@article {pmid41161981,
year = {2025},
author = {Vishnu, P and Aboulafia, DM},
title = {Hemostatic Disorders Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection, COVID-19 Vaccination, and Long-COVID Syndrome: Current Evidence and Controversies in Clinical Practice.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {643-655},
doi = {10.1016/j.cll.2025.07.008},
pmid = {41161981},
issn = {1557-9832},
mesh = {Humans ; *COVID-19/complications/prevention & control ; *COVID-19 Vaccines/adverse effects ; *Hemostatic Disorders/etiology ; SARS-CoV-2 ; *Vaccination/adverse effects ; },
abstract = {The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented profound global health challenges. Beyond acute illness, a substantial proportion of individuals experience persistent symptoms including fatigue, brain fog, and post-exertional malaise, collectively known as Long-COVID. Among the complications associated with SARS-CoV-2 infection and vaccination, hemostatic disorders ranging from mild platelet dysfunction to severe thromboembolic events, and rare but serious coagulation-related adverse effects, such as vaccine-induced immune thrombotic thrombocytopenia, have emerged as a significant concern. Herein we provide an overview of current information and controversies surrounding hemostatic complications in SARS-CoV-2 infection and COVID-19 vaccination.},
}

Humans
*COVID-19/complications/prevention & control
*COVID-19 Vaccines/adverse effects
*Hemostatic Disorders/etiology
SARS-CoV-2
*Vaccination/adverse effects

@article {pmid41160239,
year = {2025},
author = {Krassnig, K and Bauer, R and Glasl, S and Haubenberger, P and Evanzin, HJ and Schneider, K and Margotti, D},
title = {[Herbal treatment options for post-viral symptoms and long COVID].},
journal = {Wiener medizinische Wochenschrift (1946)},
volume = {},
number = {},
pages = {},
pmid = {41160239},
issn = {1563-258X},
abstract = {BACKGROUND: Long COVID and post-viral symptom complexes have become a significant focus in medical practice. There is an urgent need to provide evidence-based treatment options to those patients. The aim of the literature review was to summarize herbal medicinal products as a treatment option for post-viral conditions, particularly long COVID.

METHODS: A working group of the Austrian Society for Phytotherapy conducted a narrative review between 2022 and 2024, based on external literature from the PubMed, PubPharm and Scopus databases and clinical experience from practice. The review identified the most relevant medicinal plants and their preparations for the most common symptom complexes of long COVID.

RESULTS: A total of 98 publications and 24 monographs were included in the literature review. The symptom complexes (+ relevant phytopharmaceuticals) include neurological complaints, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (Ginseng radix, Panax quinquefolii radix, Eleutherocci radix, Rhodiolae rhizoma et radix, Schisandrae fructus), nootropics (Ginkgo folium, Lavandulae flos), irritations of the respiratory tract (Liquiritiae radix, Nigellae semen, Eucalypti folium), gastrointestinal complaints (Gentianae radix, Centauri herba, Artemisii herba, Galangae rhizoma, Zingiberis rhizoma, Boswellia serrata, Curcuma longae rhizoma), circulatory weakness (Crataegi folium cum flore, Rosmarini folium, Salviae officinalis folium) and loss of smell (Rosae flos, Citri pericarpium, Caryophylli flos, Eucalypti folium). External evidence and clinical experience in medical practice show that many important symptoms of post-viral conditions can be successfully treated with herbal preparations.

CONCLUSION: Phytopharmaceuticals can provide evidence-based support for the therapeutic portfolio for viral diseases and their consequences in current and future viral epidemics.},
}

@article {pmid41158347,
year = {2025},
author = {Xie, K and Zhang, P and Li, Y and Xia, L},
title = {The post-COVID-19 pulmonary sequelae: manifestations, mechanisms and treatment strategies.},
journal = {Journal of thoracic disease},
volume = {17},
number = {9},
pages = {7414-7429},
pmid = {41158347},
issn = {2072-1439},
abstract = {Recent studies have increasingly demonstrated that coronavirus disease 2019 (COVID-19) patients may develop long-term sequelae of varying severity, collectively referred to as long COVID or post-COVID-19 condition. Pulmonary sequelae are particularly common, which significantly impair patients' quality of life. The mechanisms underlying post-COVID-19 pulmonary sequelae are complex and multifactorial, and their management is still at an exploratory stage. This review explores the manifestations, underlying mechanisms, and potential treatment approaches for post-COVID-19 pulmonary sequelae. Fatigue, dyspnea, myalgia, and sleep disturbances are the most commonly reported symptoms following COVID-19 infection, while anxiety and depression are also prevalent. Respiratory symptoms include dyspnoea, persistent cough, hypoxia, and reduced exercise capacity. Impaired lung diffusion capacity is the most frequently observed pulmonary function abnormality, and residual abnormalities on chest computed tomography (CT) commonly include ground-glass opacities (GGO) and fibrotic-like changes. Air trapping is also an important CT finding and has been reported to associated with impaired lung diffusion function. The potential mechanisms may include pulmonary fibrosis, chronic inflammation, immune dysregulation, coagulation abnormalities and thrombosis, and persistent viral infection. Current treatment strategies encompass vaccination, pulmonary rehabilitation, and pharmacological interventions such as antifibrotic, anti-inflammatory, and anticoagulant therapies. A comprehensive understanding of the recovery trajectory and the mechanisms underlying post-COVID-19 pulmonary sequelae is crucial for improving patient outcomes.},
}

@article {pmid41157587,
year = {2025},
author = {Heath, AM and Li, D},
title = {Symptomatology of Long COVID Associated with Inherited and Acquired Thrombophilic Conditions: A Systematic Review.},
journal = {Viruses},
volume = {17},
number = {10},
pages = {},
doi = {10.3390/v17101315},
pmid = {41157587},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/complications ; *Thrombophilia/complications ; SARS-CoV-2 ; },
abstract = {Thrombophilic conditions, conditions where blood has a tendency to form thrombi due to abnormal coagulatory processes, can affect the trajectory of diseases such as Post-Acute Sequelae of SARS-CoV-2 Infection, better known as Long COVID (LC), by worsening symptoms and complicating outlooks. As a comorbidity in pro-coagulatory diseases such as COVID-19 and LC, patients with thrombophilic conditions may experience worse symptoms than their peers, due to this elevated level of hypercoagulation. A 15-week literature review through the public PubMed database was conducted to investigate the severity, mechanisms, and symptom profiles of thrombophilic patients with LC. Papers were only included if samples included participants with pre-existing tendencies for hypercoagulable states, and confirmation of SARS-CoV-2 infection via a Polymerase Chain Reaction test. Each paper included in this review was analyzed by topic and assessed for eligibility against the Joanna Briggs Institute's Critical Appraisal tool. Each paper was also assessed for biases. Results from the 6 papers included in this review showed that LC could be predicted following COVID-19 illness by a hypercoagulable blood profile, indicating that LC may be linked to chronic hypercoagulation and inflammation post-infection. Additionally, symptoms linked to microthrombi formation, such as hair loss, arrhythmia, and dizziness, were exhibited more frequently in patients with thrombophilia and/or thrombophilic conditions, indicating that those with thrombophilic conditions may exhibit unique LC symptom profiles compared to healthy controls. This paper's research is preliminary and thus is limited in the strength of its findings; However, further research into LC and its interactions with co-morbidities like thrombophilic conditions would aid in the development of better treatment plans for patients, such as the usage of anticoagulants or screening for hypercoagulable blood profiles post-COVID-19 to assess patient risk.},
}

Humans
*COVID-19/complications
*Thrombophilia/complications
SARS-CoV-2

@article {pmid41157582,
year = {2025},
author = {Prakash, S and Karan, S and Lekbach, Y and Tifrea, DF and Figueroa, CJ and Ulmer, JB and Young, JF and Glenn, G and Gil, D and Jones, TM and Redfield, RR and BenMohamed, L},
title = {Insights into Persistent SARS-CoV-2 Reservoirs in Chronic Long COVID.},
journal = {Viruses},
volume = {17},
number = {10},
pages = {},
doi = {10.3390/v17101310},
pmid = {41157582},
issn = {1999-4915},
support = {AI158060//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *COVID-19/virology/immunology/complications ; *SARS-CoV-2/physiology/genetics ; Animals ; Chronic Disease ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Disease Reservoirs/virology ; *Persistent Infection/virology ; },
abstract = {Long COVID (LC), also known as post-acute sequelae of COVID-19 infection (PASC), is a heterogeneous and debilitating chronic disease that currently affects 10 to 20 million people in the U.S. and over 420 million people globally. With no approved treatments, the long-term global health and economic impact of chronic LC remains high and growing. LC affects children, adolescents, and healthy adults and is characterized by over 200 diverse symptoms that persist for months to years after the acute COVID-19 infection is resolved. These symptoms target twelve major organ systems, causing dyspnea, vascular damage, cognitive impairments ("brain fog"), physical and mental fatigue, anxiety, and depression. This heterogeneity of LC symptoms, along with the lack of specific biomarkers and diagnostic tests, presents a significant challenge to the development of LC treatments. While several biological abnormalities have emerged as potential drivers of LC, a causative factor in a large subset of patients with LC, involves reservoirs of virus and/or viral RNA (vRNA) that persist months to years in multiple organs driving chronic inflammation, respiratory, muscular, cognitive, and cardiovascular damages, and provide continuous viral antigenic stimuli that overstimulate and exhaust CD4[+] and CD8[+] T cells. In this review, we (i) shed light on persisting virus and vRNA reservoirs detected, either directly (from biopsy, blood, stool, and autopsy samples) or indirectly through virus-specific B and T cell responses, in patients with LC and their association with the chronic symptomatology of LC; (ii) explore potential mechanisms of inflammation, immune evasion, and immune overstimulation in LC; (iii) review animal models of virus reservoirs in LC; (iv) discuss potential T cell immunotherapeutic strategies to reduce or eliminate persistent virus reservoirs, which would mitigate chronic inflammation and alleviate symptom severity in patients with LC.},
}

Humans
*COVID-19/virology/immunology/complications
*SARS-CoV-2/physiology/genetics
Animals
Chronic Disease
Post-Acute COVID-19 Syndrome
RNA, Viral
Disease Reservoirs/virology
*Persistent Infection/virology

@article {pmid41157147,
year = {2025},
author = {Jach, ME and Sajnaga, E and Bumbul, M and Serefko, A and Borowicz, KK and Golczyk, H and Kieliszek, M and Wiater, A},
title = {The Role of Probiotics and Their Postbiotic Metabolites in Post-COVID-19 Syndrome.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {20},
pages = {},
doi = {10.3390/molecules30204130},
pmid = {41157147},
issn = {1420-3049},
mesh = {*Probiotics/therapeutic use/pharmacology ; Humans ; *COVID-19/complications ; Gastrointestinal Microbiome/drug effects ; SARS-CoV-2 ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; },
abstract = {Post-COVID-19 syndrome, also known as long-COVID, is characterized by a wide spectrum of persistent symptoms involving multiple body organs and systems, including fatigue, gastrointestinal disorders, and neurocognitive dysfunction. Emerging evidence suggests that gut microbiota dysbiosis and disruption of the gut-brain axis play a central role in the pathophysiology of this condition. Probiotics and their metabolites (postbiotics) have gained increasing attention as potential therapeutic agents given their immunomodulatory, anti-inflammatory, and antiviral properties. In this review, we discuss the current understanding of the antiviral mechanisms of probiotics, including reinforcement of intestinal epithelial barrier function, direct virus inhibition, receptor competition, and immune system modulation. Special emphasis is placed on short-chain fatty acids (SCFAs), lactic acid, hydrogen peroxide, and bacteriocins as key factors that contribute to these effects. SCFAs appear to be essential postbiotic compounds during post-COVID recovery. We also highlight recent clinical trials involving specific probiotic species, such as Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum, and their potential role in alleviating long-term COVID symptoms. Although the current results are promising, further research is needed to clarify the most effective strains, dosages, and mechanisms of action in post-COVID therapeutic strategies.},
}

*Probiotics/therapeutic use/pharmacology
Humans
*COVID-19/complications
Gastrointestinal Microbiome/drug effects
SARS-CoV-2
Dysbiosis
Fatty Acids, Volatile/metabolism

@article {pmid41156656,
year = {2025},
author = {Delpino, MV and Quarleri, J},
title = {Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
doi = {10.3390/pathogens14101045},
pmid = {41156656},
issn = {2076-0817},
mesh = {Humans ; *Aging/metabolism ; *HIV Infections/metabolism/therapy/pathology ; *Mitochondria/metabolism/pathology ; *COVID-19/metabolism/therapy/pathology ; DNA, Mitochondrial/genetics ; *Mitochondrial Diseases/therapy ; Oxidative Stress ; SARS-CoV-2 ; Mitophagy ; },
abstract = {We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and long COVID. Shared mechanisms-including oxidative stress, impaired mitophagy and dynamics, mtDNA damage, and metabolic reprogramming-contribute to ongoing energy failure and chronic inflammation. Recent advancements highlight new therapeutic strategies such as mitochondrial transfer, transplantation, and genome-level correction of mtDNA variants, with early preclinical and clinical studies providing proof-of-concept. This review summarizes current evidence on mitochondrial changes across aging and post-viral syndromes, examines emerging organelle-based therapies, and discusses key challenges related to safety, durability, and translation.},
}

Humans
*Aging/metabolism
*HIV Infections/metabolism/therapy/pathology
*Mitochondria/metabolism/pathology
*COVID-19/metabolism/therapy/pathology
DNA, Mitochondrial/genetics
*Mitochondrial Diseases/therapy
Oxidative Stress
SARS-CoV-2
Mitophagy

@article {pmid41155411,
year = {2025},
author = {Caliman-Sturdza, OA and Hamamah, S and Iatcu, OC and Lobiuc, A and Bosancu, A and Covasa, M},
title = {Microbiome and Long COVID-19: Current Evidence and Insights.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
doi = {10.3390/ijms262010120},
pmid = {41155411},
issn = {1422-0067},
support = {760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; 760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; },
mesh = {Humans ; *COVID-19/microbiology/complications ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Dysbiosis/microbiology ; Post-Acute COVID-19 Syndrome ; Probiotics/therapeutic use ; *Microbiota ; },
abstract = {Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut-brain and gut-lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID.},
}

Humans
*COVID-19/microbiology/complications
*Gastrointestinal Microbiome
SARS-CoV-2
Dysbiosis/microbiology
Post-Acute COVID-19 Syndrome
Probiotics/therapeutic use
*Microbiota

@article {pmid41155179,
year = {2025},
author = {Refrigeri, M and Tola, A and Mogavero, R and Pietracupa, MM and Gionta, G and Scatena, R},
title = {Mechanisms of Mitochondrial Impairment by SARS-CoV-2 Proteins: A Nexus of Pathogenesis with Significant Biochemical and Clinical Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
doi = {10.3390/ijms26209885},
pmid = {41155179},
issn = {1422-0067},
mesh = {Humans ; *Mitochondria/metabolism/virology/pathology ; *COVID-19/metabolism/virology/pathology ; *SARS-CoV-2/metabolism/pathogenicity ; Reactive Oxygen Species/metabolism ; Host-Pathogen Interactions ; Immunity, Innate ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely interacts with host cellular mechanisms, with mitochondria playing a crucial role in this process. As essential organelles that control cellular energy production, apoptosis, reactive oxygen species (ROS) metabolism, and innate immune responses, mitochondria are vital to the development of COVID-19. However, the exact molecular interactions between mitochondria and SARS-CoV-2 remain under active investigation. Gaining a comprehensive understanding of mitochondrial involvement in SARS-CoV-2 infection is therefore essential for uncovering complex disease mechanisms, identifying prognostic biomarkers, and developing effective treatments. Ultimately, exploring these virus-host interactions may provide new insights into the fundamental and complex aspects of mitochondrial physiology and pathophysiology.},
}

