERO/home , CRD420251016442.},
}

Humans
*Medicine, Chinese Traditional/methods/adverse effects
*COVID-19/complications
*Drugs, Chinese Herbal/therapeutic use/adverse effects
Randomized Controlled Trials as Topic
Treatment Outcome
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Fatigue/drug therapy
Cough/drug therapy
*COVID-19 Drug Treatment

@article {pmid40670058,
year = {2025},
author = {Aretouli, E and Malik, M and Widmann, C and Parker, AM and Oh, ES and Vannorsdall, TD},
title = {Cognitive and mental health outcomes in long covid.},
journal = {BMJ (Clinical research ed.)},
volume = {390},
number = {},
pages = {e081349},
doi = {10.1136/bmj-2024-081349},
pmid = {40670058},
issn = {1756-1833},
mesh = {Humans ; *COVID-19/psychology/complications ; SARS-CoV-2 ; Mental Health ; *Cognitive Dysfunction/etiology ; Post-Acute COVID-19 Syndrome ; *Anxiety/etiology ; Risk Factors ; *Depression/etiology ; },
abstract = {Roughly one in five adults who meet criteria for long covid present with objective or subjective cognitive dysfunction or elevated symptoms of depression or anxiety lasting ≥12 weeks from an acute covid illness. These neuropsychiatric sequelae have considerable functional consequences at the level of the individual, society, and the broader economy. Neuropsychiatric long covid symptoms are thought to be causally diverse, and a range of risk factors as well as biological, psychological, and environmental mechanisms have been hypothesized to contribute to symptom development and persistence. When present, objective cognitive deficits tend to be modest for most individuals, with some evidence suggesting increased risk of dysfunction and decline specifically for older adults with a history of severe acute illness. Longitudinal data suggest a delayed emergence of psychiatric symptoms may occur in the weeks and months after an acute covid illness. Emerging research points to the early recovery period as a potential window of opportunity for intervention to alter patient trajectories, though evidence based treatment remains lacking.},
}

Humans
*COVID-19/psychology/complications
SARS-CoV-2
Mental Health
*Cognitive Dysfunction/etiology
Post-Acute COVID-19 Syndrome
*Anxiety/etiology
Risk Factors
*Depression/etiology

@article {pmid40663038,
year = {2025},
author = {Avais, LS and Pacheco, EC and Gomes, LPOZ and Baldani, MH and Martins, CM and Waldman, EA and Gonzalez, JPJ and Steen, TY and Borges, PKO},
title = {Oral Manifestations in the Post COVID-19 Condition: A Systematic Review With Meta-Analysis.},
journal = {Reviews in medical virology},
volume = {35},
number = {4},
pages = {e70057},
pmid = {40663038},
issn = {1099-1654},
support = {//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; //Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
mesh = {Humans ; *COVID-19/complications/virology ; *Mouth Diseases/epidemiology/etiology/virology ; SARS-CoV-2/pathogenicity ; *Taste Disorders/epidemiology/virology ; Prevalence ; Xerostomia ; },
abstract = {Post-COVID-19 condition, or Long COVID, is characterised by symptoms persisting or emerging beyond 12 weeks after acute infection. Among over 200 reported symptoms, oral manifestations such as taste loss and dry mouth have been identified. This systematic review reports the frequency and characteristics of these symptoms. Registered in PROSPERO and following PRISMA guidelines, the review included observational studies on COVID-19-positive adults presenting oral symptoms in the post-COVID-19 condition. A search in six databases (Medline/PubMed, Embase, Web of Science, Cochrane, SCOPUS, and LILACS) was conducted in January 2024. Risk of bias was assessed using Joanna Briggs Institute's critical appraisal tools, and certainty of evidence via GRADE. A meta-analysis using the inverse variance method estimated oral symptom prevalence. Of 4552 articles, 107 were included. Taste dysfunction persisted in 8% (95% CI 6%-10%) of patients beyond 12 weeks. Combined taste and smell alterations had a prevalence of 17% (95% CI 13%-21%). Less frequent symptoms included hyposalivation, periodontitis, mouth ulcers, tongue mucosal changes, facial tingling, sensitivity in the trigeminal nerve, difficulty swallowing, and lesions in the hard palate. Taste alterations were the most commonly reported symptom, underscoring the need for clinical recognition and appropriate management by oral health professionals. Additionally, the wide range of other oral manifestations highlights the necessity for further research to better understand their prevalence, underlying mechanisms, and clinical implications in post-COVID-19 patients.},
}

Humans
*COVID-19/complications/virology
*Mouth Diseases/epidemiology/etiology/virology
SARS-CoV-2/pathogenicity
*Taste Disorders/epidemiology/virology
Prevalence
Xerostomia

@article {pmid40656089,
year = {2024},
author = {Burkauskas, J and Branchi, I and Pallanti, S and Domschke, K},
title = {Anxiety in post-covid-19 syndrome - prevalence, mechanisms and treatment.},
journal = {Neuroscience applied..},
volume = {3},
number = {},
pages = {103932},
pmid = {40656089},
issn = {2772-4085},
abstract = {In addition to the general impact of the COVID-19 pandemic on anxiety-related mental state, anxiety and anxiety disorders have also been implicated within 'post-COVID-19 syndrome', i.e. following a SARS-CoV-2 infection. The present narrative review provides an update on the current state of knowledge on anxiety and anxiety disorders in the context of post-COVID-19 syndrome, on epidemiological, psychological, and biological factors that may contribute to anxiety following a SARS-CoV-2 infection, as well as on therapy options available for anxiety in the context of post-COVID-19 syndrome. A multi-step systematic literature search of PubMed and Web of Science databases was performed applying the following broad search terms: ("anxiety" OR "anxiety disorder") AND ("COVID" OR "COVID-19" OR "corona" OR "pandemic" OR "Post-COVID" OR "Long-COVID"). Eligible articles published until November 15, 2022 were included. Meta-analyses identified anxiety prevalence rates ranging from 16.6% to 29.6% after a SARS-CoV-2 infection. Premorbid anxiety has not reliably been shown to be associated with post-COVID-19 syndrome. Female sex, older age, severity of COVID-19 infection, hospitalization, reduced mobility, uncertainty, loneliness and low social support, anxiety sensitivity and cognitive inflexibility as well as biological factors such as immune dysregulation, alterations in the angiotensin system and hypothalamus-pituitary-adrenal axis activation have been identified as potential anxiety risk factors in the context of post-COVID-19 syndrome. Treatment options comprise pharmacotherapy with selective serotonin/noradrenaline reuptake inhibitors and (internet-/computer-based) cognitive behavioral psychotherapy, possibly augmented by mindfulness-based techniques, physical exercise and non-invasive brain stimulation. Provided corroboration of the currently suggested increased risk of anxiety in the context of post-COVID-19 syndrome by future large-scale, prospective studies, a standardized screening for anxiety in patients with a SARS-CoV-2 infection - particularly in individuals with risk factors - and a psychiatric consultation and liaison service should be established to provide preventive and therapeutic interventions as early as possible.},
}

@article {pmid40649991,
year = {2025},
author = {Hein, ZM and Thazin, and Kumar, S and Che Ramli, MD and Che Mohd Nassir, CMN},
title = {Immunomodulatory Mechanisms Underlying Neurological Manifestations in Long COVID: Implications for Immune-Mediated Neurodegeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {13},
pages = {},
pmid = {40649991},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/complications ; SARS-CoV-2/immunology ; *Neurodegenerative Diseases/immunology/etiology ; Blood-Brain Barrier/immunology ; Biomarkers ; Post-Acute COVID-19 Syndrome ; *Immunomodulation ; },
abstract = {The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood-brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus-immune-brain axis in long COVID and inform effective clinical management.},
}

Humans
*COVID-19/immunology/complications
SARS-CoV-2/immunology
*Neurodegenerative Diseases/immunology/etiology
Blood-Brain Barrier/immunology
Biomarkers
Post-Acute COVID-19 Syndrome
*Immunomodulation

@article {pmid40643301,
year = {2025},
author = {Beka, SG and Griffiths, RF and Myers, JA and Skirrow, PM},
title = {Appropriate Screening Tests to Assess Post-COVID-19 Cognitive Dysfunction in Aeromedical Settings.},
journal = {Aerospace medicine and human performance},
volume = {96},
number = {5},
pages = {414-424},
doi = {10.3357/AMHP.6500.2025},
pmid = {40643301},
issn = {2375-6322},
mesh = {Humans ; *COVID-19/complications/psychology ; *Cognitive Dysfunction/diagnosis/etiology ; *Pilots/psychology ; *Aerospace Medicine ; *Neuropsychological Tests ; SARS-CoV-2 ; Mass Screening ; },
abstract = {INTRODUCTION: Post-COVID-19, 10-20% of individuals may experience long-term symptoms (some having cognitive deficits), even after mild or nonsymptomatic infection. A sufficiently sensitive screening test of cognitive function, based on the typical cognitive effects of COVID-19 and skills considered most relevant to pilot performance, would be highly beneficial to be used alongside other performance checks. This study aimed to identify appropriate screening tests for post-COVID-19 cognitive dysfunction.