Humans
*Mitochondria/metabolism/virology/pathology
*COVID-19/metabolism/virology/pathology
*SARS-CoV-2/metabolism/pathogenicity
Reactive Oxygen Species/metabolism
Host-Pathogen Interactions
Immunity, Innate

@article {pmid41146789,
year = {2025},
author = {Dudek, A and Bursy, M and Szkudlarek, W and Linkiewicz, J and Fabiszewski, Z and Starosta, P},
title = {Chronic Cardiovascular Disorders Associated With COVID-19: A Literature Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93271},
pmid = {41146789},
issn = {2168-8184},
abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, is now widely recognized for causing several long-term effects known as post-COVID-19 syndrome (PCS) or long COVID (LC). This presents a growing challenge for healthcare systems worldwide. This narrative review summarizes original peer-reviewed studies indexed in PubMed and published between January 2020 and August 2025. It focuses on adult populations unless stated otherwise. We included studies that provided primary clinical or imaging data on chronic cardiovascular outcomes after confirmed SARS-CoV-2 infection. We excluded case reports, pediatric-only cohorts, and non-peer-reviewed sources. Among the various cardiovascular issues related to LC, we focused on heart fibrosis (HF), postural orthostatic tachycardia syndrome (POTS), new-onset hypertension (HT), and coagulopathy. These conditions consistently show up in the reports and are significant in terms of illness, potential long-term disability, and public health impact. Although these issues are distinct in their underlying causes, they share common mechanisms. These include ongoing inflammation of the endothelium, disruption of the renin-angiotensin-aldosterone system (RAAS), immune-related tissue damage, and an ongoing state that promotes blood clots. These processes can lead to measurable myocardial fibrosis that cardiac magnetic resonance imaging can detect, autonomic dysfunction often seen as POTS, a greater risk of developing hypertension shortly after infection, and a long-term rise in thromboembolic events due to increased clotting and resistant microclots. Current management is mostly focused on relief of symptoms and involves a team approach. It uses repurposed medications and tailored physical rehabilitation since no specific cure is available yet. Promising but still experimental methods, such as endothelial-protective agents like sulodexide and targeting inflammatory pathways, need thorough testing. There are significant gaps in our understanding of the long-term risk of hypertension, the natural progression of fibrosis, and the best treatment for POTS. This highlights urgent needs for future research. Beyond caring for individual patients, these ongoing cardiovascular problems raise important public health concerns. They include higher healthcare use, long-term disability, and economic costs. This situation requires increased clinical attention and proactive cardiovascular monitoring for those recovering from COVID-19.},
}

@article {pmid41145456,
year = {2025},
author = {Sujith, S and Gatzke, N},
title = {An overview of clinical presentation and management of long COVID.},
journal = {The Nurse practitioner},
volume = {50},
number = {11},
pages = {38-42},
doi = {10.1097/01.NPR.0000000000000374},
pmid = {41145456},
issn = {1538-8662},
mesh = {Humans ; *COVID-19/nursing/complications/therapy ; Risk Factors ; Nurse Practitioners ; SARS-CoV-2 ; },
abstract = {The COVID-19 pandemic has been the 21st century's most significant public health emergency. In addition to the acute symptoms of COVID-19, many individuals are facing long-term health issues related to the infection. The terms "long COVID," "postacute sequelae of SARS-CoV-2 infection," "postacute COVID syndrome," and "long-haul COVID-19" refer to long-term consequences of SARS-CoV-2 infection. Symptoms may persist for weeks or months, reducing quality of life. Health practitioners must stay updated and take proactive measures to manage long COVID effectively. This manuscript provides an overview of risk factors, diagnostic tools, and management strategies, which serve as a resource for understanding and managing long COVID.},
}

Humans
*COVID-19/nursing/complications/therapy
Risk Factors
Nurse Practitioners
SARS-CoV-2

@article {pmid40329717,
year = {2025},
author = {Parwani, S and Upreti, S and Mishra, CK and Tripathi, A and Chakraborty, S and Tiwari, S},
title = {Navigating the COVID-19 Treatment Landscape: Efficacy and Side-Effects of Current Therapies against SARS-CoV-2.},
journal = {Current HIV research},
volume = {23},
number = {3},
pages = {145-160},
doi = {10.2174/011570162X338375250414114957},
pmid = {40329717},
issn = {1873-4251},
mesh = {Humans ; COVID-19/immunology ; *SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use/adverse effects ; *COVID-19 Drug Treatment ; COVID-19 Vaccines/immunology ; *HIV Infections/complications/immunology/drug therapy ; Drug Repositioning ; },
abstract = {Coronavirus Disease 2019 (COVID-19), caused by the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China. Designated as an epidemic by the World Health Organization (WHO) on January 30, 2020, the virus quickly escalated to a global emergency, officially declared a pandemic in March 2020. With over 6 million recorded deaths and more than 200 identified symptoms in diverse individuals, the impact of COVID-19 is substantial. COVID-19 poses a greater risk to individuals with advanced HIV, while those with well-managed HIV are not at increased risk. Although COVID-19 vaccines are generally effective for people with HIV, some may experience reduced vaccine effectiveness and breakthrough infections due to suboptimal immune responses. Long COVID, affecting at least 65 million individuals, adds a layer of complexity. The virus's rapid mutation has led to diverse symptomatology, prompting adjustments in treatment guidelines. This review comprehensively examines repurposed antiviral drug candidates against COVID-19, explores immune responses across different age groups, delves into the mechanisms of COVID-19 vaccines, and discusses potential immunosuppressants. Additionally, the focus extends to Intravenous Immunoglobulin (IVIG), steroids, and anti-cytokine therapy as promising avenues to address cytokine release syndrome (CRS), a critical condition in COVID-19 patients.},
}

Humans
COVID-19/immunology
*SARS-CoV-2/drug effects
*Antiviral Agents/therapeutic use/adverse effects
*COVID-19 Drug Treatment
COVID-19 Vaccines/immunology
*HIV Infections/complications/immunology/drug therapy
Drug Repositioning

@article {pmid41117273,
year = {2025},
author = {Oba, S and Hosoya, T and Iwai, H and Yasuda, S},
title = {Long COVID: mechanisms of disease, multisystem sequelae, and prospects for treatment.},
journal = {Immunological medicine},
volume = {},
number = {},
pages = {1-24},
doi = {10.1080/25785826.2025.2570902},
pmid = {41117273},
issn = {2578-5826},
abstract = {Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.},
}

@article {pmid40676931,
year = {2025},
author = {Abdul-Azees, PA and Marinkovic, M and Singh, BB and Dean, DD and Chen, XD and Goldberg, MP and Restrepo, MI and Loomer, PM and Yeh, CK},
title = {The Impact of Aging Oral Health on Long COVID-19.},
journal = {Journal of dental research},
volume = {104},
number = {12},
pages = {1294-1303},
doi = {10.1177/00220345251349805},
pmid = {40676931},
issn = {1544-0591},
mesh = {Humans ; *COVID-19/complications/immunology ; *Oral Health ; *Aging/physiology/immunology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Mouth Diseases/virology ; },
abstract = {At least 10% of individuals infected with SARS-CoV-2 develop a variety of multisystem symptoms lasting more than 12 wk known as postacute sequelae of COVID-19 (PASC) or "long COVID." While the precise pathogenesis of PASC remains unclear, immune dysregulation is widely recognized as a key factor. Moreover, PASC disproportionately affects older individuals who are prone to age-related immune system decline, which further exacerbates the risk and severity of PASC. The oral cavity, a primary site for initial SARS-CoV-2 infection, may contribute to the development and persistence of PASC. Emerging evidence suggests that changes in age-related oral health, such as periodontitis, salivary gland (SG) dysfunction, and gustatory and olfactory impairments, may create an environment conducive to forming an oral reservoir of intact virus or viral antigens, which may contribute to the chronicity of PASC. Alternatively, the pathogenesis of PASC may increase the risk of a wide range of oral health issues, such as dental diseases, dry mouth, and sensory dysfunction (e.g., taste and smell) that are frequently reported by patients with PASC. This review highlights how aging facilitates oral SARS-CoV-2 infection, co-infection with other viruses may drive PASC in aging patients, aging and PASC dysregulate the oral microbiome, SARS-CoV-2 infection promotes molecular mechanisms involved in oral tissue aging, aging oral health affects susceptibility to developing PASC, and inflammation associated with PASC exacerbates dysregulation of metabolic/enzymatic pathways of aging oral mucosa and diseases of the periodontal apparatus, SGs, and taste. It underscores the urgent need to comprehensively address the interplay between aging oral health and PASC, which will help mitigate long-term complications and improve overall health outcomes for affected individuals.},
}

Humans
*COVID-19/complications/immunology
*Oral Health
*Aging/physiology/immunology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Mouth Diseases/virology

@article {pmid41108594,
year = {2025},
author = {Akbar, N and Phadke, S and Mehelay, S and Pullattayil, AK and Fakolade, A and Busse, M},
title = {Considerations of race and ethnicity within rehabilitation studies for post COVID-19 condition: A scoping review.},
journal = {PM & R : the journal of injury, function, and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1002/pmrj.70027},
pmid = {41108594},
issn = {1934-1563},
abstract = {Post COVID-19 condition (PCC) or long COVID disproportionately affects racial and ethnic minority communities. There are a growing number of rehabilitation studies for PCC, however, it has yet to be determined whether existing studies take race and ethnicity into account in their study designs and whether existing rehabilitative approaches are equally effective across diverse racial and ethnic groups. The objective of this study was to describe the extent to which rehabilitation studies of PCC consider race and ethnicity in defining eligibility criteria, planning recruitment strategies, designing intervention delivery and adherence promoting approaches, selecting outcome measures, and reporting results. Of the 4845 studies screened, 23 met eligibility criteria and were included in this review. The most common reason for exclusion was a lack of mention of race or ethnicity anywhere within the article. Among the 23 studies included, 13 studies provided data on the race and/or ethnicity characteristics of their sample, with 88% of participants across all of these studies being White. Less than 25% of studies described the incorporation of race and/or ethnicity in their recruitment strategies (n = 3, 13%) or data analysis (n = 5, 22%). Greater racial and ethnic diversity is needed within rehabilitation studies for PCC as there is currently a significant underrepresentation of racial and ethnic minorities in existing studies. Overall, more PCC rehabilitation studies need to incorporate race and ethnicity into their study designs as it is not well understood whether existing rehabilitation strategies are equally effective across different racial and ethnic groups.},
}

@article {pmid41104805,
year = {2025},
author = {Luo, S and Lai, LY and Zhu, R and Gao, Y and Zhao, Z},
title = {Prevalence and duration of common symptoms in people with long COVID: a systematic review and meta-analysis.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04282},
doi = {10.7189/jogh.15.04282},
pmid = {41104805},
issn = {2047-2986},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Prevalence ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Time Factors ; Fatigue/epidemiology ; },
abstract = {BACKGROUND: During the COVID-19 pandemic, an increasing number of patients have reported persistent symptoms after recovery, a phenomenon known as long COVID. These symptoms may persist for weeks or months, affecting the patient's daily life and health. To systematically understand the long-term impact of long COVID, this study conducted a systematic review and meta-analysis. This study aims to determine the long-term effects of long COVID by identifying, evaluating and summarising the incidence and duration of persistent symptoms after the acute phase of COVID-19.

METHOD: We searched PubMed, Embase, and medRxiv up to August 2021 for articles and preprints presenting original research on the symptoms of long COVID. Following title/abstract and full-text screening, based on the PICOS framework, we excluded articles that did not clearly report on diagnoses, reported on symptoms lasting less than four weeks, lacked epidemiological data, or did not provide complete data. We assessed the bias of included studies using the Newcastle-Ottawa Scale. For effects reported in more than two studies, we performed meta-analysis of prevalence, and also counted the duration of each symptom.

RESULTS: We included 19 observational studies in the meta-analysis, through which we determined the incidence and duration of five common long COVID symptoms, including cognitive/memory/attention disorders (36%, unreported duration), fatigue (34%, 5.5 months), mental health problems (including anxiety and depression, 31%, 3.5-3.8 months), and dyspnoea (24%, 6.52 months) and chest pain (23%, 2 months).

CONCLUSIONS: The symptoms of long COVID usually persist after the acute phase of COVID-19. The clustering of long COVID symptoms provides a direction for studying the aetiology, diagnosis, and management of post-COVID conditions. Our findings provide important baseline data for the prevention and treatment of long COVID.},
}

Humans
*COVID-19/epidemiology/complications
Prevalence
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Time Factors
Fatigue/epidemiology

@article {pmid41094377,
year = {2025},
author = {Arab, Z and Shayanfar, N and Mojaver, MR and Khormali, M and Boskabady, MH and Niazmand, S},
title = {Cardiopulmonary crosstalk in Long COVID: a systematic review of emerging evidence.},
journal = {BMC cardiovascular disorders},
volume = {25},
number = {1},
pages = {742},
pmid = {41094377},
issn = {1471-2261},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; *Endothelium, Vascular/physiopathology ; *Pulmonary Fibrosis/physiopathology ; },
abstract = {BACKGROUND: Long COVID is a complex, multisystem syndrome with significant cardiopulmonary implications. Persistent inflammation, endothelial dysfunction, and microvascular injury contribute to prolonged symptoms such as dyspnea, chest pain, and exercise intolerance. Despite growing recognition of these complications, the underlying mechanisms of cardiopulmonary interactions remain poorly understood.

METHODS: A comprehensive literature search was conducted on PubMed, Scopus, Google Scholar, and Web of Science covering studies from 2019 to 2025. Keywords included "Long COVID", "cardiopulmonary interaction", "pulmonary fibrosis", "myocardial inflammation", and "endothelial dysfunction". A total of 102 articles were included, comprising 65 original research studies and 37 review articles.

RESULTS: Pulmonary sequelae, such as fibrotic remodeling, persistent hypoxia, and microthrombosis, impose significant strain on the cardiovascular system, exacerbating myocardial inflammation, arrhythmias, and endothelial dysfunction. Shared mechanisms, such as oxidative stress, immune dysregulation, and neurohumoral activation, create a vicious cycle of sustained cardiopulmonary impairment. The disruption of the renin-angiotensin-aldosterone system (RAAS) further contributes to systemic vascular dysregulation.

CONCLUSION: A deeper understanding of cardiopulmonary interactions in Long COVID is essential for developing effective management strategies. Targeting inflammatory pathways, restoring endothelial function, and addressing autonomic instability may provide therapeutic benefits. As the long-term impact of this syndrome continues to evolve, further research is needed to refine treatment approaches and mitigate its burden on global health.},
}

Humans
*COVID-19/physiopathology/complications
Renin-Angiotensin System
Post-Acute COVID-19 Syndrome
SARS-CoV-2
*Endothelium, Vascular/physiopathology
*Pulmonary Fibrosis/physiopathology

@article {pmid41091675,
year = {2025},
author = {Nagra, G and Ezeugwu, VE and Bostick, GP and Branton, E and Dennett, L and Drake, K and Durand-Moreau, Q and Guptill, C and Hall, M and Ho, C and Hung, P and Khan, A and Lam, GY and Nowrouzi-Kia, B and Gross, DP},
title = {Return-to-work for people living with long COVID: A scoping review of interventions and recommendations.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0321891},
doi = {10.1371/journal.pone.0321891},
pmid = {41091675},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; *Return to Work ; SARS-CoV-2/isolation & purification ; },
abstract = {INTRODUCTION: Long COVID is characterized by the presence of new onset or persistent symptoms 3 months after a suspected or confirmed history of SARS-CoV-2 infection. It is a complex and multi-faceted condition that affects people in different ways. Long COVID affects individuals' labour market participation. While some cannot work, others may return to work (RTW) in a limited capacity. Determining what rehabilitation or related strategies are safe and effective for facilitating RTW is necessary.

OBJECTIVES: To synthesize evidence on RTW interventions for people living with Long COVID and to identify 'promising' interventions for enhancing work ability and RTW.

METHODS: We followed Arksey & O'Malley's methodology and the PRISMA extension for scoping reviews. Five electronic bibliographic databases and grey literature were searched. The literature search included various study designs, such as randomized controlled trials (RCT), quasi-experimental designs, and observational studies as well as clinical practice guidelines (CPGs). Two reviewers conducted screening and data extraction, with disagreements resolved through consensus. Intervention studies were categorized as promising (statistically significant RTW outcomes or ≥ 50% RTW), somewhat promising (20% to < 50% RTW), not promising (non-statistically significant RTW outcomes or < 20% RTW), or uncertain (did not specify proportion of RTW).

RESULTS: Twelve CPGs and nineteen intervention studies were identified. Of the intervention studies, 5 were cohort studies, 3 quasi-experimental studies, 4 observational, 2 interventional, 3 RCTs, and 2 case reports. Promising interventions included multimodal and interdisciplinary work-focused rehabilitation, multidisciplinary inpatient and outpatient rehabilitation, psychoeducation, pacing, and breathing strategies, shifting focus from symptom monitoring to optimizing functional outcomes, enhanced external counterpulsation inflatable pressure to improve blood flow, and constraint-induced cognitive therapy.

CONCLUSION: Many uncertainties remain regarding which RTW interventions are effective or the optimal characteristics of these interventions.},
}

Humans
*COVID-19/rehabilitation/epidemiology
*Return to Work
SARS-CoV-2/isolation & purification

@article {pmid41089587,
year = {2025},
author = {Albazee, E and Alajmi, SA and Alkandari, AM and Aladwani, AN and Alenezi, YY and Alsaeed, MA and Uqlah, B and Abu-Zaid, A},
title = {Platelet-Rich Plasma for COVID-19-Related Olfactory Dysfunction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e94386},
pmid = {41089587},
issn = {2168-8184},
abstract = {A notable rise in olfactory dysfunction (OD) prevalence has been observed since the COVID-19 pandemic. COVID-19-related OD is associated with several consequences, especially deteriorated quality of life. Hence, several treatment options have been investigated, with platelet-rich plasma (PRP) showing promising results. A systematic review and meta-analysis summarizing randomized controlled trial (RCT) evidence were retrieved from PubMed, Google Scholar, Scopus, and Web of Science up to June 2025. The risk of bias was assessed using the Cochrane Risk of Bias 2 assessment tool. Data were analyzed using Stata MP version 18 (StataCorp LLC, College Station, TX), pooling dichotomous outcomes as relative risks (RRs) and continuous outcomes as standardized mean differences (SMDs), each with 95% confidence intervals (CIs). Four RCTs, including 198 participants, were included in our meta-analysis. PRP significantly improved objective olfactory scores (SMD = 1.86, 95% CI (0.14, 3.57), p = 0.03) and subjective olfactory scores (SMD = 0.92, 95% CI (0.32, 1.51), p < 0.001). Additionally, PRP significantly increased the response rate (RR = 1.79, 95% CI (1.14, 2.81), p = 0.01). PRP was generally well-tolerated across the included trials, with no major adverse events reported. Two RCTs showed an overall low risk of bias, one trial showed some concerns, and another showed a high risk of bias. With uncertain evidence, PRP may improve both objective and subjective smell function and clinical outcomes in people with long COVID-related OD. PRP treatment was reported to be safe, with minor, temporary side effects primarily related to the procedure. Although initial results are promising, the small number of RCTs requires a cautious approach to interpretation.},
}

@article {pmid41089328,
year = {2025},
author = {Blitshteyn, S and Funez-dePagnier, G and Szombathy, A and Hutchinson, M},
title = {Immunotherapies for postural orthostatic tachycardia syndrome, other common autonomic disorders, and Long COVID: current state and future direction.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1647203},
pmid = {41089328},
issn = {2235-2988},
mesh = {Humans ; *Postural Orthostatic Tachycardia Syndrome/therapy/immunology ; *COVID-19/therapy/immunology/complications ; *Immunotherapy/methods/trends ; *Autonomic Nervous System Diseases/therapy/immunology ; Immunoglobulins, Intravenous/therapeutic use ; SARS-CoV-2 ; Plasmapheresis ; Adrenal Cortex Hormones/therapeutic use ; Post-Acute COVID-19 Syndrome ; },
abstract = {Postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope, and orthostatic hypotension are the most common autonomic disorders encountered in clinical practice. The autoimmune etiology and association of these conditions with systemic autoimmune and inflammatory disorders, autonomic neuropathy, and post-acute infectious syndromes, including Long COVID, suggest that immunotherapies should be considered as a therapeutic option, at least in a subset of patients. However, the treatment of common autonomic disorders has traditionally included pharmacologic and non-pharmacologic symptomatic therapies as the standard approach. Unfortunately, these symptomatic therapies have been of limited or insufficient efficacy to meaningfully improve functional status or result in recovery, especially in patients with severe symptoms. Case reports, case series, and clinical experience suggest that intravenous and subcutaneous immunoglobulin, as well as other immunologic therapies (such as plasmapheresis, corticosteroids, and rituximab), may be effective in some patients with severe POTS and other common autonomic disorders who are refractory to standard therapies. In this narrative review, we summarize the literature available on the topic of immunotherapies for POTS, other common autonomic disorders, and Long COVID. We also highlight the need for large, multicenter, placebo-controlled trials of immunoglobulin, plasmapheresis, intermittent corticosteroids, and other repurposed immunotherapies in patients with common autonomic disorders who have significant functional impairment.},
}

Humans
*Postural Orthostatic Tachycardia Syndrome/therapy/immunology
*COVID-19/therapy/immunology/complications
*Immunotherapy/methods/trends
*Autonomic Nervous System Diseases/therapy/immunology
Immunoglobulins, Intravenous/therapeutic use
SARS-CoV-2
Plasmapheresis
Adrenal Cortex Hormones/therapeutic use
Post-Acute COVID-19 Syndrome

@article {pmid41087378,
year = {2025},
author = {Yonker, LM and Dredge, D and Munro, A and Di Chiara, C and Cotugno, N and Buonsenso, D},
title = {The second-order effects that the COVID-19 pandemic has had on pediatric populations.},
journal = {Expert review of anti-infective therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14787210.2025.2575044},
pmid = {41087378},
issn = {1744-8336},
abstract = {INTRODUCTION: There is growing recognition that SARS-CoV-2 can have long-term health consequences that persist beyond acute infection. While the long-term health impact of SARS-CoV-2 is evident in adults and the elderly, the impact on children and adolescents remains under recognized. In this paper, we navigate the second-order post-acute effects that the COVID-19 has had on the pediatric populations, with the exception of mental health implication of social restrictions, out of the scope of this review.

AREAS COVERED: We outline common scenarios related with SARS-CoV-2 infection encountered in pediatric clinical practice, such as in the Multisystem inflammatory syndrome (MIS-C), Long Covid, neurological and autoimmune complications of Covid-19, immunological impact of the viral infection, as well as epidemiological and public health consequences associated with the implementation of non-pharmacological interventions.

EXPERT OPINION: SARS-CoV-2 has had several second-order effects on child health, from a biological, epidemiological, and public health perspective, highlighting the complexity of dealing with new infections and the urgent need to implement multidisciplinary interventions that support the health of people at single person and societal level. Funding on modern surveillance system, preventing strategies and research to better understand and cure post-acute complications of viral infections should be a priority of every funding agency.},
}

@article {pmid41082082,
year = {2025},
author = {Wasim, R},
title = {From infection to intervention: post-acute sequelae of SARS-CoV-2 infection and cardiovascular risk.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41082082},
issn = {1568-5608},
abstract = {COVID is now a worldwide epidemic of non-communicable diseases. The symptoms, which impact several organs, might last for hours, weeks, or even months after the SARS-CoV-2 infection has ended. Electrocardiogram abnormalities (ECG), postural orthostatic tachycardia, and supraventricular or ventricular arrhythmias are among the common signs of long COVID-19. According to data, certain patient groups have persistent, post-infectious perimyocarditis, which may lead to left or right ventricular failure, arterial wall inflammation, or microthrombosis. This information has been made available by cardiac and vasculature imaging, and it may be used to develop efficient treatment plans for the cardiovascular symptoms of long COVID. Long COVID requires a greater understanding of the cellular and molecular processes. There are a variety of approaches that have been put forward, some of which include direct impacts on the heart and others that involve microthrombotic damage to the arteries or heart. When evaluated 3 months after SARS-CoV-2 infection, the currently employed circulating biomarkers, such as coagulation and inflammatory markers, do not serve as a highly predictive predictor for the existence or outcome of long COVID. However, further study is required to better understand the underlying processes and particular biomarkers for future COVID preventive methods.},
}

@article {pmid41076807,
year = {2025},
author = {Domingo, JL},
title = {Differentiating COVID-19 vaccine-related adverse events from long COVID: A comprehensive review of clinical manifestations, pathophysiology, and diagnostic approaches.},
journal = {Vaccine},
volume = {66},
number = {},
pages = {127842},
doi = {10.1016/j.vaccine.2025.127842},
pmid = {41076807},
issn = {1873-2518},
abstract = {The global deployment of COVID-19 vaccines has introduced diagnostic challenges due to overlapping symptoms with long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), prompting a comprehensive review of vaccine safety profiles, long COVID manifestations, and evidence-based differentiation strategies. Through a literature search (PubMed, Scopus, Web of Science) from December 2020 to June 2025, including peer-reviewed studies, clinical trials, and cohort studies, the present review reports that COVID-19 vaccines maintain robust safety, with rare adverse events like myocarditis and thrombosis with thrombocytopenia syndrome, while long COVID affects 10-40 % of SARS-CoV-2 survivors, presenting symptoms such as fatigue, cognitive dysfunction, and dyspnea. Differentiation between these conditions relies on careful analysis of the timing of symptom onset, detailed symptom characterization, and the use of advanced diagnostic tools. Systematic clinical assessment is essential for accurate diagnosis, which is critical for appropriate patient management, maintaining public confidence in vaccination, and guiding future research. Further studies are needed to validate diagnostic biomarkers, develop targeted therapies, and monitor long-term outcomes, with standardized global registries and interdisciplinary collaboration identified as key priorities for improving care and advancing the field.},
}

@article {pmid41073921,
year = {2025},
author = {Takamatsu, N and Kuga, H},
title = {Applicability and adaptation of cognitive behavior therapy for long COVID neuropsychiatric symptoms: a review with insights from ME/CFS.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1275},
pmid = {41073921},
issn = {1471-2334},
support = {JP23K02953//Japan Society for the Promotion of Science/ ; },
}

@article {pmid41073313,
year = {2025},
author = {Wang, MC and Liu, X and Hu, K},
title = {[Intermittent hypoxia exposure in the rehabilitation of long COVID patients].},
journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases},
volume = {48},
number = {10},
pages = {961-964},
doi = {10.3760/cma.j.cn112147-20250601-00295},
pmid = {41073313},
issn = {1001-0939},
support = {JCRCYG-2022-012//Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University/ ; },
mesh = {Humans ; *COVID-19/rehabilitation ; *Hypoxia/rehabilitation ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; },
abstract = {Patients recovering from COVID-19 infection often experience "Long COVID", which is characterized by symptoms such as fatigue, reduced exercise capacity or dyspnea, and cognitive dysfunction. These symptoms negatively impact their quality of life. Currently, there is a lack of widely recognized therapeutic approaches or specific pharmacological interventions for managing these conditions. During intermittent hypoxic exposure (IHE), participants are alternated to hypoxic and normoxic exposure, which induced beneficial adaptive responses in the body. Emerging evidence suggests that IHE can alleviate symptoms of Long COVID through mechanisms such as improving ventilatory function, enhancing cardiopulmonary endurance, modulating immune responses, and reducing inflammation. These effects contribute to an improved quality of life and more holistic recovery, highlighting the promising potential of IHE in managing long COVID.},
}

Humans
*COVID-19/rehabilitation
*Hypoxia/rehabilitation
Quality of Life
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Fatigue

@article {pmid41065846,
year = {2025},
author = {Chang, CC and Li, YH and Chen, HH and Sun, SF},
title = {Clinical applications and molecular mechanisms for intravenous laser blood irradiation: a systematic review.},
journal = {Lasers in medical science},
volume = {40},
number = {1},
pages = {416},
pmid = {41065846},
issn = {1435-604X},
support = {TSGH-D-110120//Tri-Service General Hospital/ ; VTA114-V3-1-2//Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program/ ; VTA114-V3-1-1//Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program/ ; KAFGH-ZY-A-113016//Zuoying Armed Forces General Hospital/ ; KSVGH-114-102//Kaohsiung Veterans General Hospital/ ; },
mesh = {Humans ; *Low-Level Light Therapy/methods ; Cardiovascular Diseases/radiotherapy ; *Blood/radiation effects ; Musculoskeletal Diseases/radiotherapy ; COVID-19 ; Nervous System Diseases/radiotherapy ; },
abstract = {Intravenous Laser Irradiation of Blood (ILIB) is a therapeutic approach that utilizes low-level laser energy to irradiate blood, showing potential clinical value in treating various diseases in recent years. This systematic review aims to comprehensively examine the basic principles, technological developments, biological effects, and clinical applications of ILIB, while analyzing the level of evidence and limitations of existing research. Through searching relevant literature in databases such as PubMed, this study collected research on ILIB applications in musculoskeletal diseases, respiratory diseases, cardiovascular diseases, and neurological disorders. Results indicate that ILIB exhibits multiple biological effects, including improved blood rheological properties, enhanced erythrocyte oxygen-carrying capacity, immune regulation, and reduction of inflammatory responses and oxidative stress. Clinical studies suggest that ILIB has positive therapeutic effects on musculoskeletal pain, sleep disorders, pulmonary diseases, and long COVID-related cognitive impairments. However, existing research still has limitations such as small sample sizes, lack of large-scale randomized controlled trials, and non-standardized dosage parameters. Future research should focus on developing standardized treatment protocols, exploring mechanisms of action in depth, and strategies for combining with conventional therapies to further establish ILIB's position in clinical practice.},
}

Humans
*Low-Level Light Therapy/methods
Cardiovascular Diseases/radiotherapy
*Blood/radiation effects
Musculoskeletal Diseases/radiotherapy
COVID-19
Nervous System Diseases/radiotherapy

@article {pmid41062170,
year = {2025},
author = {Houweling, L and Rots, I and Bloemsma, LD and van Vorstenbosch, R and Del Motto, S and Vermeulen, RCH and Maitland-Van der Zee, AH and Golebski, K and Downward, GS},
title = {Impact of air pollution on COVID-19 severity: a systematic review of underlying biological mechanisms.},
journal = {European respiratory review : an official journal of the European Respiratory Society},
volume = {34},
number = {178},
pages = {},
doi = {10.1183/16000617.0070-2025},
pmid = {41062170},
issn = {1600-0617},
mesh = {Humans ; *COVID-19/epidemiology/immunology/virology ; *Air Pollution/adverse effects ; Severity of Illness Index ; SARS-CoV-2 ; Particulate Matter/adverse effects ; *Air Pollutants/adverse effects ; },
abstract = {BACKGROUND: Our recent systematic review highlighted key associations between ambient air pollution (AAP) exposure and COVID-19 severity. This systematic review aims to summarise toxicological studies on the biological mechanisms underlying these associations.