METHODS: Initially, a systematic search and narrative review identified 13 screening tools that are likely to be effective in screening pilots for post-COVID-19 neurocognitive impairment. Following a more in-depth evaluation of the identified tools, five tests including the Trail Making Test, Symbol Digit Modalities Test, Stroop Color Word Test, Psychomotor Vigilance Test, and Paced Auditory Serial Addition Test were chosen for a Delphi evaluation exercise. A two-round modified Delphi process was undertaken with international aviation medicine and psychology experts to obtain a consensus on which of the identified tests would be appropriate to screen for cognitive dysfunction in pilots.

RESULTS: Based on evaluation of literature review findings and Delphi consultation with subject matter experts, the Trail Making Test and Symbol Digit Modalities Test were identified as quick and suitable screening tests likely to detect post-COVID-19 cognitive dysfunction.

DISCUSSION: These tools are objective, have good utility, are available in multiple versions, and assess cognitive abilities relevant to pilot performance. Their use for screening in aeromedical examinations would be further supported by confirming their ability to reliably detect neurocognitive impacts associated with COVID-19. Beka SG, Griffiths RF, Myers JA, Skirrow PM. Appropriate screening tests to assess post-COVID-19 cognitive dysfunction in aeromedical settings. Aerosp Med Hum Perform. 2025; 96(5):414-424.},
}

Humans
*COVID-19/complications/psychology
*Cognitive Dysfunction/diagnosis/etiology
*Pilots/psychology
*Aerospace Medicine
*Neuropsychological Tests
SARS-CoV-2
Mass Screening

@article {pmid40434132,
year = {2025},
author = {Metcalfe, J and Scoullar, MJL and Whyler, NCA and Balkin, H and Tippett, E},
title = {Beyond time as the healer: action in long COVID treatment to improve patient outcomes.},
journal = {Internal medicine journal},
volume = {55},
number = {7},
pages = {1203-1207},
doi = {10.1111/imj.70099},
pmid = {40434132},
issn = {1445-5994},
mesh = {Humans ; *COVID-19/therapy ; *Quality of Life ; Patient-Centered Care ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Treatment Outcome ; },
abstract = {Long COVID is complex and disabling. Despite emerging therapies, the lack of guidelines and clinician awareness delays treatment. This paper highlights options available now to improve function and quality of life. We call for a symptom-focused, person-centred approach that incorporates lived experience and clinical judgement to bridge the gap between evidence and care. Time alone is not the answer.},
}

Humans
*COVID-19/therapy
*Quality of Life
Patient-Centered Care
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Treatment Outcome

@article {pmid40597822,
year = {2025},
author = {Münte, C and Glattacker, M and Müller, S and Zülke, AE and Heinze, M and Riedel-Heller, SG and Pieper, D and Jacke, C and Deckert, S and Neumann, A},
title = {Long COVID in people with mental health disorders: a scoping review.},
journal = {BMC psychiatry},
volume = {25},
number = {1},
pages = {669},
pmid = {40597822},
issn = {1471-244X},
mesh = {Humans ; *COVID-19/complications/psychology ; *Mental Disorders/psychology/epidemiology/complications/therapy ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long COVID, Post COVID Syndrome or PASC (post-acute sequelae of COVID-19), according to the World Health Organization (WHO), is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. The term Long COVID will be used throughout this review. Little is known about individuals with pre-existing mental health conditions experiencing Long COVID. This scoping review aims to provide an overview of these individuals, focusing on: 1) the course of mental disorders, 2) care needs, 3) utilization of healthcare services, and 4) psychosocial aspects, as outlined by the International Classification of Functioning (ICF).

METHODS: This review followed the JBI (Joanna Briggs Institute) methodology for scoping reviews and the PRISMA extension for scoping reviews. We included reports focusing on individuals with at least one pre-existing mental health diagnosis and Long COVID. Full-text reports in English or German were included, with no geographical limitations. Literature searches were conducted in PubMed, Embase, and PsycINFO on November 1, 2023, for records published between January 2020 and October 2023. Six reviewers participated in the screening process in pairs, independently conducting study selection and data extraction. Conflicts were resolved by consensus. Citation tracking was performed, and data were summarized narratively in tables.

RESULTS: From 4256 initial hits and citation tracking, 8 reports were included. The studies were heterogeneous, including chart reviews, case reports, cross-sectional, and longitudinal studies. Evidence on the impact of Long COVID on pre-existing mental health conditions was inconsistent. Most findings focused on the course of mental health disorders, ranging from symptom worsening to new symptoms of anxiety, depression, or insomnia. Evidence on mental health care needs, service utilization, and psychosocial aspects was limited.

CONCLUSION: Limited evidence suggests that individuals with pre-existing mental health disorders who experience Long COVID may be at an increased risk of worsening mental health. However, critical aspects such as care needs, service utilization, and psychosocial factors remain under-researched, highlighting the need for further studies on mental health care for Long COVID.

REVIEW REGISTRATION: Open Science Framework https://osf.io/tqexa .

CLINICAL TRIAL NUMBER: Not applicable.},
}

Humans
*COVID-19/complications/psychology
*Mental Disorders/psychology/epidemiology/complications/therapy
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid40589858,
year = {2025},
author = {Saikarthik, J and Saraswathi, I and Padhi, BK and Shamim, MA and Alzerwi, N and Alarifi, A and Gandhi, AP},
title = {Structural and functional neuroimaging of hippocampus to study adult neurogenesis in long COVID-19 patients with neuropsychiatric symptoms: a scoping review.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e19575},
pmid = {40589858},
issn = {2167-8359},
mesh = {Humans ; *COVID-19/complications/diagnostic imaging/physiopathology ; *Hippocampus/diagnostic imaging/physiopathology/pathology ; *Neurogenesis/physiology ; SARS-CoV-2 ; Adult ; *Functional Neuroimaging ; *Mental Disorders/diagnostic imaging/physiopathology ; Neuroimaging ; Magnetic Resonance Imaging ; },
abstract = {BACKGROUND: Worsening of neuropsychiatric and neurodegenerative disorders occurs in COVID-19. Impaired adult neurogenesis is linked to most of the neuropsychiatric symptoms and disorders.

AIM: The current scoping review identified and mapped the available evidence on adult neurogenesis in long COVID-19, at a global level following the JBI methodology for scoping reviews and followed the framework by Arksey and O'Malley.

METHOD: Original studies focusing on structural and functional neuroimaging of the hippocampus to study adult neurogenesis in long COVID-19 were included in the review. Studies published in English language with no restriction on the time of publication were searched using the specified search strategy in PubMed, Web of Science, Embase, and SCOPUS. Articles obtained from the database search were collated and uploaded into the Nested Knowledge AutoLit semi-automated systematic review platform for data extraction.

RESULTS: The current review provides evidence of the potential alterations in adult neurogenesis in long COVID-19 and its potential link to neuropsychiatric sequelae of long COVID-19, with further research required to validate this assertion.

CONCLUSION: This review proposes conceptual and methodological approaches for future investigations to address existing limitations and elucidate the precise role of adult neurogenesis in the pathophysiology and treatment of long COVID-19.},
}

Humans
*COVID-19/complications/diagnostic imaging/physiopathology
*Hippocampus/diagnostic imaging/physiopathology/pathology
*Neurogenesis/physiology
SARS-CoV-2
Adult
*Functional Neuroimaging
*Mental Disorders/diagnostic imaging/physiopathology
Neuroimaging
Magnetic Resonance Imaging

@article {pmid40583757,
year = {2025},
author = {Cornwell, WK and Levine, BD and Baptiste, D and Bhave, N and Desai, S and Dineen, E and Durstenfeld, M and Edward, J and Huang, M and Jacobsen, R and Kim, JH and Spatz, E and , },
title = {Exercise Intolerance and Response to Training in Patients With Postacute Sequelae of SARS-CoV2 (Long COVID): A Scientific Statement From the American Heart Association.},
journal = {Circulation},
volume = {},
number = {},
pages = {},
doi = {10.1161/CIR.0000000000001348},
pmid = {40583757},
issn = {1524-4539},
abstract = {The postacute sequelae of SARS-CoV-2, also known as Long COVID, may affect 10% to 25% of individuals diagnosed with SARS-CoV-2. More than 100 symptoms have been reported among patients with Long COVID, but almost all patients report severe fatigue, orthostatic intolerance, shortness of breath, and reductions in exercise tolerance. Emerging data suggest that cardiovascular deconditioning plays a major role in the development of this syndrome and that reductions in functional capacity among patients with Long COVID are comparable to reductions seen among individuals with cardiovascular deconditioning resulting from bed rest. Concern has been raised about the use of exercise training as part of the management strategy for patients with Long COVID. However, exercise training appropriately tailored to the patient with cardiovascular deconditioning may be an effective strategy to facilitate improvement in symptoms. This American Heart Association scientific statement provides a concise yet comprehensive overview of mechanisms contributing to development of Long COVID and methods by which exercise training may be applied to this unique patient population to alleviate symptoms and improve quality of life. In addition, methods of reintroducing exercise and return to play among athletes affected by COVID-19 are discussed.},
}

@article {pmid40582622,
year = {2025},
author = {Xu, K and He, W and Yu, B and Wang, JJ and Wu, J and Wang, DW},
title = {Unveiling the silent threat: COVID-19 and myocardial injury.},
journal = {Pharmacology & therapeutics},
volume = {},
number = {},
pages = {108904},
doi = {10.1016/j.pharmthera.2025.108904},
pmid = {40582622},
issn = {1879-016X},
abstract = {Since COVID-19 firstly appeared in 2019 December, it has been defined as an infectious disease mainly performing lung symptoms, which contracted more attention. However, more and more findings indicate myocardial injury appears in considerable proportion of COVID-19 patients (30 % - 50 %) not only but also major cause leading to the death in patients, many of whom may be even without severe respiratory symptoms. Meanwhile myocarditis after injecting vaccines has been paid more attention to globally which always performs uncontrollable inflammation and lead to death. Now myocardial injury has been a main complication in patients with long COVID-19, which is worthy of attention. Furthermore, myocardial injury or myocarditis is detectable and treatable. In order to abstract attention to myocardial injury associated with COVID-19 and provide more evidence and experience for patients who still suffer myocardial injury from COVID-19 vaccines or long COVID-19, the review comprehensively summarized previous researches from pathogenesis, clinical symptoms, diagnosis and treatment and emphasized the crucial role of RASS inhibitors especially ARBs.},
}

@article {pmid40180332,
year = {2025},
author = {Yang, OO},
title = {The immunopathogenesis of SARS-CoV-2 infection: Overview of lessons learned in the first 5 years.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {214},
number = {6},
pages = {1095-1104},
doi = {10.1093/jimmun/vkaf033},
pmid = {40180332},
issn = {1550-6606},
mesh = {Humans ; *COVID-19/immunology/pathology ; *SARS-CoV-2/immunology ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; CD8-Positive T-Lymphocytes/immunology ; Immunity, Cellular ; Immunity, Humoral ; },
abstract = {This review provides a broad overview of lessons learned in the five years since COVID-19 was identified. It is a bimodal disease, starting with an initially virus-driven phase, followed by resolution or ensuing inappropriate immune activation causing severe inflammation that is no longer strictly virus dependent. Humoral immunity is beneficial for preventing or attenuating the early stage, without benefit once the later stage begins. Neutralizing antibodies elicited by natural infection or vaccination are short-lived and highly vulnerable to viral sequence variation. By contrast, cellular immunity, particularly the CD8+ T cell arm, has a role in preventing or attenuating severe disease, is far less susceptible to viral variation, and is longer-lived than antibodies. Finally, an ill-defined phenomenon of prolonged symptoms after acute infection, termed "long COVID," is poorly understood but may involve various immunologic defects that are hyperactivating or immunosuppressive. Remaining issues include needing to better understand the immune dysregulation of severe disease to allow more tailored therapeutic interventions, developing antibody strategies that cope with the viral spike sequence variability, prolonging vaccine efficacy, and unraveling the mechanisms of long COVID to design therapeutic approaches.},
}

Humans
*COVID-19/immunology/pathology
*SARS-CoV-2/immunology
Antibodies, Neutralizing/immunology
Antibodies, Viral/immunology
CD8-Positive T-Lymphocytes/immunology
Immunity, Cellular
Immunity, Humoral

@article {pmid40575972,
year = {2025},
author = {Zhu, T and Li, X and Gao, S and Cui, R and Wang, J and Deng, Q},
title = {Successful salvage therapy of ruxolitinib on interstitial pneumonia after long COVID or post-COVID-19 syndrome with follicular lymphoma: two case reports and literature review.},
journal = {Chinese clinical oncology},
volume = {14},
number = {3},
pages = {35},
doi = {10.21037/cco-24-106},
pmid = {40575972},
issn = {2304-3873},
mesh = {Humans ; Nitriles ; *Pyrazoles/therapeutic use ; *COVID-19/complications ; Pyrimidines ; *Lymphoma, Follicular/complications/drug therapy ; *Salvage Therapy/methods ; Male ; SARS-CoV-2 ; Middle Aged ; Female ; *Lung Diseases, Interstitial/drug therapy/etiology ; COVID-19 Drug Treatment ; Aged ; Methylprednisolone/therapeutic use ; },
abstract = {BACKGROUND: Immunocompromised patients with B lymphocyte deficiency and hypogammaglobulinemia after anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory follicular lymphoma (FL) are at high risk of severe coronavirus disease 2019 (COVID-19) infection.

CASE DESCRIPTION: In our study, two patients with refractory FL had persistent COVID-19 infection after their anti-CD19 CAR T cell therapy. The patients were diagnosed with post-COVID-19 syndrome or COVID-19 with interstitial inflammation and persistent hypoxemia. The patients received molnupiravir and Paxlovid, along with methylprednisolone therapy when their interleukin (IL)-6 levels were high. No response was observed in interstitial inflammation, persistent hypoxemia, or persistent positive expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the level of IL-6 decreased after these therapies. These two patients subsequently received low-dose ruxolitinib (5 mg, twice daily) as salvage therapy in combination with a gradually reduced dosage of methylprednisolone. After 1-2 months of ruxolitinib therapy, persistent hypoxemia was relieved, and interstitial inflammation was significantly absorbed. At the same time, the SARS-CoV-2 detection was found to be negative.

CONCLUSIONS: Ruxolitinib might be a safe and effective alternative salvage therapy for patients with COVID-19 having interstitial inflammation and persistent hypoxemia without high cytokine levels and no response to corticosteroids.},
}

Humans
Nitriles
*Pyrazoles/therapeutic use
*COVID-19/complications
Pyrimidines
*Lymphoma, Follicular/complications/drug therapy
*Salvage Therapy/methods
Male
SARS-CoV-2
Middle Aged
Female
*Lung Diseases, Interstitial/drug therapy/etiology
COVID-19 Drug Treatment
Aged
Methylprednisolone/therapeutic use

@article {pmid40402473,
year = {2025},
author = {de Andrade, ML and do Monte, AL and Gerage, AM and Galliano, LM and Costa, EC and Ritti Dias, RM and Corrêa, FI},
title = {Effects of Physical Exercise on Functional Physical Performance in Individuals With Long COVID: A Systematic Review.},
journal = {Journal of cardiopulmonary rehabilitation and prevention},
volume = {45},
number = {4},
pages = {239-246},
pmid = {40402473},
issn = {1932-751X},
mesh = {Humans ; *COVID-19/rehabilitation/physiopathology/complications/psychology ; *Physical Functional Performance ; Quality of Life ; *Exercise Therapy/methods ; *Exercise/physiology ; SARS-CoV-2 ; Cardiorespiratory Fitness ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE: To analyze the effect of physical exercise on functional parameters in individuals with long coronavirus disease-2019 (COVID-19).

REVIEW METHODS: A search in MEDLINE, EMBASE, Web of Science, Scielo, and EBSCO was carried out in October 2022, and it was updated in June 2024. For inclusion, studies should have involved physical training without pulmonary rehabilitation, have involved individuals who had long COVID-19, and were prospective trials, clinical trials, or controlled trials. Two reviewers independently performed data extraction and assessed the risk of bias. Seven studies were reviewed, three of high methodological quality. Participants with long COVID-19 were hospitalized in two studies. Interventions lasted 2 to 16 weeks, with frequencies of 2 to 7 days per week, often involving resistance exercise. Strength improved in 67% of studies, cardiorespiratory fitness in 50%, and agility/mobility in 60%. Anxiety improved in 25% of studies, while depression improved in 75%. Quality of life improved across all studies, with dyspnea and fatigue improving in 40% and 80%, respectively.