METHODS: On 17 July 2025, PubMed, Embase, Scopus and Web of Science were searched for in vitro, in vivo and in silico studies that examined the biological mechanisms of AAP exposure on COVID-19 health outcomes. Two independent reviewers engaged in the selection and data extraction process. The methodological quality of the included studies was assessed with the Toxicological Data Reliability Assessment Tool. The Integrated Network and Dynamical Reasoning Assembler (INDRA) was used to provide visual biomechanistic summaries of the included studies by creating knowledge graphs of the described mechanisms.

RESULTS: A total of 18 studies were included in this review. Findings consistently indicated that AAP exposure can worsen COVID-19 severity through two key mechanisms 1) increased expression of viral entry factors (e.g. angiotensin-converting enzyme 2 and transmembrane serine protease 2), facilitating infection, and 2) immune dysregulation, resulting in increased inflammation and oxidative stress. These key mechanisms were also identified in the INDRA networks. While studies commonly focused on particulate matter (n=15), similar effects were seen with ultrafine particles and ozone.

CONCLUSION: These findings highlight the impact of AAP exposure on COVID-19 health outcomes on the molecular level. The findings of this review illustrate the urgent need for air quality improvements to help shape public health strategies to reduce and prevent future health impacts caused by AAP exposure.},
}

Humans
*COVID-19/epidemiology/immunology/virology
*Air Pollution/adverse effects
Severity of Illness Index
SARS-CoV-2
Particulate Matter/adverse effects
*Air Pollutants/adverse effects

@article {pmid41062137,
year = {2025},
author = {Daniels, S and Wei, H and McElvenny, DM and van Tongeren, M and Bramwell, D and Coleman, A and Forde, D and Wiggans, R},
title = {Return to work with long COVID: a rapid review of support and challenges.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e101698},
doi = {10.1136/bmjopen-2025-101698},
pmid = {41062137},
issn = {2044-6055},
mesh = {Humans ; *Return to Work ; *COVID-19/rehabilitation ; SARS-CoV-2 ; Workplace ; },
abstract = {OBJECTIVES: To explore existing evidence for the provision of support for return to work (RTW) in long COVID (LC) patients and the barriers and facilitators to taking up this support.

DESIGN: A rapid review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study was preregistered in PROSPERO (ID: CRD42023478126).

DATA SOURCES: Searches were completed in June 2024 across major databases including MEDLINE, Embase, PsycINFO, evidence-based medicine reviews, Web of Science and Google Scholar.

ELIGIBILITY CRITERIA: Included studies focused on people with LC (PwLC) symptoms lasting over 12 weeks and addressed either: (1) non-workplace- or workplace-based support for RTW and/or (2) barriers and facilitators to RTW in this population.

DATA EXTRACTION AND SYNTHESIS: A quality assessment was conducted using the JBI Systematic Reviews critical appraisal tool. The data were summarised in tabular format and a narrative synthesis.

RESULTS: Twenty-five studies were included. While many studies demonstrated rigorous methodologies and low risk of bias levels, some had high and medium risk levels. Non-workplace-based support was mostly measured quantitatively and included interdisciplinary healthcare programmes, clinical interventions and rehabilitation programmes focusing on pacing and breathing strategies. Compensation and insurance schemes were important funders of these interventions.Workplace-based support was mostly measured qualitatively. Barriers to the provision of support at organisational level included lack of understanding of LC symptoms, insufficient workplace guidance and educational gaps among managers. Individual barriers included threat of income loss, remote working and disconnection from the workplace. Facilitators for support included recognition and validation of LC and its symptoms, and eligibility for disability benefits associated with work.

CONCLUSIONS: RTW is an important outcome of health-related absence and should be systematically recorded in studies of PwLC. The heterogeneity and unpredictability of LC symptoms create challenges for supporting working age populations. Further research is crucial to better understand the specific RTW needs for PwLC and address potential barriers and facilitators to workplace-based support, particularly through interventions, organisational practices and employ-led policies that enable sustained RTW. Consistent guidelines on LC's definition and disability status may facilitate the provision of support and the development of interventions.

PROSPERO REGISTRATION NUMBER: CRD42023478126.},
}

Humans
*Return to Work
*COVID-19/rehabilitation
SARS-CoV-2
Workplace

@article {pmid41057923,
year = {2025},
author = {Gidey, K and Niriayo, YL and Asgedom, SW and Lubetkin, E},
title = {Health-related quality of life in COVID-19 patients: a systematic review and meta-analysis of EQ-5D studies.},
journal = {Health and quality of life outcomes},
volume = {23},
number = {1},
pages = {97},
pmid = {41057923},
issn = {1477-7525},
support = {1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; 1627-RA//EuroQol Research Foundation/ ; },
abstract = {BACKGROUND: COVID-19 has affected millions globally, with a significant proportion experiencing long-COVID and impaired health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to synthesize the existing literature on HRQoL in COVID-19 patients.

METHODS: We conducted a systematic search of PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for studies published between December 2019 and March 2025. Eligible studies were peer-reviewed and assessed HRQoL in COVID-19 patients using the EQ-5D instrument. Study quality and risk of bias were evaluated using the Newcastle-Ottawa Scale. Pooled health utility values were estimated using a random-effects model, and heterogeneity was assessed via I[2] statistics. Predictors of poor HRQoL were qualitatively narrated.

RESULTS: Out of 3539 references, 187 studies with 116,525 participants were analyzed. The majority (80.2%) used the EQ-5D-5 L version. The pooled mean EQ-5D utility score was 0.76 (95% CI 0.74-0.79, I[2] = 99.9%) while the mean EQ-5D Visual Analogue Scale (VAS) score was 70.76 (95% CI 68.48-73.04; I[2] = 99.7%). Pain/discomfort and anxiety/depression were the most affected domains, reported by 51% and 46% of patients, respectively. Subgroup analysis showed significant differences in HRQoL based on national income status (p = 0.038) and geographic region (p < 0.001). Common predictors of lower HRQoL included older age, female gender, disease severity, comorbidities, and post-COVID-19 symptoms.

CONCLUSION: This systematic review demonstrates a substantial reduction in HRQoL among COVID-19 patients compared to the general population. The pooled utility values of COVID-19 contribute to understanding patients' HRQoL and can assist in calculating Quality-Adjusted Life Years. This provides essential data for future economic evaluations and informs health policy decisions.},
}

@article {pmid41057797,
year = {2025},
author = {Bessaguet, C and Bonilla, A and Polin, C and Lacroix, A and Cartz-Piver, L},
title = {A systematic review to find link between past psychiatric history and development of long covid.},
journal = {BMC psychiatry},
volume = {25},
number = {1},
pages = {942},
pmid = {41057797},
issn = {1471-244X},
abstract = {BACKGROUND: Covid-19 is a pandemic acute infectious disease that emerged in 2019. It is estimated that 10-20% will develop persistent symptoms, known as long Covid or post-Covid syndrome. The risk factors for the development of this syndrome are still being studied. Psychosocial factors are known to increase the duration and severity of respiratory infections.

AIMS: (i) to review current knowledge of the link between past psychiatric history and the development of long Covid; (ii) to obtain information on the psychological experience of the initial infection; (iii) to establish a link between the presence of psychiatric symptoms during the acute phase and the development of long Covid.

METHOD: We conducted a systematic review according to PRISMA standards using the Pubmed, Science Direct and Scopus databases. We included observational studies of adult subjects with long Covid whose psychiatric and/or addictive histories were searched.

RESULTS: A total of 36 articles were included in our review. Depression and anxiety appear to be risk factors for the development of long Covid. There is no consensus on the contribution of smoking to the onset of the syndrome. The negative psychological experience of the acute infection favours the persistence of symptoms. Psychological symptoms during the acute phase, studied in only one of our articles, seem to contribute to the persistence of concentration and attention problems.

CONCLUSION: Psychological comorbidities pre-existing COVID-19 infection, in particular depression and anxiety, as well as a poor psychological experience of the acute phase, may favour the development of long Covid.

TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42023391720.},
}

@article {pmid41056092,
year = {2025},
author = {Newby, MJ and Haracz, K and Lane, SJ and Tona, J},
title = {Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Occupational Performance: A Scoping Review.},
journal = {The American journal of occupational therapy : official publication of the American Occupational Therapy Association},
volume = {79},
number = {6},
pages = {},
doi = {10.5014/ajot.2025.051238},
pmid = {41056092},
issn = {0272-9490},
mesh = {Humans ; *Occupational Therapy/methods ; Child ; *Obsessive-Compulsive Disorder/rehabilitation ; *Activities of Daily Living ; Social Participation ; Autoimmune Diseases ; },
abstract = {IMPORTANCE: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a neuroimmune condition that significantly affects children's occupational performance across multiple domains. However, occupational performance is often overlooked in current PANS clinical frameworks, despite its critical role in daily functioning and well-being.

OBJECTIVE: To synthesize evidence on the occupational performance challenges experienced by children with PANS, the tools used to assess these challenges, and occupational therapy interventions used with these children.

DATA SOURCES: MEDLINE, CINAHL, Cochrane Library, PsycINFO, SCOPUS, ERIC, and EMBASE were searched from their inception through May 17, 2024.

Peer-reviewed studies addressing PANS and occupational performance were included, with data categorized using the Occupational Therapy Practice Framework, 4th Edition.

FINDINGS: Of 3,431 records, 40 studies met inclusion criteria. Occupational performance challenges centered on communication, nutrition, education, rest/sleep, social participation, and toileting, with limited data on bathing, dressing, personal hygiene, and play and leisure. Assessments emphasized client factors, rarely using occupation-based tools. Only 2 studies mentioned occupational therapy interventions.

CONCLUSIONS AND RELEVANCE: PANS has a pervasive impact on children's occupational performance, highlighting the urgent need to prioritize it within clinical frameworks. Future research should focus on occupation-based intervention studies and assessments to enhance outcomes for children with PANS. Plain-Language Summary: Pediatric acute-onset neuropsychiatric syndrome (PANS) causes sudden, severe symptoms, such as obsessive-compulsive behaviors, eating difficulties, sensory and motor changes, and developmental regression, which significantly disrupt children's ability to perform daily activities. This study included 40 research articles addressing what is known about the impact of PANS on children's daily functioning and the role of occupational therapy in managing challenges. Results showed that most studies focused on communication, nutrition, education, sleep, social, and toileting challenges, but few addressed other daily tasks like bathing, dressing, personal hygiene, and play or leisure. Despite identified challenges, only two studies mentioned occupational therapy interventions, highlighting a major gap in the evidence. Assessments focused mainly on a child's skills and challenges, rather than looking at how the child participates in everyday activities. The findings highlight the need to better understand the challenges children with PANS face in their everyday activities and to provide practical strategies to help them succeed. Positionality Statement: Newby is a pediatric occupational therapist and researcher with both professional and personal experience of PANS. Her clinical work with children diagnosed with PANS, along with personal experience supporting a family member with this condition, has deepened her interest in the episodic fluctuations in occupational performance that occur during periods of exacerbation and remission. Haracz is an occupational therapist, academic, and researcher with a focus on mental health and the intersection between physical and psychological well-being. Lane is an occupational therapist, academic, and researcher who specializes in the neuroscience of developmental conditions and how sensory processing differences affect children's engagement in daily occupations. Tona is an occupational therapist and educational psychologist whose interest in neuroinflammatory disorders emerged following a family member's diagnosis with PANS. Her research explores the characteristics of PANS, treatment access, caregiver burden, and the role of occupational therapy in improving participation in both PANS and long-COVID populations.},
}

Humans
*Occupational Therapy/methods
Child
*Obsessive-Compulsive Disorder/rehabilitation
*Activities of Daily Living
Social Participation
Autoimmune Diseases

@article {pmid41049923,
year = {2025},
author = {Pedraza, A and Bonnice, S and Won, MN and Kesselman, MM and Demory Beckler, M},
title = {Impact of COVID-19 on the Gut Microbiome: A Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91470},
pmid = {41049923},
issn = {2168-8184},
abstract = {Coronavirus Disease 2019 (COVID-19) has resulted in over 6 million deaths worldwide in fewer than four years and is a result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The protein that mediates SARS-CoV-2 host cell entry is the angiotensin-converting enzyme 2 (ACE2), which is highly expressed on the membrane of gastrointestinal (GI) cells. Consequently, infection can lead to direct damage to the GI tract and gut dysbiosis, which is associated with an imbalance of microbiota, inflammation, and other systemic infections and diseases. In this review, we will focus on the impact of COVID-19 on the GI system. We will examine the pathophysiology of gut dysbiosis in COVID-19 patients, as well as emphasize the significance of probiotics in addressing this condition. Additionally, we will identify key areas of interest that warrant further investigation.},
}

@article {pmid41049897,
year = {2025},
author = {Castellano, B and Castellano, C and Sobczak, A and Khanna, D},
title = {Long-Term Manifestations of COVID-19: A Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91492},
pmid = {41049897},
issn = {2168-8184},
abstract = {Although most coronavirus disease 2019 (COVID-19) cases resolve within a few weeks after the onset of infection, a considerable number of patients still suffer from prolonged or recurrent symptoms evident after weeks or months post-COVID-19 recovery. This paper analyzed the current literature related to long-term manifestations of COVID-19 and aimed to identify the common symptoms reported four weeks or more after the initial onset of the disease. COVID-19 has been shown to have lasting systemic effects on an array of organ systems, such as the lungs, heart, brain, and gastrointestinal systems. Common symptoms include, but are not limited to, fatigue, brain fog, respiratory difficulties, and loss of taste and smell. The impact of COVID-19 on multiple organ systems is thought to be associated with its ability to bind angiotensin-converting enzyme 2 (ACE2) receptors throughout the body and promote cytokine release. This study provides insight into common long-term manifestations of COVID-19. Future studies should look at how long COVID-19 syndrome affects various subpopulations differently.},
}

@article {pmid41048263,
year = {2025},
author = {Verma, A and Naidu, SV and Sulthana, H and Ullah, A and Shabil, M and Sah, R and Mehta, R and Jan, A and Ain, NU and Rahim, A and Abu Nahla, U},
title = {Musculoskeletal manifestations in post-acute sequelae of SARS-CoV-2 infection: a systematic review and meta-analysis.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1662953},
pmid = {41048263},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Musculoskeletal Diseases/epidemiology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Prevalence ; Incidence ; Myalgia/epidemiology ; },
abstract = {BACKGROUND: The COVID-19 pandemic has highlighted a spectrum of long-term sequelae, with musculoskeletal symptoms being a substantial component of Post-Acute Sequelae of SARS-CoV-2 infection (PASC). This systematic review and meta-analysis aimed to evaluate the incidence and nature of musculoskeletal manifestations in individuals recovering from COVID-19.

METHODS: A systematic search across PubMed, Embase, and Web of Science was performed up to February 15, 2024, to identify studies reporting on musculoskeletal symptoms post-COVID-19. Observational studies which reported any musculoskeletal symptoms of PASC were included. Data were pooled using a random-effects model to calculate the incidence of symptoms, with subgroup analyses based on time since infection. Statistical analysis were conducted in R software (V 4.3).

RESULTS: Sixty-four studies were included, demonstrating a pooled prevalence of muscle pain at 28% (95% CI: 22%-35%), which increased to 25.9% (95% CI: 20.7%-31.7%) at 12 months post-infection. Joint pain showed a pooled prevalence of 14.8% (95% CI: 10.6%-20.2%), with no significant temporal change. Muscle weakness was observed in 12.9% (95% CI: 4.2%-32.9%) of patients. Notable heterogeneity was observed across studies (I [2] > 89% for all symptoms).