SUMMARY: Results suggest potential benefits of exercise training for subjects with long COVID-19 in several outcomes, mainly in functional capacity, depression symptoms, quality of life, and fatigue.},
}

Humans
*COVID-19/rehabilitation/physiopathology/complications/psychology
*Physical Functional Performance
Quality of Life
*Exercise Therapy/methods
*Exercise/physiology
SARS-CoV-2
Cardiorespiratory Fitness
Post-Acute COVID-19 Syndrome

@article {pmid40566540,
year = {2025},
author = {Koutsiaris, AG and Karakousis, K},
title = {Long COVID Mechanisms, Microvascular Effects, and Evaluation Based on Incidence.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/life15060887},
pmid = {40566540},
issn = {2075-1729},
abstract = {Since the initial reports of Long COVID symptoms, numerous pathophysiological mechanisms have been proposed to explain them; nevertheless, no consensus has been reached. Some of these mechanisms are directly linked to microcirculation, while others are related indirectly. Those with a direct connection involve the respiratory system (such as pulmonary embolism), the cardiovascular system (including cardiac arrest, heart failure, myocardial inflammation, stroke, endothelial dysfunction, and microangiopathy), hematological conditions (like coagulopathy, deep vein thrombosis, microclots, and endothelial irregularities), and brain function. However, few of these mechanisms are grounded in quantitative data and fundamental physiological principles. Furthermore, diagnostic and therapeutic methods remain inadequate. This report provides a brief overview of these processes, focusing primarily on quantitative data, recently proposed mechanisms, and advances in microcirculation, with a special emphasis on the tissue blood supply reduction (TBSR or SR in short) mechanism. Then, the SR pathophysiological mechanism is assessed based on the total incidence rate of the Long COVID symptoms that can be directly attributed to this mechanism. The proposed SR mechanism can account for seven principal Long COVID symptoms with a total normalized incidence of 76%.},
}

@article {pmid40566294,
year = {2025},
author = {Rocha, DM and Pedroso, AO and Menegueti, MG and Silveira, RCCP and Sousa, LRM and Gir, E and Reis, RK},
title = {Predictors of Anxiety, Depression, and Stress in Long COVID: Systematic Review of Prevalence.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {6},
pages = {},
doi = {10.3390/ijerph22060867},
pmid = {40566294},
issn = {1660-4601},
support = {88881.657963/2021-01//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications ; *Anxiety/epidemiology/etiology ; *Depression/epidemiology/etiology ; Prevalence ; *Stress, Psychological/epidemiology/etiology ; Aged ; SARS-CoV-2 ; Adult ; },
abstract = {Anxiety, depression, and stress are prevalent psychosocial manifestations in Long COVID, and understanding their global impact can guide safe, effective, and evidence-based interventions. This study reviewed the literature to analyze the prevalence indicators and predictors of anxiety, depression, or stress experienced by adults and older adults with Long COVID. This systematic prevalence review was conducted using the databases MEDLINE via PubMed[®], CINAHL-EBSCO, Web of Science, Scopus, EMBASE, LILACS, and BDENF. Observational studies that assessed anxiety, depression, or perceived stress in adults and older adults with Long COVID were included, with no restrictions on time or language. Two reviewers independently conducted the selection process. Full texts were analyzed for their eligibility potential. Methodological quality was assessed using the JBI Critical Appraisal Checklist for Studies. Ten observational studies with moderate methodological quality were included. Anxiety and depression were the most prevalent psychosocial symptoms in Long COVID, reported in mild, moderate, and severe cases of COVID-19 infection. Prevalence rates reached up to 47.8% for anxiety, 37.3% for depression, and 23% for stress. The combined analysis revealed a pooled prevalence of 15.3% (95% CI: 10.8% to 20.2%). Being female, having pre-existing mental disorders or associated clinical comorbidities, experiencing severe infection in the acute phase, and receiving intensive care were predictors of greater mental burden. The experience of anxiety, depression, and stress in prolonged COVID-19 was reported in countries with different income levels and was disproportionately experienced, especially by women and individuals with associated clinical conditions or psychopathological comorbidities.},
}

Humans
*COVID-19/psychology/epidemiology/complications
*Anxiety/epidemiology/etiology
*Depression/epidemiology/etiology
Prevalence
*Stress, Psychological/epidemiology/etiology
Aged
SARS-CoV-2
Adult

@article {pmid40564201,
year = {2025},
author = {Hemat Jouy, S and Tonchev, H and Mostafa, SM and Mahmoud, AM},
title = {Post-COVID Metabolic Fallout: A Growing Threat of New-Onset and Exacerbated Diabetes.},
journal = {Biomedicines},
volume = {13},
number = {6},
pages = {},
doi = {10.3390/biomedicines13061482},
pmid = {40564201},
issn = {2227-9059},
support = {1R01HL161386-04/NH/NIH HHS/United States ; 1R00HL140049-03/NH/NIH HHS/United States ; },
abstract = {Emerging evidence highlights the profound and lasting impact of severe illnesses such as COVID-19, particularly among individuals with underlying comorbidities. Patients with pre-existing conditions like diabetes mellitus (DM) are disproportionately affected, facing heightened risks of both disease exacerbation and the onset of new complications. Notably, the convergence of advanced age and DM has been consistently associated with poor COVID-19 outcomes. However, the long-term metabolic consequences of SARS-CoV-2 infection, especially its role in disrupting glucose homeostasis and potentially triggering or worsening DM, remain incompletely understood. This review synthesizes current clinical and experimental findings to clarify the bidirectional relationship between COVID-19 and diabetes. We critically examine literature reporting deterioration of glycemic control, onset of hyperglycemia in previously non-diabetic individuals, and worsening of metabolic parameters in diabetic patients after infection. Furthermore, we explore proposed mechanistic pathways, including pancreatic β-cell dysfunction, systemic inflammation, and immune-mediated damage, that may underpin the development or progression of DM in the post-COVID setting. Collectively, this work underscores the urgent need for continued research and clinical vigilance in managing metabolic health in COVID-19 survivors.},
}

@article {pmid40563736,
year = {2025},
author = {Doskas, T and Vavougios, GD and Kormas, C and Kokkotis, C and Tsiptsios, D and Spiliopoulos, KC and Tsiakiri, A and Christidi, F and Aravidou, T and Dekavallas, L and Kazis, D and Dardiotis, E and Vadikolias, K},
title = {Neurocognitive Impairment After COVID-19: Mechanisms, Phenotypes, and Links to Alzheimer's Disease.},
journal = {Brain sciences},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/brainsci15060564},
pmid = {40563736},
issn = {2076-3425},
abstract = {BACKGROUND/OBJECTIVES: SARS-CoV-2 can affect the central nervous system directly or indirectly. AD shares several similarities with long COVID cognitive impairment on a molecular and imaging level, as well as common risk factors. The objective of this review is to evaluate the incidence of post-acute COVID-19 cognitive impairment. Secondarily, we aim to determine if neuroinflammation in COVID-19 survivors may be associated with the onset of neurological disease, with a focus on Alzheimer's disease (AD).

METHODS: literature search up to March 2025 on the prevalence of cognitive deficits in COVID-19 survivors, underlying pathophysiology and associations with neurological disorders.

RESULTS: a wide array of neuropsychiatric manifestations is associated with COVID-19; executive function, memory, and attention are the most frequently reported neurocognitive deficits, regardless of COVID-19 severity. There are associations between the risks for cognitive deficits post-infection with the age of the patients and the severity of the disease. Increasing evidence suggests that neurocognitive deficits are associated with the onset of neurological and neuropsychiatric disease in COVID-19 survivors.

CONCLUSIONS: clinicians caring for COVID-19 survivors should actively investigate neurocognitive sequelae, particularly for patients with increased risk for cognitive deficits.},
}

@article {pmid40552782,
year = {2025},
author = {Xu, Y and Xu, JW and Wu, Y and Rong, LJ and Ye, L and Franco, OH and Chien, CW and Feng, XR and Chen, JY and Tung, TH},
title = {Prevalence and prognosis of sarcopenia in acute COVID-19 and long COVID: a systematic review and meta-analysis.},
journal = {Annals of medicine},
volume = {57},
number = {1},
pages = {2519678},
doi = {10.1080/07853890.2025.2519678},
pmid = {40552782},
issn = {1365-2060},
mesh = {Humans ; *Sarcopenia/epidemiology ; *COVID-19/complications/epidemiology/mortality ; Prevalence ; Prognosis ; SARS-CoV-2 ; Length of Stay/statistics & numerical data ; Hospitalization/statistics & numerical data ; },
abstract = {BACKGROUND: A comprehensive investigation delineating the prevalence of sarcopenia across different infection phases, from acute COVID-19 to long COVID, is lacking. Meanwhile, the relationship between sarcopenia and adverse outcomes among COVID-19 patients remains inconsistent.

MATERIALS AND METHODS: A systematic search of MEDLINE/PubMed, Embase, Cochrane Library, Web of Science, and Scopus, before 22nd February 2025, was conducted to identify studies assessing sarcopenia prevalence in acute COVID-19 and long COVID. Random effects meta-analyses were performed to estimate the pooled prevalence of sarcopenia for acute COVID-19 and long COVID patients. Subgroup analyses stratified by assessment tool, region, income, hospitalization status, and age were performed. The associations between sarcopenia and COVID-19-related clinical outcomes were further quantified.

RESULTS: A total of 39 studies with 6,982 individuals were included. The pooled prevalence of sarcopenia was 48.7% (95% confidence interval (CI): 39.6-57.9%) in acute COVID-19 and 23.5% (95% CI: 12.7-39.4%) in long COVID. In acute COVID-19 patients, sarcopenia was not significantly associated with length of stay (mean difference = 2.215, 95% CI: -0.004 to 4.433), mechanical ventilation (Odds ratio (OR) = 1.80, 95% CI: 0.84-3.85), admission to the intensive care unit (OR = 1.05, 95% CI: 0.63-1.77), or mortality (OR = 1.41, 95% CI: 0.86-2.32), but was significantly associated with tracheostomy (OR = 2.48, 95% CI: 1.28-4.82).