CONCLUSION: Musculoskeletal symptoms are prevalent in individuals with PASC, with muscle pain being the most common. The findings highlight the need for comprehensive clinical management and continuous research to create targeted treatments and revise care protocols as the pandemic evolves.},
}

Humans
*COVID-19/complications/epidemiology
*Musculoskeletal Diseases/epidemiology/etiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Prevalence
Incidence
Myalgia/epidemiology

@article {pmid41038267,
year = {2025},
author = {Thomas, D and Yang, PC and Wu, JC and Sayed, N},
title = {Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.},
journal = {Journal of molecular and cellular cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.yjmcc.2025.09.008},
pmid = {41038267},
issn = {1095-8584},
abstract = {The COVID-19 pandemic has revealed that the impact of SARS-CoV-2 infection extends well beyond the acute phase, with long-term sequelae affecting multiple organ systems, most notably, the cardiovascular system. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms such as fatigue, dyspnea, chest pain, and palpitations, which can last for months or even years after initial recovery. Increasing evidence implicates immune dysregulation, endothelial dysfunction, persistent viral antigens, and coagulopathy as central drivers of cardiovascular complications. Mechanistic studies demonstrate that direct viral infection of cardiac and vascular cells, along with autoantibody formation and cytokine-mediated injury, contribute to myocardial inflammation, fibrosis, and arrhythmias. Sex-based immunological differences and underlying comorbidities further influence individual susceptibility and disease trajectory. Large-scale epidemiological studies have confirmed significantly increased risks of pericarditis, cardiomyopathy, dysrhythmias, and heart failure among COVID-19 survivors. In parallel, the emergence of advanced preclinical platforms, including patient-derived induced pluripotent stem cell (iPSC)-based cardiac organoids, engineered heart tissues, and organ-on-a-chip systems has enabled mechanistic dissection of Long COVID pathophysiology. These human-relevant models, when integrated with clinical datasets and artificial intelligence (AI)-driven analytics, offer powerful tools for biomarker discovery, risk stratification, and precision therapeutic development. This review synthesizes the current understanding of cardiovascular involvement in Long COVID, highlights key mechanistic insights from both clinical and preclinical studies, and outlines future directions for diagnostic and therapeutic innovation.},
}

@article {pmid40660830,
year = {2025},
author = {Pagliano, P and Salzano, F and D'Amore, C and Spera, A and Conti, V and Folliero, V and Franci, G and Ascione, T},
title = {How do drug discovery scientists address the unmet need of long COVID syndrome therapeutics and what more can be done?.},
journal = {Expert opinion on drug discovery},
volume = {20},
number = {10},
pages = {1251-1265},
doi = {10.1080/17460441.2025.2534056},
pmid = {40660830},
issn = {1746-045X},
mesh = {Humans ; *COVID-19/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Drug Discovery/methods ; *COVID-19 Drug Treatment ; *Antiviral Agents/pharmacology/therapeutic use/administration & dosage ; COVID-19 Vaccines/administration & dosage ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Long COVID (LC), also known as post-acute COVID-19 syndrome (PASC), has emerged as a significant public health concern characterized by persistent symptoms following SARS-CoV-2 infection. This condition affects regardless of initial illness severity and can significantly impair daily functioning. Understanding the implications of LC is crucial, given that approximately 6.9 % of adults reported related symptoms in 2022, with increased prevalence among women and individuals of Hispanic descent. The pathogenesis of LC is multifactorial, involving mechanisms such as endothelial dysfunction, chronic inflammation, immune dysregulation, and potential viral persistence. The clinical manifestations include fatigue, cognitive impairment, musculoskeletal pain, and sleep disturbances. Current research emphasizes the importance of early antiviral interventions and vaccines to mitigate the risk of developing LC. Despite promising therapies like anti-inflammatory agents and metabolic enhancers, the lack of established biomarkers complicates diagnosis and treatment.

AREAS COVERED: The authors provide an overview of the pathogenesis of LC and briefly review the currently available therapy. The authors then give their perspectives on how best future drug discovery efforts can be utilized to address the current demand for novel LC therapeutics to reduce the burden of this public health problem.

EXPERT OPINION: Progress has been made in understanding the pathophysiology and potential treatment options, as well as in establishing reliable biomarkers for potential tailored strategies. Future research should prioritize both pharmacological and non-pharmacological interventions to enhance patient outcomes and quality of life. Addressing these challenges is essential for developing comprehensive care protocols for individuals affected by LC.},
}

Humans
*COVID-19/complications/physiopathology
Post-Acute COVID-19 Syndrome
*Drug Discovery/methods
*COVID-19 Drug Treatment
*Antiviral Agents/pharmacology/therapeutic use/administration & dosage
COVID-19 Vaccines/administration & dosage
SARS-CoV-2

@article {pmid41030634,
year = {2025},
author = {Johnson, BL},
title = {"In-Flu-Enza and Out-Flew Hair:" Post-Epidemic Health and the Importance of the History of Epidemics.},
journal = {The Yale journal of biology and medicine},
volume = {98},
number = {3},
pages = {341-348},
pmid = {41030634},
issn = {1551-4056},
mesh = {Humans ; *COVID-19/epidemiology/history ; History, 20th Century ; *Influenza, Human/epidemiology/history ; SARS-CoV-2 ; *Epidemics/history ; Pandemics/history ; History, 21st Century ; Influenza Pandemic, 1918-1919/history ; },
abstract = {When COVID-19 survivors reported ongoing symptoms or new health concerns following their infections in 2020 and early 2021, many medical practitioners and health agencies questioned the connection between novel viruses and long-term health impacts. Medical historians studying epidemics understand the connection between viral infection and health complications emerging immediately or years or decades later. In this essay, I explore the similarities between the medical fallout of the 1918 influenza and COVID-19 pandemics. Despite the differences between the viruses, these novel strains produced similar medium- and long-term health difficulties, including cardiovascular dysfunction and crushing fatigue. As I demonstrate, a significant difference between these two pandemics is in the response by medical practitioners. Following influenza, practitioners expected new and worsening health issues and took their patients' complaints seriously, offering support through food delivery, convalescent care, specialist oversight, and in-home nursing. Early in the COVID-19 pandemic, many practitioners characterized ongoing or new symptoms as anxiety. Patients led efforts to recognize Long COVID as an authentic medical condition, and today, physicians around the country refer their patients to Long COVID clinics. The value of medical history is apparent in this comparison-if practitioners understand how historical epidemics impacted various populations, they expect that in the epidemic aftermath or the period following an acute epidemic crisis, not all patients get well. Including the history of epidemics in public health education, continuing education programming, and even medical school curricula can resist epidemic erasure and empower medical practitioners to expect the unexpected.},
}

Humans
*COVID-19/epidemiology/history
History, 20th Century
*Influenza, Human/epidemiology/history
SARS-CoV-2
*Epidemics/history
Pandemics/history
History, 21st Century
Influenza Pandemic, 1918-1919/history

@article {pmid41011507,
year = {2025},
author = {Maddaloni, L and Bugani, G and Fracella, M and Bitossi, C and D'Auria, A and Aloisi, F and Azri, A and Santinelli, L and Ben M'Hadheb, M and Pierangeli, A and Frasca, F and Scagnolari, C},
title = {Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092176},
pmid = {41011507},
issn = {2076-2607},
support = {RM124190A260C1F0//Sapienza University of Rome/ ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recognized by pattern recognition receptors (PRRs), which play a vital role in triggering innate immune responses such as the production of type I and III interferons (IFNs). While modest PRR activation helps to defend against SARS-CoV-2, excessive or sustained activation can cause harmful inflammation and contribute to severe Coronavirus Disease 2019 (COVID-19). Altered expression of Toll-like receptors (TLRs), which are among the most important members of the PRR family members, particularly TLRs 2, 3, 4, 7, 8 and 9, has been strongly linked to COVID-19 severity. Furthermore, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), collectively known as RLRs (RIG-I-like receptors), act as sensors that detect SARS-CoV-2 RNA. The expression of these receptors, as well as that of different DNA sensors, varies in patients infected with SARS-CoV-2. Changes in PRR expression, particularly that of TLRs, cyclic GMP-AMP synthase (cGAS), and the stimulator of interferon genes (STING), have also been shown to play a role in the development and persistence of long COVID (LC). However, SARS-CoV-2 has evolved strategies to evade PRR recognition and subsequent signaling pathway activation, contributing to the IFN response dysregulation observed in SARS-CoV-2-infected patients. Nevertheless, PRR agonists and antagonists remain promising therapeutic targets for SARS-CoV-2 infection. This review aims to describe the PRRs involved in recognizing SARS-CoV-2, explore their expression during SARS-CoV-2 infection, and examine their role in determining the severity of both COVID-19 and long-term manifestations of the disease. It also describes the strategies developed by SARS-CoV-2 to evade PRR recognition and activation. Moreover, given the considerable interest in modulating PRR activity as a novel immunotherapy approach, this review will provide a description of PRR agonists and antagonists that have been investigated as antiviral strategies against SARS-CoV-2. This review aims to explore the complex interplay between PRRs and SARS-CoV-2 in depth, considering its implications for prognostic biomarkers, targeted therapeutic strategies and the mechanistic understanding of long LC. Additionally, it outlines future perspectives that could help to address knowledge gaps in PRR-mediated responses during SARS-CoV-2 infection.},
}

@article {pmid41009608,
year = {2025},
author = {Mantle, D and Domingo, JC and Golomb, BA and Castro-Marrero, J},
title = {Gulf War Illness, Fibromyalgia, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Overlap in Common Symptoms and Underlying Biological Mechanisms: Implications for Future Therapeutic Strategies.},
journal = {International journal of molecular sciences},
volume = {26},
number = {18},
pages = {},
doi = {10.3390/ijms26189044},
pmid = {41009608},
issn = {1422-0067},
mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy/metabolism/pathology/drug therapy ; *Persian Gulf Syndrome/therapy/pathology/metabolism ; Ubiquinone/analogs & derivatives/therapeutic use ; *Fibromyalgia/therapy/metabolism/pathology/drug therapy ; *COVID-19/complications/metabolism/therapy ; Oxidative Stress ; SARS-CoV-2 ; },
abstract = {Although Gulf War Illness (GWI), fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID have distinct origins, in this article we have reviewed evidence that these disorders comprise a group of so-called low-energy associated disorders with overlapping common symptoms underlying pathology. In particular, evidence for mitochondrial dysfunction, oxidative stress, inflammation, immune dysregulation, neuroendocrine dysfunction, disrupted brain-gut-microbiome axis, apoptosis/ferroptosis and telomere shortening as common features in the pathogenesis of these disorders has been identified. Given the role of coenzyme Q10 (CoQ10) in promoting normal mitochondrial function, as an antioxidant, antiinflammatory and antiapoptotic and antiferroptotic agent, there is a rationale for supplementary CoQ10 in the management of these disorders. The reported benefits of supplementary CoQ10 administration in GWI, FM, ME/CFS and long COVID have been reviewed; the potential benefit of supplementary CoQ10 in reducing telomere shortening and improving the efficiency of stem cell transfer relevant has also been identified as promising therapeutic strategies in these disorders. This review advances beyond previous systematic reviews and consensus statements on overlapping similar symptoms and underlying biological pathomechanisms in these complex disorders.},
}

Humans
*Fatigue Syndrome, Chronic/therapy/metabolism/pathology/drug therapy
*Persian Gulf Syndrome/therapy/pathology/metabolism
Ubiquinone/analogs & derivatives/therapeutic use
*Fibromyalgia/therapy/metabolism/pathology/drug therapy
*COVID-19/complications/metabolism/therapy
Oxidative Stress
SARS-CoV-2

@article {pmid41008646,
year = {2025},
author = {Lee, E and Ozigbo, AA and Varon, J and Halma, M and Laezzo, M and Ang, SP and Iglesias, J},
title = {Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review.},
journal = {Biomolecules},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/biom15091339},
pmid = {41008646},
issn = {2218-273X},
mesh = {Humans ; *COVID-19/metabolism/complications/pathology ; *Mitochondria/metabolism/pathology ; *Reactive Oxygen Species/metabolism ; SARS-CoV-2/metabolism ; *Spike Glycoprotein, Coronavirus/metabolism ; Post-Acute COVID-19 Syndrome ; Oxidative Stress ; },
abstract = {Post-acute sequelae of SARS-CoV-2 infection (long COVID) present with persistent fatigue, cognitive impairment, and autonomic and multisystem dysfunctions that often go unnoticed by standard diagnostic tests. Increasing evidence suggests that mitochondrial dysfunction and oxidative stress are central drivers of these post-viral sequelae. Viral infections, particularly SARS-CoV-2, disrupt mitochondrial bioenergetics by altering membrane integrity, increasing mitochondrial reactive oxygen species (mtROS), and impairing mitophagy, leading to sustained immune activation and metabolic imbalance. This review synthesizes an understanding of how mitochondrial redox signaling and impaired clearance of damaged mitochondria contribute to chronic inflammation and multisystem organ symptoms in both long COVID and post-vaccine injury. We discuss translational biomarkers and non-invasive techniques, exploring therapeutic strategies that include pharmacological, non-pharmacological, and nutritional approaches, as well as imaging modalities aimed at assessing and restoring mitochondrial health. Recognizing long COVID as a mitochondrial disorder that stems from redox imbalance will open new options for personalized treatment and management guided by biomarkers. Future clinical trials are essential to validate these approaches and translate mitochondrial resuscitation into effective care for patients suffering from long COVID and related post-viral syndromes.},
}

Humans
*COVID-19/metabolism/complications/pathology
*Mitochondria/metabolism/pathology
*Reactive Oxygen Species/metabolism
SARS-CoV-2/metabolism
*Spike Glycoprotein, Coronavirus/metabolism
Post-Acute COVID-19 Syndrome
Oxidative Stress

@article {pmid41007506,
year = {2025},
author = {Kachroo, P and Boivin, G and Cowling, BJ and Shannon, W and Mallefet, P and Kalita, P and Georgescu, AM},
title = {Long COVID Symptom Management Through Self-Care and Nonprescription Treatment Options: A Narrative Review.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {9},
pages = {},
doi = {10.3390/ijerph22091362},
pmid = {41007506},
issn = {1660-4601},
mesh = {Humans ; *COVID-19/therapy/complications ; *Self Care ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {Many patients experience unique or persistent symptoms several months following the onset of infection with severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. While this condition is commonly referred to as long COVID, no universally accepted definition exists; therefore, many patients go underrecognized and underreported. Long COVID can involve almost any major organ system and is characterized by widely heterogeneous persistent or recurrent symptoms including fatigue, headache, cough, dyspnea, chest pain, cognitive dysfunction, anxiety, and depression. In line with the wide array of symptoms, numerous potential underlying pathophysiologic pathways, including viral persistence, prolonged inflammation, autoimmune reactions, endothelial dysfunction, and dysbiosis of the microbiome of the gut, may contribute to the symptomology of long COVID. Therapy is directed at symptomatic control; however, no pharmacologic treatments are specifically approved for the management of symptoms associated with long COVID. Several common symptoms of long COVID may be managed with nonprescription treatments (pharmacologic and nonpharmacologic). The goal of this review is to provide clinicians with a better understanding of long COVID and review the latest recommendations for managing common mild-to-moderate symptoms with nonprescription treatment options.},
}

Humans
*COVID-19/therapy/complications
*Self Care
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid41003635,
year = {2025},
author = {Presta, V and Guarnieri, A and Laurenti, F and Mazzei, S and di Martino, O and Vitale, M and Condello, G},
title = {Post-Acute COVID-19 Syndrome (PACS) and Exercise Interventions: A Systematic Review of Randomized Controlled Trials.},
journal = {Sports (Basel, Switzerland)},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/sports13090329},
pmid = {41003635},
issn = {2075-4663},
support = {MUR_DM737_2022_FIL_PROGETTI_B_CONDELLO_COFIN//Bando di Ateneo per la Ricerca 2022 - Azione B/ ; },
abstract = {The aim of this systematic review (PROSPERO registration number CRD42024517069) was to investigate the effectiveness of exercise interventions in Post-Acute COVID-19 Syndrome (PACS). We searched on several databases and followed the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We included randomized controlled trials that evaluate exercise interventions in adults (40-60 years old) diagnosed with PACS. The outcomes of interest were health-related quality of life (HRQoL) and functional fitness. Twenty studies were included after screening. Thirteen and fourteen studies were rated as "low" risk for HRQoL and functional fitness outcomes, respectively. Based on the evidence, an 8-week exercise protocol of aerobic training in combination with strength-based and breathing exercises was found to be safe and feasible while improving quality of life and functional fitness in people with PACS. Telerehabilitation can also be an option to avoid contagion and physical contact with the same beneficial effects. Future research should expand the knowledge about other types of exercise (i.e., water-based exercises) with high-quality trials and consider whether findings could be potentially transferable to recovery from a wider spectrum of viral infections.},
}

@article {pmid40995517,
year = {2025},
author = {Guo, X and Li, X},
title = {Advances in home-based respiratory muscle training for improving physical function in older adults with long COVID.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1662537},
pmid = {40995517},
issn = {1664-042X},
abstract = {Long COVID imposes a substantial burden on older adults, manifesting as respiratory muscle dysfunction that severely compromises physical function. This narrative review synthesizes current evidence on home-based respiratory muscle training (RMT)-a non-pharmacological intervention targeting this impairment in older patients with long COVID-while critically evaluating its physiological mechanisms, therapeutic efficacy, implementation feasibility, and persistent challenges. Respiratory muscle dysfunction, caused by multifaceted neurophysiological and structural impairments, is a core mechanism of exertional dyspnea and fatigue in older adults, further aggravated by age-related decline. RMT mitigates these effects through improvements in respiratory strength, endurance, ventilatory efficiency, metaboreflex and autonomic regulation, and psychological wellbeing. Home-based RMT demonstrates non-inferior efficacy to conventional programs while providing critical accessibility for mobility-limited older adults. Nevertheless, implementation barriers include challenges in individualizing geriatric-adapted exercise prescriptions, technological access limitations, variable adherence, insufficient clinician training in remote assessment, and regulatory/policy gaps in telerehabilitation frameworks. Despite these challenges, home-based RMT represents a promising strategy for managing debilitating respiratory sequelae in this vulnerable population. This review consolidates RMT's physiological rationale and clinical evidence, underscores its integration potential within collaborative care models, and outlines key translational priorities-including hybrid delivery systems and refined geriatric-specific protocols-to accelerate clinical adoption.},
}

@article {pmid40989546,
year = {2025},
author = {Cruz Neto, J and Fiuza Olivindo, CV and Guimarães Dos Santos, JA and Araujo da Silva, MA and de Oliveira Sales Junior, R},
title = {Cardiometabolic factors related to post-COVID-19 conditions: a scoping review.},
journal = {Revista Cuidarte},
volume = {16},
number = {2},
pages = {e4290},
pmid = {40989546},
issn = {2346-3414},
abstract = {INTRODUCTION: Post-COVID syndrome is a pathology that involves multiple sequelae. It is important to identify cardiometabolic risk factors as a way of preventing complications.

OBJECTIVE: To map the scientific evidence related to cardiometabolic factors in long post-COVID-19 conditions.

MATERIALS AND METHODS: Scoping review with the guiding question: What scientific evidence relates cardiometabolic factors to patients with long post-Covid-19 syndrome? The sources of information used were six databases via the CAPES journal portal. For the gray literature, we used the CAPES catalog of theses and dissertations, the Brazilian Digital Library of Theses and Dissertations, the Who Library Database and the medRxiv and OpenGrey repositories. The following descriptors were used: Adult, heart disease risk factors, Syndrome, SARS-CoV-2 and Covid 19 crossed using the Boolean operators AND and OR.

RESULTS: 14 studies were included. The cardiometabolic factors found were: abnormal levels of triglycerides, glycated hemoglobin, ferritin, inflammatory processes, decreased platelets, phospholipids and endothelial cells, oxidative stress, higher concentrations of monosaccharides and reduced polysaccharides, increased LDL, ALT, AST and bilirubin, with reduced GFR.

DISCUSSION: Patients with long-term COVID report persistent and debilitating symptoms that affect recovery, quality of life, economic and social activities. In addition to increased resting heart rate, tachycardia, palpitations, hypotension, syncope, orthostatic tachycardia, angina and heart attack.

CONCLUSION: Cardiometabolic factors expose the vulnerability of individuals affected by long Covid-19, so strategies are needed to reduce the systemic inflammatory impact of the disease and its clinical consequences.},
}

@article {pmid40981264,
year = {2025},
author = {Pomroy, HJ and Mote, A and Mathew, S and Chanasseril, S and Lu, V and Cheema, AK},
title = {From Fork to Brain: The Role of AGE-RAGE Signaling and the Western Diet in Neurodegenerative Disease.},
journal = {NeuroSci},
volume = {6},
number = {3},
pages = {},
doi = {10.3390/neurosci6030089},
pmid = {40981264},
issn = {2673-4087},
abstract = {Advanced glycation end products (AGEs) are reactive compounds formed through non-enzymatic glycation in a process known as the Maillard reaction. While humans produce AGEs endogenously, these compounds can also enter the body through dietary sources, food preparation methods, and exposure to agricultural and food-related chemicals. AGEs can accumulate within cells and impair cellular function. In addition, when AGEs bind to receptors for advanced glycation end products (RAGE), they activate intracellular signaling pathways that promote the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation. Sustained AGE-RAGE signaling drives chronic inflammation contributing to the development of various ailments, including neurodegenerative diseases. This review examines AGE formation, metabolism, and accumulation, with an emphasis on dietary sources as modifiable contributors to AGE-RAGE mediated pathology. We highlight the need for further research on dietary AGE restriction as a potential strategy to prevent or slow the progression of neurodegenerative and neuroinflammatory disorders.},
}

@article {pmid40980513,
year = {2025},
author = {Pettemeridou, E and Loizidou, M and Trajkovic, J and Constantinou, M and De Smet, S and Baeken, C and Sack, AT and Williams, SCR and Constantinidou, F},
title = {Cognitive and Psychological Symptoms in Post-COVID-19 Condition: A Systematic Review of Structural and Functional Neuroimaging, Neurophysiology, and Intervention Studies.},
journal = {Archives of rehabilitation research and clinical translation},
volume = {7},
number = {3},
pages = {100461},
pmid = {40980513},
issn = {2590-1095},
abstract = {OBJECTIVE: To investigate the structural, functional, and neurophysiological brain changes associated with post-COVID-19 condition (PCC)-related cognitive and psychological issues and evaluate the efficacy of noninvasive brain stimulation (NIBS) and cognitive rehabilitation interventions.

DATA SOURCES: Electronic databases, including Web of Science, PubMed, and Embase, were systematically searched for articles published before February 1, 2025, using terms such as "post-COVID-19 condition," "cognitive dysfunction," "brain changes," "noninvasive brain stimulation," and "cognitive rehabilitation." Language was restricted to English, and only studies involving human participants were included.

STUDY SELECTION: Studies with human participants aged ≥18 years diagnosed with PCC, employing magnetic resonance imaging, functional magnetic resonance imaging, positron emission tomography, and electroencephalography, and interventions such as NIBS and cognitive rehabilitation were included. Articles were selected through independent review by multiple authors, with consensus resolving discrepancies. Of the 123 studies initially identified, 78 met the inclusion criteria.

DATA EXTRACTION: Data on participant demographics, methodologies, neurophysiological changes, and intervention outcomes were extracted by 2 independent reviewers using predefined guidelines. Study quality was assessed using the Newcastle-Ottawa Scale and Critical Appraisal Skills Program tools.

DATA SYNTHESIS: Seventy-eight studies with over 5900 participants met the inclusion criteria. Significant cognitive impairments were observed in attention, executive function, and memory (N=78). Key findings included mixed evidence of gray matter (N=16) and white matter volume changes (N=20), cortical thickness alterations (N=9), variations in functional connectivity (N=14), electrophysiology (N=9), and blood flow (N=8). NIBS, including transcranial magnetic stimulation (N=8) and transcranial direct current stimulation (N=2), showed potential benefits for managing depression and cognitive impairments. Although cognitive rehabilitation (N=3) showed promise, it requires further investigation.

CONCLUSIONS: This review highlights the complex neurologic underpinnings of PCC and the potential of NIBS and cognitive rehabilitation as interventions. Further research is essential to refine these interventions and establish evidence-based strategies for addressing long-term cognitive and psychological effects of PCC.},
}

@article {pmid40975587,
year = {2025},
author = {Sinha, SS and Bari, S and Tripathi, P and Kant, S and Tripathi, SM},
title = {Neuropsychiatric manifestations of long COVID.},
journal = {The Indian journal of tuberculosis},
volume = {72},
number = {4},
pages = {532-536},
doi = {10.1016/j.ijtb.2025.02.020},
pmid = {40975587},
issn = {0019-5707},
mesh = {Humans ; *COVID-19/psychology/complications ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Mental Disorders/etiology ; *Nervous System Diseases/etiology ; },
abstract = {In 2019 after the COVID-19 outbreak, a subset of patients was observed to be experiencing unusual symptoms and prolonged illness following SARS-CoV-2 infection and were labeled as "Long-haulers". Various terms like Long COVID, and Post-COVID-19 Conditions (PCC) were used to describe symptoms extending four weeks or more. Long COVID encompasses a range of persistent symptoms with a multisystemic nature, exhibiting a relapsing-remitting pattern. Various theories explaining Long COVID such as direct neuro-invasion, systemic effects of the virus, and neuroimmune dysregulation have been suggested. Clinical manifestations of Long COVID include diverse symptoms with fatigue, dyspnea, and cognitive impairment being common symptoms reported. Neurological manifestations are more prevalent in severe COVID-19 cases. Non-specific neurological manifestations include loss of taste and smell while specific neurological manifestations include hemiplegia and large artery ischemic stroke. COVID-19 medications may also cause neurological symptoms. Psychiatric manifestations include depression, anxiety, panic disorders, post-traumatic stress disorder (PTSD), psychosis, and cognitive symptoms such as attention and executive function deficits. Psychological symptoms vary among different social groups like frontline health workers, young individuals, and the elderly. Social isolation exerts a substantial impact on the psychological presentations of Long COVID through mechanisms such as Hypothalamic-Pituitary-Adrenal axis (HPA) hyperactivation, epigenetic modifications, increased steroid concentrations, immune system suppression, and reactivation of latent infections. Conclusively, neuroimmune dysregulation, social isolation and associated factors serve as the link between SARS-CoV-2 virus, long COVID and its neuropsychiatric manifestations.},
}

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

@article {pmid40042223,
year = {2025},
author = {Monte, AL and Karla Tavares do Nascimento Faustino da Silva, J and Duarte de Oliveira, M and Quintella Farah, B and Kanegusuku, H and Almeida Correia, M and Mendes Ritti-Dias, R},
title = {Dropouts in Exercise Rehabilitation Program in Patients With Long COVID: A Systematic Review.},
journal = {American journal of physical medicine & rehabilitation},
volume = {104},
number = {10},
pages = {883-889},
pmid = {40042223},
issn = {1537-7385},
mesh = {Humans ; *COVID-19/rehabilitation ; *Patient Dropouts/statistics & numerical data ; *Exercise Therapy ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; },
abstract = {OBJECTIVE: The aim of the study was to describe dropout rates, reasons, and factors associated with dropout during rehabilitation programs for patients with long COVID.

DESIGN: A search was conducted in PubMed, Embase, and Web of Science. Clinical trials were included that involved exercise programs lasting at least 4 weeks and focused on long-COVID patients aged 18 or older of both sexes, reporting on dropouts and their reasons. The TESTEX scale assessed study quality. Data on patients, interventions, and dropout rates were extracted and presented as frequencies.

RESULTS: Twenty-three studies with 1523 patients (mean age 53.0 ± 6.4 yrs, 51% female) were included. Overall, 14% (n = 216) of long-COVID patients dropped out. Reasons included health problems (23%), incomplete assessments (19%), loss of interest (16%), lack of adherence (7%), adherence to other interventions (4%), and 31% unreported. The dropout rate was significantly higher in 2020 compared to 2021 (P = 0.039), while no significant associations were observed between the dropout rate and other variables.

CONCLUSIONS: Exercise rehabilitation studies for long-COVID patients show a 14% dropout rate, with the most common reasons being health-related issues and incomplete assessments.},
}

Humans
*COVID-19/rehabilitation
*Patient Dropouts/statistics & numerical data
*Exercise Therapy
Male
Female
Middle Aged
SARS-CoV-2

@article {pmid40958852,
year = {2025},
author = {Zhu, Y and Quan, P and Yamazaki, T and Norweg, A and Natelson, B and Xu, X},
title = {Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID.},
journal = {Immunometabolism (Cobham, Surrey)},
volume = {7},
number = {4},
pages = {e00068},
pmid = {40958852},
issn = {2633-0407},
abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID are complex, disabling conditions that have emerged as significant public health challenges, affecting millions worldwide. Despite their growing prevalence, effective diagnostics and treatments remain limited, largely due to an incomplete understanding of their underlying pathophysiology. Both conditions share hallmark symptoms of chronic fatigue, cognitive dysfunction, and postexertional malaise, but their biological underpinnings remain to be elucidated. Neuroimaging offers a promising, noninvasive window into the brain's metabolic landscape and has the potential to uncover objective biomarkers for these conditions. In this mini review, we highlight recent advancements in metabolic neuroimaging, particularly positron emission tomography and magnetic resonance imaging/magnetic resonance spectroscopy, that reveal alterations in glucose and oxygen metabolism, neurotransmitter balance, and oxidative stress. These insights point toward shared disruptions in brain energy metabolism and neuroinflammatory processes, which may underlie the persistent symptoms in both ME/CFS and Long-COVID. Importantly, while some findings overlap, inconsistencies in metabolite profiles between ME/CFS and Long-COVID underscore the need for further stratification and longitudinal research. Standardizing definitions, such as identifying Long-COVID patients who meet ME/CFS diagnostic criteria, could help improve study comparability. By summarizing current imaging evidence, this review underscores the potential of neuroimaging to identify imaging biomarkers to advance the clinical diagnosis of Long-COVID and identify therapeutic targets for treatment development. As we continue to face the growing burden of Long-COVID and ME/CFS, metabolic imaging may serve as a powerful tool to bridge gaps in knowledge and accelerate progress toward effective care.},
}

@article {pmid40956375,
year = {2025},
author = {Naushad, Z and Malik, J and Mishra, AK and Singh, S and Shrivastav, D and Sharma, CK and Verma, VV and Pal, RK and Roy, B and Sharma, VK},
title = {Artificial Intelligence in Cardiovascular Health: Insights into Post-COVID Public Health Challenges.},
journal = {High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension},
volume = {},
number = {},
pages = {},
pmid = {40956375},
issn = {1179-1985},
abstract = {Cardiovascular diseases (CVDs) continue to be the topmost cause of the worldwide morbidity and mortality. Risk factors such as diabetes, hypertension, obesity and smoking are significantly worsening the situation. The COVID-19 pandemic has powerfully highlighted the undeniable connection between viral infections and cardiovascular health. Current literature highlights that SARS-CoV-2 contributes to myocardial injury, endothelial dysfunction, thrombosis, and systemic inflammation, increasing the severity of CVD outcomes. Long COVID has also been associated with persistent cardiovascular complications, including myocarditis, arrhythmias, thromboembolic events, and accelerated atherosclerosis. Addressing these challenges requires continued research and public health strategies to mitigate long-term risks. Artificial intelligence (AI) is changing cardiovascular medicine and community health through progressive machine learning (ML) and deep learning (DL) applications. AI enhances risk prediction, facilitates biomarker discovery, and improves imaging techniques such as echocardiography, CT, and MRI for detecting coronary artery disease and myocardial injury on time. Remote monitoring and wearable devices powered by AI enable real-time cardiovascular assessment and personalized treatment. In public health, AI optimizes disease surveillance, epidemiological modeling, and healthcare resource allocation. AI-driven clinical decision support systems improve diagnostic accuracy and health equity by enabling targeted interventions. The integration of AI into cardiovascular medicine and public health offers data-driven, efficient, and patient-centered solutions to mitigate post-COVID cardiovascular complications.},
}

@article {pmid40956349,
year = {2025},
author = {Corrêa-Dias, LC and Lopes-Ribeiro, Á and Mendes, GER and Marques-Ferreira, G and Wilker-Teixeira, C and Clarindo, FA and de Melo Rocha, V and Martuchele-Félix, ME and Retes, HM and Santos, TAP and Azevedo, GLA and Pereira, VEV and de Fátima Silva Moraes, T and de Sousa Reis, EV and Gomes-de-Pontes, L and Rabelo, LF and Dos Santos, EAS and Pereira, CLD and Coelho, FDS and Coelho, RP and Santos, RA and Coelho, GP and da Fonseca, FG and Coelho-Dos-Reis, JGA},
title = {A pain from the nose to the head: neurological commitment during long COVID.},
journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]},
volume = {74},
number = {1},
pages = {127},
pmid = {40956349},
issn = {1420-908X},
mesh = {Humans ; *COVID-19/complications/immunology ; *Neuroinflammatory Diseases/immunology/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long COVID is a debilitating illness with multi-systemic symptoms that affects at least 10% of individuals who have had COVID-19. Symptoms include respiratory, dermatological, gastrointestinal, cardiovascular, and most frequently reported, neurological sequelae. The most common neurological manifestations include fatigue, brain fog, memory issues, attention disorder, and headaches.