CONCLUSION: In conclusion, our findings indicate that sarcopenia is highly prevalent in acute COVID-19 and persists in a substantial proportion of long COVID patients, suggesting prolonged muscle loss beyond the acute phase. Future well-designed studies are needed to further investigate the association between sarcopenia and short-term and long-term prognostic outcomes in both acute and long COVID patients.},
}

Humans
*Sarcopenia/epidemiology
*COVID-19/complications/epidemiology/mortality
Prevalence
Prognosis
SARS-CoV-2
Length of Stay/statistics & numerical data
Hospitalization/statistics & numerical data

@article {pmid40549427,
year = {2025},
author = {Luo, X and Li, Y and Xu, J and Zheng, Z and Ying, F and Huang, G},
title = {AI in Medical Questionnaires: Innovations, Diagnosis, and Implications.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e72398},
doi = {10.2196/72398},
pmid = {40549427},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; Surveys and Questionnaires ; COVID-19/epidemiology ; *Mental Disorders/diagnosis ; SARS-CoV-2 ; },
abstract = {This systematic review aimed to explore the current applications, potential benefits, and issues of artificial intelligence (AI) in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe. The World Health Organization reports that >1 billion people worldwide experience mental disorders, with the prevalence of depression and anxiety among children and adolescents at 2.6% and 6.5%, respectively. However, commonly used clinical questionnaires such as the Hamilton Depression Rating Scale and the Beck Depression Inventory suffer from several problems, including the high degree of overlap of symptoms of depression with those of other psychiatric disorders and a lack of professional supervision during administration of the questionnaires, which often lead to inaccurate diagnoses. In the wake of the COVID-19 pandemic, the health care system is facing the dual challenges of a surge in patient numbers and the complexity of mental health issues. AI technology has now been shown to have great promise in improving diagnostic accuracy, assisting clinical decision-making, and simplifying questionnaire development and data analysis. To systematically assess the value of AI in medical questionnaires, this study searched 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure) for the period from database inception to September 2024. Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed significant advantages in assessment, such as distinguishing myalgic encephalomyelitis or chronic fatigue syndrome from long COVID-19 with 92.18% accuracy. In questionnaire development, natural language processing using generative models such as ChatGPT was used to construct culturally competent scales. In terms of disease prediction, one study had an area under the curve of 0.790 for cataract surgery risk prediction. Overall, 24 AI technologies were identified, covering traditional algorithms such as random forest, support vector machine, and k-nearest neighbor, as well as deep learning models such as convolutional neural networks, Bidirectional Encoder Representations From Transformers, and ChatGPT. Despite the positive findings, only 21% (3/14) of the studies had entered the clinical validation phase, whereas the remaining 79% (11/14) were still in the exploratory phase of research. Most of the studies (10/14, 71%) were rated as being of moderate methodological quality, with major limitations including lack of a control group, incomplete follow-up data, and inadequate validation systems. In summary, the integrated application of AI in medical questionnaires has significant potential to improve diagnostic efficiency, accelerate scale development, and promote early intervention. Future research should pay more attention to model interpretability, system compatibility, validation standardization, and ethical governance to effectively address key challenges such as data privacy, clinical integration, and transparency.},
}

Humans
*Artificial Intelligence
Surveys and Questionnaires
COVID-19/epidemiology
*Mental Disorders/diagnosis
SARS-CoV-2

@article {pmid40543387,
year = {2025},
author = {Beuren, T and Ferrari, F and Franzoni, LT and Goulart, CDL and Val, F and Cipriano, G and Stein, R},
title = {Exploring the interplay between host genetics and acute and long COVID: A narrative review.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100708},
doi = {10.1016/j.clinsp.2025.100708},
pmid = {40543387},
issn = {1980-5322},
abstract = {Over the past four years, pivotal discoveries have deepened the understanding of the relationship between genetic factors and SARS-CoV-2 infection. Numerous genes associated with severe COVID-19 suggest a potential genetic predisposition, which may help explain why some individuals develop more serious illnesses. Emerging evidence highlights the role of genes involved in pulmonary immunity, such as Forkhead box Protein P4 (FOXP4), whose increased expression in lung tissue has been linked to more severe disease. Other genes - Transmembrane Protease Serine-2 (TMPRSS2), Leucine Zipper Transcription Factor Like-1 (LZTFL1), Solute Carrier family 6 member 20 (SLC6A20), Tyrosine Kinase-2 (TYK2), Angiotensin-Converting Enzyme (ACE), and FYVE and Coiled-Coil Domain-Containing-1 (FYCO1) - have also been implicated in COVID-19 severity. In contrast, certain genetic variants - such as the T-allele of rs12329760 in the TMPRSS2 gene and rs35705950-T in the Mucin-5B (MUC5B) gene - may confer protection against severe disease. Overall, the evidence suggests that genetic factors can influence both susceptibility to and protection from severe COVID-19, although these associations are likely shaped by complex interactions with environmental, behavioral, and other biological factors. This review summarizes current knowledge on genetic determinants linked to COVID-19 outcomes.},
}

@article {pmid40540167,
year = {2025},
author = {Lang, SM and Schiffl, H},
title = {Long-term renal consequences of COVID-19. Emerging evidence and unanswered questions.},
journal = {International urology and nephrology},
volume = {},
number = {},
pages = {},
pmid = {40540167},
issn = {1573-2584},
abstract = {PURPOSE: COVID-19 infection is associated with a high burden of acute or acute on chronic kidney injury (AKI), particularly in critically ill patients. Given the large numbers of COVID-19 survivors, characterization of long-term adverse kidney effects of COVID-19 have important implications for post-COVID-19 care.

METHODS: This narrative review provides a summary of epidemiologic evidence for post-COVID kidney disorders.

RESULTS: Precise post-COVID renal data are scarce. The true burden of long-COVID chronic kidney disease (CKD) remains unknown owing to under-recognition, under-diagnosis, clinical heterogeneity of patients, incomplete follow-up, and temporal trends in critical COVID-19 disease across waves of the pandemic. Collectively, the few well-designed studies assessing the impact of long-COVID on kidney health found that the overwhelming majority of patients with normal renal function at admission and without AKI during acute COVID-19 disease preserved kidney function. Post-infection kidney function trajectories of patients who experience a loss of renal function vary. Kidney function may decline gradually even in non-hospitalized patients, hospitalized patients may experience a rapid loss of kidney function 6-12 months after COVID-19 diagnosis or hospital discharge resulting from AKI during the acute phase of the disease. End-stage renal disease may occur after non-recovery from AKI and rapid progression of pre-existing CKD. Multiple mechanisms may trigger post-COVID CKD including maladaptive repair after AKI, or progression of renal lesions of systemic co-morbidities, persistence of the virus and dysregulation of inflammatory cytokines.

CONCLUSIONS: The COVID-19 pandemic has significantly impacted and may continue to have an impact on kidney health. Patients at risk have a higher propensity to develop critical COVID-19 disease. Post-COVID-19 care must pay close attention to renal function in patients discharged from hospital.},
}

@article {pmid40534826,
year = {2025},
author = {Souissi, A and Prieto-González, P and Ben Saad, H},
title = {Widespread pain syndrome in long COVID-19: melatonin as an adjuvant treatment.},
journal = {Frontiers in pain research (Lausanne, Switzerland)},
volume = {6},
number = {},
pages = {1609095},
pmid = {40534826},
issn = {2673-561X},
abstract = {Long coronavirus disease 2019 (LC19) represents a complex global health challenge. Survivors frequently report persistent problems like widespread pain syndrome (WPS), cognitive dysfunction, cardiovascular complications, and sleep disturbances. These health problems, which are worsened by oxidative stress and inflammaging, open the prospect of treatment strategies targeting these mechanisms. Melatonin is a potential option for treating LC19 problems because of its anti-inflammatory, antioxidant, and pain-modulating properties. Melatonin targets shared pathological pathways, offering a promising approach to reducing inflammation, oxidative stress, and neuroendocrine dysfunction. The present mini-review explores the therapeutic potential of melatonin in the treatment of LC19, focusing on its effects on WPS and inflammation.},
}

@article {pmid40531392,
year = {2025},
author = {da Silva, MD and da Silva, TS and Mendes, CG and Valbão, MCM and Badu-Tawiah, AK and Laurindo, LF and Barbalho, SM and Direito, R and Miglino, MA},
title = {Advances in Understanding Long COVID: Pathophysiological Mechanisms and the Role of Omics Technologies in Biomarker Identification.},
journal = {Molecular diagnosis & therapy},
volume = {},
number = {},
pages = {},
pmid = {40531392},
issn = {1179-2000},
support = {200177/2022-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {Long coronavirus disease (COVID) is a multisystem condition that affects a significant proportion of individuals following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with persistent symptoms ranging from fatigue and cognitive dysfunction to cardiovascular disorders. It is estimated that 30-60% of infected individuals experience symptoms lasting more than 12 weeks. Despite advances in understanding acute infection, the pathophysiological mechanisms underlying long COVID remain unclear. Current hypotheses suggest that viral persistence, immune dysfunction, and metabolic alterations play central roles. Omics approaches, including metabolomics, proteomics, and lipidomics, have played a crucial role in investigating molecular changes, identifying biomarkers, and refining therapeutic strategies. This review discusses recent advances in understanding long COVID, addressing its mechanisms, risk factors, the impact of viral variants, and the role of vaccination, with an emphasis on the importance of omics technologies in elucidating this condition.},
}

@article {pmid40529374,
year = {2025},
author = {Trautmann, A},
title = {Core features and inherent diversity of post-acute infection syndromes.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1509131},
pmid = {40529374},
issn = {1664-3224},
mesh = {Humans ; Post-Acute COVID-19 Syndrome ; Animals ; Fatigue/etiology ; *Infections/immunology/complications ; Critical Illness ; },
abstract = {Post-acute infection syndromes (PAIS), i.e., long-lasting pathologies subsequent to infections that do not properly resolve, have both a common core and a broad diversity of manifestations. PAIS include a group of core symptoms (pathological fatigue, cognitive problems, sleep disorders and pain) accompanied by a large set of diverse symptoms. Core and diverse additional symptoms, which can persist for years, exhibiting periods of relapses and remissions, usually start suddenly after an apparently common infection. PAIS display highly variable clinical features depending on the nature of the initial pathogen, and to an even larger extent, on the diversity of preexisting individual terrains in which PAIS are rooted. In a first part, I discuss biological issues related to the persistence of microbial antigens, dysregulated immune responses, reactivation of latent viruses, different potential self-sustained inflammatory loops, mitochondrial dysfunction, metabolic disorders in the tryptophan- kynurenin pathway (TKP) with impact on serotonin, and consequences of a dysfunctional bidirectional microbiota-gut-brain axis. The second part deals with the nervous system dependence of PAIS. I rely on the concept of interoception, the process by which the brain senses, integrates and interprets signals originating from within the body, and sends feebacks aimed at maintaining homeostasis. Interoception is central for understanding the origin of fatigue, dysautonomia, dysfunctioning of the hypothalamus-pituitary-adrenal (HPA) axis, and its relation with stress, inflammation or depression. I propose that all individual predispositions leading to self-sustained vicious circles constitute building blocks that can self-assemble in many possible ways, to give rise to both core and diverse features of PAIS. A useful discrimination between different PAIS subtypes should be obtained with a composite profiling including biomarkers, questionnaires and functional tests so as to take into account PAIS multidimensionality.},
}

Humans
Post-Acute COVID-19 Syndrome
Animals
Fatigue/etiology
*Infections/immunology/complications
Critical Illness

@article {pmid40514644,
year = {2025},
author = {Elboraay, T and Ebada, MA and Elsayed, M and Aboeldahab, HA and Salamah, HM and Rageh, O and Elmallahy, M and AboElfarh, HE and Mansour, LS and Nabil, Y and Eltawab, AKA and Atwan, H and Alkanj, S},
title = {Long-term neurological and cognitive impact of COVID-19: a systematic review and meta-analysis in over 4 million patients.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {250},
pmid = {40514644},
issn = {1471-2377},
mesh = {Humans ; *COVID-19/complications/psychology/epidemiology ; *Nervous System Diseases/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology/etiology ; Prevalence ; Fatigue/epidemiology ; },
abstract = {BACKGROUND: Neuropsychiatric symptoms emerged early in the COVID-19 pandemic as a key feature of the virus, with research confirming a range of neuropsychiatric manifestations linked to acute SARS-CoV-2 infection. However, the persistence of neurological symptoms in the post-acute and chronic phases remains unclear. This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning.

METHODS: A comprehensive literature search was conducted across five electronic databases: PubMed, Scopus, Web of Science, EBSCO, and CENTRAL, up to March 22, 2024. Studies evaluating the prevalence of long-term neurological symptoms in COVID-19 survivors with at least six months of follow-up were included. Pooled prevalence estimates, subgroup analyses, and meta-regression were performed, and publication bias was assessed.

RESULTS: The prevalence rates for the different symptoms were as follows: fatigue 43.3% (95% CI [36.1-50.9%]), memory disorders 27.8% (95% CI [20.1-37.1%]), cognitive impairment 27.1% (95% CI [20.4-34.9%]), sleep disorders 24.4% (95% CI [18.1-32.1%]), concentration impairment 23.8% (95% CI [17.2-31.9%]), headache 20.3% (95% CI [15-26.9%]), dizziness 16% (95% CI [9.5-25.7%]), stress 15.9% (95% CI [10.2-24%]), depression 14.0% (95% CI [10.1-19.2%]), anxiety 13.2% (95% CI [9.6-17.9%]), and migraine 13% (95% CI [2.2-49.8%]). Significant heterogeneity was observed across all symptoms. Meta-regression analysis showed higher stress, fatigue, and headache in females, and increased stress and concentration impairment with higher BMI.

CONCLUSIONS: Neurological symptoms are common and persistent in COVID-19 survivors. This meta-analysis highlights the significant burden these symptoms place on individuals, emphasizing the need for well-resourced multidisciplinary healthcare services to support post-COVID recovery.

REGISTRATION AND PROTOCOL: This meta-analysis was registered in PROSPERO with registration number CRD42024576237.},
}

Humans
*COVID-19/complications/psychology/epidemiology
*Nervous System Diseases/epidemiology/etiology
*Cognitive Dysfunction/epidemiology/etiology
Prevalence
Fatigue/epidemiology

@article {pmid40512228,
year = {2025},
author = {Goldenberg, DL},
title = {The pivotal role of central sensitization in long COVID, fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Expert review of neurotherapeutics},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/14737175.2025.2516097},
pmid = {40512228},
issn = {1744-8360},
abstract = {INTRODUCTION: Long COVID is a condition characterized by persistent unexplained symptoms following COVID-19 infection. These symptoms are not related to another disease or organ damage and are similar to those in fibromyalgia and myslgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

AREAS COVERED: The similar clinical and pathophysiological features and management of long COVID, fibromyalgia and ME/CFS are explored from the unifying framework of central sensitivity syndromes. The article is based on a literature search utilizing PubMed for content published between 2021 and 1 May 2025, using search terms: long COVID, long COVID syndrome, post-COVID-19, post-acute SARS-CoV-2, fibromyalgia, ME/CFS, post-exertional malaise and central sensitization.

EXPERT OPINION: Once long COVID is redefined to exclude patients with well-defined organ disease, it fits best as a model of central sensitization. Long COVID is a single syndrome, rather than many distinct diseases. Optimal management of long COVID and similar central sensitivity syndromes should include personalized care with a primary care led-multidisciplinary team.},
}

@article {pmid40507911,
year = {2025},
author = {Popa, E and Popa, AE and Poroch, M and Poroch, V and Ungureanu, MI and Slanina, AM and Bacusca, A and Coman, EA},
title = {The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review.},
journal = {International journal of molecular sciences},
volume = {26},
number = {11},
pages = {},
doi = {10.3390/ijms26115102},
pmid = {40507911},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/metabolism ; *Cognitive Dysfunction/etiology/metabolism/virology ; SARS-CoV-2 ; Biomarkers/metabolism ; Blood-Brain Barrier/metabolism ; },
abstract = {Cognitive dysfunction represents one of the most persistent and disabling features of Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on the pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include persistent neuroinflammation, blood-brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, and neuroendocrine imbalance. Microglial activation and cytokine release (e.g., IL-6, TNF-α) promote synaptic dysfunction and neuronal injury, while activation of inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis and BBB leakage, facilitate the infiltration of peripheral immune cells and neurotoxic mediators. Hypothalamic-pituitary-adrenal axis dysfunction and reduced vagal tone further exacerbate systemic inflammation and autonomic imbalance. Biomarkers such as GFAP, NFL, IL-6, and S100B have been associated with both neuroinflammation and cognitive symptoms. Notably, transcriptomic signatures in Long COVID overlap with those observed in Alzheimer's disease, highlighting shared pathways involving tau dysregulation, oxidative stress, and glial reactivity. Understanding these mechanisms is critical for identifying at-risk individuals and developing targeted therapeutic strategies. This review underscores the need for longitudinal research and integrative biomarker analysis to elucidate the molecular trajectory of cognitive impairment in Long COVID.},
}

Humans
*COVID-19/complications/metabolism
*Cognitive Dysfunction/etiology/metabolism/virology
SARS-CoV-2
Biomarkers/metabolism
Blood-Brain Barrier/metabolism