METHODS: In this review, we explore the current literature and highlight key findings regarding not only the clinical presentations of neurological commitment during long COVID but mainly the mechanisms that culminate in neuroinflammation, such as autoimmunity, viral reservoirs, and lack of surveillance of T-cells.

RESULTS: Neuroinflammation is a complex multicellular response that directly impacts microglial cells and includes inflammasome activation, trafficking of immune cells, and increased circulating autoantibodies, cytokines, and chemokines in the central nervous system, directly impacting the tissue homeostasis. This review provides important information beyond the clinical manifestations of long COVID. Here, we highlight multifactorial neuroinflammation as the main mechanism involved in long COVID, bringing together several studies that address the different mechanisms that culminate in inflammation of the central nervous system, and highlight possible biomarkers involved in this syndrome and potential therapeutic approaches that have been studied.

CONCLUSION: Thus, this review strengthens research into long COVID and provides new possibilities for future studies.},
}

Humans
*COVID-19/complications/immunology
*Neuroinflammatory Diseases/immunology/etiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid40954187,
year = {2025},
author = {van der Bie, J and Coleon, A and Visser, D and Bogers, WM and den Dunnen, J and Spronk, HMH and Langermans, JAM and Willemen, HLDM and De Melo, GD and Middeldorp, J and Stammes, MA},
title = {Post Pandemic Problem, is there an animal model suitable to investigate PASC.},
journal = {Npj imaging},
volume = {3},
number = {1},
pages = {41},
pmid = {40954187},
issn = {2948-197X},
support = {11080012310002/ZONMW_/ZonMw/Netherlands ; },
abstract = {Although the COVID-19 pandemic is no longer a global health emergency, many patients still suffer from long-term effects, known as post-acute sequelae of COVID-19 (PASC) or long COVID. Understanding its complex pathophysiology requires animal models replicating the post-acute phase, which may aid in developing, the urgently needed, therapeutics. Our review assessed and summarized 81 studies from 1979 manuscripts. In addition, a second table summarizing the imaging findings of 26 studies related to this topic was added, based on a separate literature search of 797 manuscripts. In humans a SARS-CoV-2 infection, the sequelae and possible development of PASC is heterogenic. The same holds true for experimental animal models. While several models are suitable to address different research questions, no single model can fully replicate all aspects of PASC. Imaging plays a crucial role in visualizing these aspects, especially since questionnaires, the primary diagnostic tool in humans, cannot be used in animals. Thus, imaging allows the investigation of pathophysiology in a controlled setting, offering valuable insights. This review summarizes the available animal models and imaging modalities used in PASC research. Our aim is to provide researchers with guidance on selecting the most appropriate model and imaging technique to address their specific research questions.},
}

@article {pmid40944962,
year = {2025},
author = {Yong, SJ and Kenny, TA and Halim, A and Munipalli, B and Alhashem, YN and AlSaihati, H and Al-Subaie, MF and Al Kaabi, NA and Al Fares, MA and Garout, M and Sabour, AA and Alshiekheid, MA and Almansour, ZH and Alotaibi, J and Alrasheed, HA and Alamri, AA and Albayat, H and Alamodi, AS and Tombuloglu, H and Mohapatra, RK and Hazazi, A and Rabaan, AA},
title = {Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options.},
journal = {Reviews in medical virology},
volume = {35},
number = {5},
pages = {e70070},
doi = {10.1002/rmv.70070},
pmid = {40944962},
issn = {1099-1654},
abstract = {With the global rollout of COVID-19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID-like syndrome following vaccination, informally called long Vax and provisionally termed post-COVID-19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies. Our review noted that PCVS typically manifests within days to weeks post-vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small-fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long-term sequelae of myocarditis, vaccine-induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea. We also review pathophysiological hypotheses of PCVS, focussing on the vaccine-derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.},
}

@article {pmid40943770,
year = {2025},
author = {Var, SR and Maeser, N and Blake, J and Zahs, E and Deep, N and Vasilakos, Z and McKay, J and Johnson, S and Strell, P and Chang, A and Korthas, H and Krishna, V and Narayanan, M and Arju, T and Natera-Rodriguez, DE and Roman, A and Schulz, SJ and Shetty, A and Vernekar, M and Waldron, MA and Person, K and Cheeran, M and Li, L and Low, WC},
title = {Pulmonary and Immune Dysfunction in Pediatric Long COVID: A Case Study Evaluating the Utility of ChatGPT-4 for Analyzing Scientific Articles.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
doi = {10.3390/jcm14176011},
pmid = {40943770},
issn = {2077-0383},
support = {AG077772/NH/NIH HHS/United States ; },
abstract = {Coronavirus disease 2019 (COVID-19) in adults is well characterized and associated with multisystem dysfunction. A subset of patients develop post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID), marked by persistent and fluctuating organ system abnormalities. In children, distinct clinical and pathophysiological features of COVID-19 and long COVID are increasingly recognized, though knowledge remains limited relative to adults. The exponential expansion of the COVID-19 literature has made comprehensive appraisal by individual researchers increasingly unfeasible, highlighting the need for new approaches to evidence synthesis. Large language models (LLMs) such as the Generative Pre-trained Transformer (GPT) can process vast amounts of text, offering potential utility in this domain. Earlier versions of GPT, however, have been prone to generating fabricated references or misrepresentations of primary data. To evaluate the potential of more advanced models, we systematically applied GPT-4 to summarize studies on pediatric long COVID published between January 2022 and January 2025. Articles were identified in PubMed, and full-text PDFs were retrieved from publishers. GPT-4-generated summaries were cross-checked against the results sections of the original reports to ensure accuracy before incorporation into a structured review framework. This methodology demonstrates how LLMs may augment traditional literature review by improving efficiency and coverage in rapidly evolving fields, provided that outputs are subjected to rigorous human verification.},
}

@article {pmid40934937,
year = {2025},
author = {Wilhelm, F and Cadamuro, J and Mink, S},
title = {Autoantibodies in long COVID: a systematic review.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00411-6},
pmid = {40934937},
issn = {1474-4457},
abstract = {Post-COVID-19 condition (also known as long COVID) affects a substantial proportion of individuals who have been infected with SARS-CoV-2, profoundly affecting their daily lives and work. Diagnosis and prognosis of long COVID are complex and hindered by heterogeneous symptoms and the absence of validated biomarkers. This systematic review synthesises current evidence on the association between autoantibodies and long COVID, with the goal of evaluating their prognostic and diagnostic utility. Studies published in the PubMed and MEDLINE databases between Jan 1, 2020, and June 10, 2025, were considered. Study selection and quality assessment were done independently by two researchers. Of the 1113 publications screened, 44 studies met the inclusion criteria, with a total of 7571 participants, including 3372 individuals with long COVID. 31 (71%) studies reported an association between autoantibodies and long COVID; however, there was substantial heterogeneity in study design, type and timing of antibody measurements, and long COVID definitions. Several autoantibodies have been associated with long COVID occurrence, symptoms, and severity. Antinuclear antibodies, and autoantibodies targeting G protein-coupled receptors and chemokines, have emerged as potential biomarkers for aiding in the diagnosis, prognosis, and assessment of disease severity in long COVID. However, larger studies are needed to confirm the diagnostic and prognostic utility of these autoantibodies in the context of long COVID.},
}

@article {pmid40930270,
year = {2025},
author = {Walker, TA and Kohler, JZ and Haddad, MM},
title = {Long COVID: Current landscape of neurocognitive sequalae and opportunities to improve care management.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106108},
doi = {10.1016/j.bbi.2025.106108},
pmid = {40930270},
issn = {1090-2139},
}

@article {pmid40922860,
year = {2025},
author = {Potluri, S and Chittiprol, N and Varaganti, V and Avr, V and Vadakedath, S and Arvapally, D and Vemulapalli, C and Begum, GS and Madamsetti, N and Kandi, V},
title = {The Association of SARS-CoV-2 Infection and COVID-19 Vaccination With Sudden Death: An Explorative Review.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e89527},
pmid = {40922860},
issn = {2168-8184},
abstract = {Since its discovery, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become the epicenter of public health concern. This was mainly attributed to the complexity of COVID-19 that resulted in variable disease progression with some developing asymptomatic infections, some suffering mild to moderate infections that resolved without the need for hospitalizations, and a few infected persons developing severe infections that required intensive care unit (ICU) admission and mechanical ventilation. The COVID-19 pandemic spread globally, affecting billions of people and killing millions. Most of the consequences were related to the novelty of the virus, poor understanding of its pathogenesis, and the lack of a specific antiviral drug and vaccine. The vaccines, although manufactured and made available to the public, were approved for emergency use before the completion of human clinical trials. Moreover, the continuous emergence of viruses following mutations resulted in the emergence of viral variants. This has led to doubts over the efficacy of vaccines. Vaccine inequity, represented by the disproportionate availability and distribution of vaccines among the rich and poor, concerns over long-term safety, and hesitancy, affected COVID-19 vaccination, thereby increasing the spread of SARS-CoV-2. Although the COVID-19 pandemic is no longer considered a public health emergency of international concern (PHEIC), the repercussions of the pandemic are still evident in the form of long COVID and post-COVID functional health status (PCFHS), wherein individuals who were previously infected continue to suffer organ dysfunction, primarily affecting the lungs and other organs of the body. During and after the pandemic, COVID-19 and probably vaccination were attributed to the death of many individuals, which were categorized as sudden death (SD) and sudden unnatural death (SUD). It is unclear if these deaths were a result of previous SARS-CoV-2 infection and prior COVID-19 vaccination or both. There are several instances of infected and recovered individuals who were healthy but suddenly developed complications and died. Through this explorative review, we aim to comprehend the role that SARS-CoV-2 infection and/or COVID-19 vaccination play in predisposing people to cardiovascular system (CVS) and central nervous system (CNS) disorders that can result in SD and SUD.},
}

@article {pmid40910058,
year = {2025},
author = {Mazzali, C and Magnoni, P and Zucchi, A and Maifredi, G and Cavalieri d'Oro, L and Gambino, ML and Fanetti, AC and Perotti, PG and Villa, M and Valsecchi, MG and Vigani, D and Lucifora, C and Russo, AG},
title = {Strategies for population-level identification of post-acute sequelae of COVID-19 through health administrative data.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1637112},
pmid = {40910058},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {INTRODUCTION: Post-acute sequelae of COVID-19 (PASC) encompass several clinical outcomes, from new-onset symptoms to both acute and chronic diagnoses, including pulmonary and extrapulmonary manifestations. Health administrative data (HAD) from health information systems allow population-level analyses of such outcomes. Our primary aim was to identify clinical conditions potentially attributable to SARS-CoV-2 infection, and the types of HAD and "diagnostic criteria" used for their detection.

METHODS: We performed a literature review to identify HAD-based cohort studies assessing the association between SARS-CoV-2 infection and medium-/long-term outcomes in the general population. From each included study, we extracted data on design, algorithms used for outcome identification (sources, coding systems, codes, time criteria/thresholds), and whether significant associations with SARS-CoV-2 infection were reported.

RESULTS: We identified six studies investigating acute and chronic conditions grouped by clinical domain (cardiovascular, respiratory, neurologic, mental health, endocrine/metabolic, pediatric, miscellaneous). Two studies also addressed the onset of specific symptoms. Cardio/cerebrovascular conditions were most studied, with significant associations reported for deep vein thrombosis, heart failure, atrial fibrillation, and coronary artery disease. Conditions in other domains were less investigated, with inconsistent findings. Only three studies were designed as test-positive vs. test-negative comparisons.

DISCUSSION: Heterogeneity in data sources, study design, and outcome definitions hinder the comparability of studies and explain the inconsistencies in findings about associations with SARS-CoV-2 infection. Rigorously designed studies on large populations with wide availability of data from health information systems are needed for population-level analyses on PASC, and especially on its impact on chronic diseases and their future burden on healthcare systems.},
}

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

@article {pmid40908304,
year = {2025},
author = {Ivković, V and Anandh, U and Bell, S and Kronbichler, A and Soler, MJ and Bruchfeld, A},
title = {Long COVID and the kidney.},
journal = {Nature reviews. Nephrology},
volume = {},
number = {},
pages = {},
pmid = {40908304},
issn = {1759-507X},
abstract = {Long coronavirus disease (COVID) - commonly defined as symptoms and/or long-term effects that persist for at least 3 months after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cannot be explained by an alternative diagnosis - is a complex, multifaceted and heterogeneous disease that affects many organ systems, including the kidney. COVID-19 can cause acute kidney injury, and several studies have reported an increased risk of chronic kidney disease (CKD) following COVID-19, suggesting that CKD can be a manifestation of long COVID. Furthermore, patients with CKD are at an increased risk of severe COVID-19 and of long COVID. COVID-19 has also been associated with the development of COVID-19-associated nephropathy, which is a collapsing form of focal segmental glomerulosclerosis, and an increased incidence of new-onset vasculitis. Some early reports described associations of COVID-19 and/or SARS-CoV-2 vaccines with relapse or new-onset of other glomerular diseases, but this link was not confirmed in large population-based studies. SARS-CoV-2 vaccination reduces the risk of COVID-19 and long COVID and is particularly important for protecting vulnerable populations such as patients with CKD. Structured long-term follow-up of patients with COVID-19 and post-infectious sequelae is needed to provide further insight into the trajectory of long COVID and enable identification of those at risk of CKD.},
}

@article {pmid40904575,
year = {2025},
author = {Shen, S and Zhao, X and Pei, J and Wang, B and Hou, J and Chai, R and Guo, Y and Li, F and Hao, J and Wu, Z},
title = {Exploring the psychological impact of long COVID: symptoms, mechanisms, and treatments.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1555370},
pmid = {40904575},
issn = {1664-0640},
abstract = {Long COVID (LC) refers to a multisystem condition that persists after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). In addition to physical symptoms, the psychological impact is particularly pronounced. This review summarizes the manifestations, potential mechanisms, epidemiological characteristics, and current interventions related to psychological disorders in LC. Drawing on domestic and international literature, it highlights anxiety, depression, cognitive dysfunction, and post-traumatic stress disorder (PTSD) as the primary psychological symptoms. These symptoms may be associated with neuroinflammation, immune abnormalities, vascular dysfunction, and psychosocial stress. Although research in this area is still developing, psychotherapy, pharmacotherapy, neuromodulation, and lifestyle interventions show promise as treatment approaches. This review aims to provide insights that can inform future research on clinical treatments and psychological care for individuals with LC.},
}

@article {pmid40802287,
year = {2025},
author = {Coughtrey, A and Pereira, SMP and Ladhani, S and Shafran, R and Stephenson, T},
title = {Long COVID in children and young people: then and now.},
journal = {Current opinion in infectious diseases},
volume = {38},
number = {5},
pages = {487-492},
pmid = {40802287},
issn = {1473-6527},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology ; Child ; Adolescent ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Fatigue ; Young Adult ; },
abstract = {PURPOSE OF REVIEW: On 11 March 2020, the WHO characterized COVID-19 as a pandemic. A clinical case definition for post-COVID-19 condition in children and adolescents by expert consensus was agreed by the WHO in 2023. It is now 5 years since the WHO declared a pandemic, and this review aims to summarize key advances in our understanding of long COVID over those 5 years.