@article {pmid40507071,
year = {2025},
author = {Bigman, G and Rusu, ME and Shelawala, N and Sorkin, JD and Beamer, BA and Ryan, AS},
title = {A Comprehensive Scoping Review on Diet and Nutrition in Relation to Long COVID-19 Symptoms and Recovery.},
journal = {Nutrients},
volume = {17},
number = {11},
pages = {},
doi = {10.3390/nu17111802},
pmid = {40507071},
issn = {2072-6643},
mesh = {Humans ; *COVID-19/complications/physiopathology/diet therapy ; *Nutritional Status ; *Diet ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Adult ; },
abstract = {Background/Objectives: Long COVID-19 is characterized by persistent symptoms lasting three months or more following SARS-CoV-2 infection. Nutrition has emerged as a modifiable factor influencing recovery trajectories and symptom burden; however, existing evidence remains fragmented across diverse study designs and populations. This scoping review synthesized global evidence on the role of diet and nutrition in managing long COVID-19 symptoms and supporting recovery. Methods: Following PRISMA-ScR and Joanna Briggs Institute guidelines for scoping reviews, we searched major biomedical databases for studies published between 2020 and 2025. Eligible studies examined dietary intake, nutritional status, or nutrition-related interventions in adults with long COVID-19. Results: After duplicates were removed, 1808 records were screened, resulting in 50 studies that met the inclusion criteria-27 intervention studies and 23 observational studies. Nutritional exposures included micronutrients (e.g., vitamins D, K2), amino acids (e.g., L-arginine), multinutrient formulations, microbiota-targeted therapies (e.g., probiotics, synbiotics), nutritional status, diet quality, and whole-diet patterns (e.g., the Mediterranean diet). Approximately 76% of studies reported improvements in long COVID-19-related symptoms such as fatigue, mood disturbances, physical function, and markers of inflammation. Conclusions: Diet and nutrition may support long COVID-19 recovery by targeting inflammation and the gut microbiome to alleviate symptoms and improve functional outcomes. Well-powered trials of whole-diet approaches, combined with targeted supplementation, are needed to confirm their potential as scalable, accessible tools for post-COVID-19 recovery and management.},
}

Humans
*COVID-19/complications/physiopathology/diet therapy
*Nutritional Status
*Diet
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Adult

@article {pmid40393269,
year = {2025},
author = {Struhal, W and Almamoori, D},
title = {A review of the sequelae of post Covid-19 with neurological implications (post-viral syndrome).},
journal = {Journal of the neurological sciences},
volume = {474},
number = {},
pages = {123532},
doi = {10.1016/j.jns.2025.123532},
pmid = {40393269},
issn = {1878-5883},
mesh = {Humans ; *COVID-19/complications ; *Nervous System Diseases/etiology/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Post Covid-19 conditions represent a medical challenge; a unified definition is not achieved after 5 years of the Pandemic. The incidence of Post Covid-19 conditions varies, nevertheless the neurological complications represent an important aspect in the spectrums of fields involved. The current perception is that varied manifestations and long-term complications of COVID-19 reflect underlying pathophysiological processes, including inflammatory, immune-mediated, and vascular mechanisms. These mechanisms underscore the complexity of COVID-19's impact including the nervous system and its potential for lasting effects. A number of symptoms are extremely severe and may also need neurologic attention including fatigue, cognitive disturbances, autonomic symptoms, headache, and sleep disorders. Post Covid-19 conditions are often of chronic nature. Management as in other chronic conditions should rely on the conventional diagnostic measures and management of symptoms irrespective of the temporal relation to the viral infection. To date Post Covid-19 conditions is only accepted as an additional or explanatory diagnosis.},
}

Humans
*COVID-19/complications
*Nervous System Diseases/etiology/epidemiology
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid40496528,
year = {2024},
author = {Akbari, B and Wang, JM and Baghaei-Yazdi, N and Lahooti, H and Sherman, JH},
title = {Systems Thinking, Causal Loop Diagram, and Systems Dynamic in Public Health Challenges: Navigating Long COVID Syndrome and Sense of Smell in LGBTQIA+ Communities.},
journal = {Public health challenges},
volume = {3},
number = {3},
pages = {e70004},
pmid = {40496528},
issn = {2769-2450},
abstract = {BACKGROUND: The coronavirus pandemic has profoundly affected global health, economic stability, and environmental sustainability. Despite these challenges, significant gaps in data remain, particularly in effectively assessing and engaging diverse communities such as color, LGBTQIA+ individuals, and low-income groups. This shortage of comprehensive research limits our capacity to undertake sensitive studies, specifically in dealing with the complexities of long COVID, which some individuals continue to suffer from after their initial recovery.

OBJECTIVE: This review delves into the ongoing repercussions of long-term COVID-19, a postinfectious syndrome marked by neurological symptoms such as cognitive deficits and sensory impairments, which may last well beyond the acute phase of the illness. These symptoms frequently overlap with mental health issues (e.g., anxiety and depression), which can aggravate the socioeconomic challenges faced by vulnerable populations, especially within the LGBTQA+ communities.

METHODS: To tackle these complex interactions, we have introduced a novel public health framework: model-based systems thinking (MBST), which incorporates System Dynamics and causal loop diagrams (CLD).

RESULTS AND DISCUSSION: The articles were selected on the basis of their discussion of COVID-19-associated anosmia, exploration of olfactory dysfunction alongside neurocognitive disorders, and the challenges experienced in LGBQA+ communities. This approach offers a robust framework for dissecting the intricate ties between socioeconomic factors, health outcomes, and the extended recovery trajectories associated with long-term COVID-19, with a particular focus on olfactory dysfunction. We also explore strategies to make our models more accessible to healthcare providers and the LGBTQA+ communities, encouraging its broader adoption.

CONCLUSION: Long COVID's impact on public health and marginalized communities highlights the urgent need for adopting systems thinking models. Additionally, this article calls for a concerted effort from all experts to foster multidisciplinary, team-based research and implement effective support measures for COVID-19 survivors across all communities, mainly focusing on the scientific, social, and behavioral challenges LGBTQIA+ and low-income individuals face.},
}

@article {pmid40492581,
year = {2025},
author = {Vlaming-van Eijk, LE and Tang, G and Bourgonje, AR and den Dunnen, WF and Hillebrands, JL and van Goor, H},
title = {Post-COVID-19 condition: clinical phenotypes, pathophysiological mechanisms, pathology, and management strategies.},
journal = {The Journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1002/path.6443},
pmid = {40492581},
issn = {1096-9896},
abstract = {Post-COVID-19 condition (PCC), also known as long COVID, is a complex multiple organ system condition that can develop and persist for months after acute COVID-19. PCC encompasses a wide range of symptoms, resulting in heterogeneous clinical manifestations. These manifestations likely arise from diverse underlying pathophysiological mechanisms, which, in turn, are influenced by risk factors such as age, sex, and comorbidities. To this end, characterising clinical phenotypes of PCC is essential for deepening our understanding of its (potentially) distinct pathophysiological mechanisms and for advancing diagnostic and patient-tailored management strategies. PCC is thought to result from a complex interaction of various pathophysiological mechanisms, leading to functional and structural pathological alterations across multiple organ systems. Investigating these alterations is critical to improving our currently incomplete understanding of PCC's complex pathophysiology. This review provides an overview of the main clinical phenotypes of PCC, characterises these phenotypes by examining symptoms and signs, as well as the associated risk factors. The main hypothesised pathophysiological mechanisms are discussed by outlining the current knowledge on PCC pathology, focussing on the most commonly affected organ systems. Current PCC management includes supportive care such as physiotherapy and the repurposing of existing drugs primarily targeting persistence of SARS-CoV-2 (e.g. antivirals, monoclonal antibodies) and immune dysfunction (e.g. antiinflammatory drugs, immunomodulators). To date, prevention of SARS-CoV-2 infection remains critical, which can be achieved through effective public health measures and vaccination strategies. Finally, this review highlights current knowledge gaps and proposes future research directions to advance the understanding and treatment of PCC. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.},
}

@article {pmid40481619,
year = {2025},
author = {Linton, J and Carmichael, J and Newlands, F and Puri, A and Fox-Smith, L and Pinto Pereira, SM and Coughtrey, A and Shafran, R and Stephenson, T},
title = {Pre-Pandemic Prevalence of Post COVID-19 Condition Symptoms in Adolescents.},
journal = {Acta paediatrica (Oslo, Norway : 1992)},
volume = {},
number = {},
pages = {},
doi = {10.1111/apa.70123},
pmid = {40481619},
issn = {1651-2227},
support = {COV-LT-0022//UK Research and Innovation/ ; 183885//Beryl Alexander Charity PhD Studentship/ ; MR/Y009398/1//UK Medical Research Council Senior Non-clinical Fellowship/ ; //NIHR Great Ormond Street Hospital Biomedical Research Centre/ ; },
abstract = {AIM: The emergence of post COVID-19 condition (PCC) within adolescents has been characterised by a wide range of symptoms, raising concerns for young people's health and quality of life. However, many symptoms are non-specific and there is considerable variation in symptom reporting. It is essential to understand how rates of these symptoms compare to the pre-pandemic health of adolescents.

METHODS: A systematic search of academic literature and websites, using traditional and automated search systems, was undertaken to identify symptoms described in adolescents aged 10-19 years in the 30 years up to and including 2019. Studies were reviewed and symptom prevalence data extracted.

RESULTS: Twenty-five sources (n = 483 097 participants) met the inclusion criteria, including longitudinal and cross-sectional study designs. The description and prevalence of symptoms varied widely, but there was a high pre-pandemic median prevalence of cough (13.6%), headache (30.0%), and fatigue (20.5%). These high prevalences highlight a gap in understanding of pre-pandemic adolescent health and the need for comprehensive, serial symptom profiling.

CONCLUSION: These findings provide a baseline of adolescent symptomatology prior to the emergence of PCC and provide important context for interpreting ongoing COVID symptoms. Data on PCC in adolescents should consider pre-pandemic symptom prevalence.},
}

@article {pmid40476637,
year = {2025},
author = {Rahmati, M and Udeh, R and Kang, J and Dolja-Gore, X and McEvoy, M and Kazemi, A and Soysal, P and Smith, L and Kenna, T and Fond, G and Boussat, B and Nguyen, DC and Do, H and Tran, BX and Veronese, N and Yon, DK and Boyer, L},
title = {Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of Symptoms 3 Years Post-SARS-CoV-2 Infection.},
journal = {Journal of medical virology},
volume = {97},
number = {6},
pages = {e70429},
doi = {10.1002/jmv.70429},
pmid = {40476637},
issn = {1096-9071},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Fatigue/epidemiology ; Dyspnea/epidemiology ; SARS-CoV-2 ; Prevalence ; Sleep Wake Disorders/epidemiology ; Post-Acute COVID-19 Syndrome ; Survivors ; },
abstract = {The symptoms of long COVID are well-documented. However, the long-term effects beyond 2 years remain poorly understood due to a lack of data. This systematic review and meta-analysis examined the prevalence of persistent symptoms in COVID-19 survivors 3 years following initial SARS-CoV-2 infection. PubMed, MEDLINE (Ovid), CENTRAL, Web of Science, Scopus, and Embase were searched from inception of the databases up to July 20, 2024, by two independent researchers for articles reporting on the prevalence of persistent symptoms 3 years' post-infection of people who survived COVID-19 infection. We employed a random-effect model for the pooled analysis, and the meta-analytical effect size was prevalence for the applicable end-points, I[2] statistics, and quality assessment of included studies using the Newcastle-Ottawa Scale. Eleven articles were included after the literature search yielded 223 potentially relevant articles. We found that among patients with long COVID, fatigue, sleep disturbances, and dyspnea were the most common symptoms. Pooled analysis showed that the proportion of individuals experiencing at least one persistent symptom 3 years post-COVID-19 is 20% (95% confidence interval [CI]: 8-43). The prevalence of persistent symptoms was dyspnea (12%; 95% CI: 10-15), fatigue (11%; 95% CI: 6-20), insomnia (11%; 95% CI: 2-37), loss of smell (7%; 95% CI: 5-8), loss of taste (7%; 95% CI: 3-16), and anxiety (6%; 95% CI: 1-32). Prevalence of other findings include impaired diffusion capacity (42%; 95% CI: 34-50) and impaired forced expiratory volume in 1 s (10%; 95% CI: 8-12). Our findings confirm the persistence of unresolved symptoms 3 years post-COVID-19 infection, with implications for future research, healthcare policy, and patient care.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology
Fatigue/epidemiology
Dyspnea/epidemiology
SARS-CoV-2
Prevalence
Sleep Wake Disorders/epidemiology
Post-Acute COVID-19 Syndrome
Survivors

@article {pmid40474772,
year = {2025},
author = {Gupta, G and Buonsenso, D and Wood, J and Mohandas, S and Warburton, D},
title = {Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.},
journal = {Comprehensive Physiology},
volume = {15},
number = {3},
pages = {e70019},
doi = {10.1002/cph4.70019},
pmid = {40474772},
issn = {2040-4603},
mesh = {Humans ; *COVID-19/immunology/complications/virology/physiopathology ; *SARS-CoV-2/physiology ; *Multiple Organ Failure/immunology/virology/etiology ; Post-Acute COVID-19 Syndrome ; Animals ; },
abstract = {Long Covid is a post-viral syndrome characterized by persistent symptoms targeting multiple organ systems after initial SARS-CoV-2 infection. Current literature suggests that the mechanisms causing Long Covid involve viral persistence, immune dysregulation, systemic inflammation, endothelial dysfunction, and metabolic disturbances. By forming reservoirs in the tissues of various organs, SARS-CoV-2 may evade immunological clearances while triggering immune responses and contributing to chronic symptoms through cytokine imbalances, T-cell exhaustion, and systemic inflammation. These symptoms parallel other post-viral syndromes such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), suggesting similar mechanisms of pathology. The coronavirus has also been linked to neuroinflammation and endothelial dysfunction causing cognitive symptoms and cardiovascular complications. Furthermore, its ability to lower energy production links it to post-exertion malaise (PEM) and muscle pain. These symptoms may result from iron dysregulation and persistent oxidative stress due to Covid-impaired mitochondrial function. This review synthesizes current data on the mechanisms that drive Long Covid pathogenesis and explores potential therapeutic strategies to mitigate viral persistence, immune dysfunction, and metabolic disturbances. It is critical to understand these interactions to develop targeted interventions that address the long-term sequelae of SARS-CoV-2 infection and improve patient outcomes.},
}

Humans
*COVID-19/immunology/complications/virology/physiopathology
*SARS-CoV-2/physiology
*Multiple Organ Failure/immunology/virology/etiology
Post-Acute COVID-19 Syndrome
Animals

@article {pmid40479330,
year = {2022},
author = {Tuta Quintero, E and Mosquera Pongutá, AC and Barroso da Silva, EA and Olivella, J and Silvera, AA and Aragón, C and Vásquez, L and Collazos, E and Olivares Vigles, K and Martínez, K and León Machicado, M and Díaz Pérez, YN and Pimentel, J},
title = {[SARS-CoV-2 and post-COVID-19 syndrome in paediatric rheumatology: A scoping review].},
journal = {Revista colombiana de reumatologia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.rcreu.2022.10.003},
pmid = {40479330},
issn = {2027-9000},
abstract = {INTRODUCTION: An increasing number of musculoskeletal clinical manifestations, the onset of diseases and rheumatological manifestations have been seen in the paediatric population surviving COVID-19, however, the medical literature on the subject is limited.

OBJECTIVE: To explore the available evidence on musculoskeletal symptoms and autoimmune diseases in the paediatric population with post-COVID syndrome.

METHODOLOGY: Scoping systematic review in PubMed and Scopus through search strategies. Observational and experimental studies are included in populations under 21 years of age with and without autoimmune diseases, without time limit in English and Spanish.

RESULTS: The 28 documents included: case reports (n = 6), cross-sectional studies (n = 5), prospective cohort studies (n = 5), retrospective cohort (n = 6), case series (n = 6), ambidirectional section (n = 1), randomized controlled trial (n = 1), and longitudinal section study (n = 1). The total study population was 56,738 patients. The most frequent symptoms presented in long COVID-19 are myalgias and arthralgias. The evidence showing a relationship between SARS-CoV-2 infection in the development of musculoskeletal symptoms and autoimmune diseases in the convalescent period is limited.

CONCLUSIONS: Myalgias and arthralgias are the most frequent symptoms in long COVID. patients with SARS-CoV-2 infection and a history of rheumatic disease who are undergoing immunomodulatory treatment do not have a dangerous risk of developing severe presentations and/or complications of the disease.},
}

@article {pmid40478033,
year = {2022},
author = {Barroso, E and Tuta-Quintero, E and Olivella, J and Aragón, C and Vásquez, L and Acosta, L and Pinzón, O and Pantoja, CA and Collazos, E and Ascanio, YP and Morales, VDCDR and Kuan, JC and Velásquez, LA and Díaz, YN and Pimentel, J},
title = {[Guillain Barré syndrome in the paediatric population. Consequence of active infection or long Covid?].},
journal = {Revista colombiana de reumatologia},
volume = {29},
number = {4},
pages = {335-346},
pmid = {40478033},
issn = {2027-9000},
abstract = {BACKGROUND: Guillain-Barré syndrome is a polyradiculoneuropathy that has been associated with infectious diseases as triggers. There is currently little medical evidence exploring the relationship between the development of Guillain-Barré syndrome caused by SARS-CoV-2 infection and long Covid.

OBJECTIVE: To synthesize the medical evidence that describes the relationship between post Covid syndrome and Guillain-Barré syndrome in the paediatric population.

METHODOLOGY: A scoping review was developed using Scopus and PubMed databases, including analytical and/or descriptive experimental and observational studies.

RESULTS: The main clinical manifestations presented by paediatric patients were distal and ascending weakness in the lower limbs and myalgia. The diagnostic approach was based on clinical findings, imaging findings on spinal magnetic resonance and electromyography. The therapeutic strategy is based on the use of intravenous human immunoglobulins.

CONCLUSION: Guillain-Barré syndrome is a frequent disease in the paediatric population with active SARS-CoV-2 infection or in survivors, however, it is necessary to encourage further clinical studies that increase the medical literature that describes this association.},
}

@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