RECENT FINDINGS: That symptoms could persist in adults and CYP for months after initial infection was first reported in Autumn 2020. Long COVID in adults is frequently characterized by symptoms of fatigue and breathlessness but brain-fog, joint and muscle pain have been reported much more commonly in adult follow-up than CYP. The most common persisting symptoms experienced by CYP after COVID-19 infection in initial studies, often with less than a year of follow-up, were fatigue, headache, shortness of breath and persisting loss of smell and taste. With longer follow-up, up to 2 years, the commonest symptoms still include not only fatigue, headache and shortness of breath but also sleep difficulties, whereas loss of smell and taste persisted only in a minority. However, many symptoms were almost as common in test-negative controls, raising questions about the causal role of SARS-CoV-2 virus. Predictors of long COVID, as defined, were female sex, history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems.

SUMMARY: The implications of the findings for clinical practice and research are that long COVID is not the same in CYP as adults; both their physical and mental health should be studied; and intervention trials are needed.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology
Child
Adolescent
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Fatigue
Young Adult

@article {pmid40748012,
year = {2025},
author = {Waxse, BJ and Rao, S},
title = {Data science for pediatric infectious disease: utilizing COVID-19 as a model.},
journal = {Current opinion in infectious diseases},
volume = {38},
number = {5},
pages = {493-498},
doi = {10.1097/QCO.0000000000001139},
pmid = {40748012},
issn = {1473-6527},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; Child ; *Data Science/methods ; SARS-CoV-2 ; Pediatrics ; Pandemics ; Public Health ; },
abstract = {PURPOSE OF REVIEW: During the COVID-19 pandemic, governments and public health agencies used data science tools and data sources in real time to evaluate pathogen transmissibility, disease burden, healthcare capacity, and evaluate treatment and preventive measures. The purpose of the review is to highlight the application of these data sources and methods during the COVID-19 response.

RECENT FINDINGS: Advances in the development of common data models enabled multisite data networks to overcome healthcare data fragmentation, enabling national surveillance platforms, and offering unprecedented statistical power to conduct national surveillance and detect emerging clinical entities like MIS-C and long COVID in diverse pediatric populations. These integrated networks were also used in evaluating the effectiveness of vaccines and therapies. New surveillance approaches combining traditional clinical data with novel data sources including wastewater detection, web-based search engines, and mobility patterns yielded comprehensive ensemble approaches that informed public health policy.

SUMMARY: The COVID-19 pandemic highlighted the importance of timely evidence for decision-making during outbreak responses and the benefits of using data science tools to help provide real time, actionable insights, which can help guide our public health response to infectious diseases threats in the future.},
}

Humans
*COVID-19/epidemiology/prevention & control
Child
*Data Science/methods
SARS-CoV-2
Pediatrics
Pandemics
Public Health

@article {pmid40536011,
year = {2025},
author = {Moen, JK and Baker, CA and Iwasaki, A},
title = {Neuroimmune pathophysiology of long COVID.},
journal = {Psychiatry and clinical neurosciences},
volume = {79},
number = {9},
pages = {514-530},
pmid = {40536011},
issn = {1440-1819},
support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 AI157488/AI/NIAID NIH HHS/United States ; R01AI157488//National Institute of Allergy and Infectious Diseases/ ; N/A/HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {Humans ; *COVID-19/immunology/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; *Neuroimmunomodulation/physiology ; *Nervous System Diseases/immunology/physiopathology/etiology ; SARS-CoV-2 ; Animals ; *Peripheral Nervous System Diseases/immunology/physiopathology/etiology ; Fatigue/physiopathology/immunology ; },
abstract = {Although COVID-19 was originally considered a respiratory illness, it is now well established that SARS-CoV-2 infection can have far-reaching impacts on the nervous system. Neurological symptoms such as chemosensory dysfunction are frequently observed during acute infection and approximately 10% of COVID-19 cases will go on to develop new or persistent long-term symptoms, a condition known in the literature as post-acute symptoms of COVID-19 (PASC) or by the patient-coined term Long COVID. Common neurological symptoms in Long COVID include new onset cognitive difficulties, dysautonomia, fatigue, and peripheral neuropathy. The emergence of Long COVID has prompted renewed interest in the study of post-acute infection syndromes (PAIS), particularly in the area of neuroimmune interactions. In this review we provide a comprehensive overview of the current body of literature on neurological manifestations of SARS-CoV-2 infection and Long COVID, with an emphasis on neuroimmune mechanisms drawn largely from autopsy studies and animal models. A more complete understanding of neuroimmune crosstalk in Long COVID will not only guide the development of therapies for this highly disabling condition but will also contribute to our general understanding of neuroimmune interactions in health and disease.},
}

Humans
*COVID-19/immunology/complications/physiopathology
Post-Acute COVID-19 Syndrome
*Neuroimmunomodulation/physiology
*Nervous System Diseases/immunology/physiopathology/etiology
SARS-CoV-2
Animals
*Peripheral Nervous System Diseases/immunology/physiopathology/etiology
Fatigue/physiopathology/immunology

@article {pmid40883647,
year = {2025},
author = {Fayyad-Kazan, M},
title = {MicroRNAs in SARS-CoV-2 infection: emerging modulators of inflammation, pathogenesis, and therapeutic potential.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {40883647},
issn = {1568-5608},
abstract = {Since the onset of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), elucidating the molecular regulators of viral pathogenesis and host response has been a critical international research objective. Among these, microRNAs (miRNAs), small non-coding RNAs, that modulate gene expression post-transcriptionally-have emerged as central orchestrators of host-virus interactions. This review exhaustively examines the roles of host-derived miRNAs in SARS-CoV-2 infection, including their roles in viral entry, replication, immune evasion, inflammation, and tissue injury. Dysregulation of certain miRNAs, such as miR-155, miR-146a, and miR-21, has been implicated in disease severity, comorbidities (such as diabetes, obesity), neurological complications, and pregnancy complications. In long COVID (PASC), chronic miRNA changes are linked to persistent inflammation, fibrosis, and cardiometabolic impairment. We emphasize current breakthroughs in miRNA research, including machine learning algorithms for miRNA-based disease stratification, CRISPR-engineered miRNA modulation, exosomal miRNA delivery platforms, and miRNA-adjuvanted vaccines. These advances highlight the potential of miRNAs as diagnostic biomarkers and therapeutic targets. Nevertheless, shortcomings persist in clinical validation, delivery optimization, and tissue-specific miRNA function elucidation. These gaps must be addressed to involve miRNAs in controlling current and future viral infections. This review consolidated differentially expressed miRNAs across disease stages, comorbidities, and clinical settings, providing a valuable resource for translational research and therapeutic innovation.},
}

@article {pmid40875678,
year = {2025},
author = {Schapowal, A},
title = {[Long COVID, Post-COVID-Syndrom: Langzeitfolgen von SARS-CoV-2-Infektionen und Nutzen von Ginkgo biloba].},
journal = {Complementary medicine research},
volume = {},
number = {},
pages = {1-8},
doi = {10.1159/000548075},
pmid = {40875678},
issn = {2504-2106},
abstract = {Background Long COVID and Post-COVID Syndrome are long-term consequences of SARS-CoV-2 infections, causing a range of physical, cognitive, and psychological symptoms such as fatigue, shortness of breath, memory impairment, and sleep disturbances. The exact pathophysiology remains unclear but is thought to involve persistent viral particles, microvascular dysfunction, autoimmune reactions, and autonomic nervous system dysregulation. Summary Diagnosing Long COVID is challenging due to the lack of standardized tests. A multimodal treatment approach is recommended, incorporating symptomatic medication, physiotherapy, psychotherapy, as well as nutritional and exercise therapy. One promising complementary therapeutic option is the use of standardized Ginkgo biloba extracts. Their antioxidant, anti-inflammatory, and neuroprotective properties may help alleviate cognitive impairments, fatigue, and cardiovascular symptoms. Initial studies and case reports suggest positive effects, but further clinical trials are necessary to confirm efficacy. Key Messages Long COVID and Post-COVID Syndrome affect multiple organ systems and significantly reduce quality of life. Diagnosis remains difficult due to the absence of specific tests. A multimodal therapy approach is currently the most promising strategy. Standardized Ginkgo biloba extracts show potential benefits for neurocognitive and cardiovascular symptoms in early studies.},
}

@article {pmid40872911,
year = {2025},
author = {Zambrano-Sánchez, G and Rivadeneira, J and Manterola, C and Otzen, T and Fuenmayor-González, L},
title = {Immunization as Protection Against Long COVID in the Americas: A Scoping Review.},
journal = {Vaccines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/vaccines13080822},
pmid = {40872911},
issn = {2076-393X},
support = {Folio (85220114).//ANID + SUBVENCIÓN A INSTALACIÓN EN LA ACADEMIA CONVOCATORIA AÑO 2022/ ; },
abstract = {INTRODUCTION: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic's impact, there is a lack of evidence of its efficacy in preventing long COVID in the region.

METHODS: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables.

RESULTS: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies.

CONCLUSIONS: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes.},
}

@article {pmid40872813,
year = {2025},
author = {Muthiah, D and Vaddadi, K and Liu, L},
title = {Breathless Aftermath: Post-COVID-19 Pulmonary Fibrosis.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/v17081098},
pmid = {40872813},
issn = {1999-4915},
support = {R01HL157450, R21AI189861 and P30GM149368//National Institutes of Health grants, Oklahoma Center for Adult Stem Cell Research and the Lundberg-Kienlen Endowment fund (to LL)/ ; },
mesh = {Humans ; *COVID-19/complications ; *Pulmonary Fibrosis/etiology/epidemiology/diagnosis/therapy/pathology/virology ; SARS-CoV-2 ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {A significant number of individuals recovering from COVID-19 continue to experience persistent symptoms, collectively referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or long COVID. Among these complications, post-COVID-19 pulmonary fibrosis (PC19-PF) is one of the most severe long-term outcomes, characterized by progressive lung scarring, chronic respiratory impairment, and reduced quality of life. Despite the increasing prevalence of PC19-PF, its underlying mechanisms remain poorly understood. In this review, we provide a comprehensive overview of PC19-PF, including its epidemiology, clinical manifestations, diagnostic strategies, and mechanistic insights. Additionally, we highlight the shared pathways between PC19-PF and other fibrotic lung diseases and discuss emerging therapeutic strategies. This review consolidates emerging insights from both clinical and experimental studies to advance our understanding of PC19-PF pathogenesis and guide the development of mechanism-based therapeutic approaches.},
}

Humans
*COVID-19/complications
*Pulmonary Fibrosis/etiology/epidemiology/diagnosis/therapy/pathology/virology
SARS-CoV-2
Lung/pathology/virology
Post-Acute COVID-19 Syndrome
Quality of Life

@article {pmid40872762,
year = {2025},
author = {Cao, Y and Wang, Y and Huang, D and Tan, YJ},
title = {The Role of SARS-CoV-2 Nucleocapsid Protein in Host Inflammation.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
doi = {10.3390/v17081046},
pmid = {40872762},
issn = {1999-4915},
support = {T2EP30121-0012//Ministry of Education/ ; },
mesh = {Humans ; *Coronavirus Nucleocapsid Proteins/immunology/metabolism ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology ; *Inflammation/immunology/virology ; *Phosphoproteins/immunology/metabolism ; Host-Pathogen Interactions ; Animals ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has posed substantial health threats and triggered widespread global economic disruption. The nucleocapsid (N) protein of SARS-CoV-2 is not only a key structural protein but also instrumental in mediating the host immune response, contributing significantly to inflammation and viral pathogenesis. Due to its immunogenic properties, SARS-CoV-2 N protein also interacts with host factors associated with various pre-existing inflammatory conditions and may possibly contribute to the long-term symptoms suffered by some COVID-19 patients after recovery-known as long COVID. This review provides a comprehensive overview of recent advances in elucidating the biological functions of the N protein. In particular, it highlights the mechanisms by which the N protein contributes to host inflammatory responses and elaborates on its association with long COVID and pre-existing inflammatory disorders.},
}

Humans
*Coronavirus Nucleocapsid Proteins/immunology/metabolism
*COVID-19/immunology/virology
*SARS-CoV-2/immunology
*Inflammation/immunology/virology
*Phosphoproteins/immunology/metabolism
Host-Pathogen Interactions
Animals

@article {pmid40869200,
year = {2025},
author = {Lesgards, JF and Cerdan, D and Perronne, C},
title = {Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167879},
pmid = {40869200},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/immunology/prevention & control/physiopathology ; *COVID-19 Vaccines/adverse effects/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology/metabolism ; Post-Acute COVID-19 Syndrome ; },
abstract = {COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin-angiotensin-aldosterone system (RAAS), the kininogen-kinin-kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects.},
}

Humans
*COVID-19/immunology/prevention & control/physiopathology
*COVID-19 Vaccines/adverse effects/immunology
SARS-CoV-2/immunology
Spike Glycoprotein, Coronavirus/immunology/metabolism
Post-Acute COVID-19 Syndrome

@article {pmid40868989,
year = {2025},
author = {Cimmino, G and D'Elia, S and Morello, M and Titolo, G and Luisi, E and Solimene, A and Serpico, C and Conte, S and Natale, F and Loffredo, FS and Bianco, A and Golino, P},
title = {Cardio-Pulmonary Features of Long COVID: From Molecular and Histopathological Characteristics to Clinical Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
doi = {10.3390/ijms26167668},
pmid = {40868989},
issn = {1422-0067},
mesh = {Humans ; *COVID-19/complications/pathology ; SARS-CoV-2 ; *Cardiovascular Diseases/etiology/pathology ; Lung/pathology/virology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu-characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)-and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals.},
}

Humans
*COVID-19/complications/pathology
SARS-CoV-2
*Cardiovascular Diseases/etiology/pathology
Lung/pathology/virology
Post-Acute COVID-19 Syndrome

@article {pmid40868961,
year = {2025},
author = {Florea, CE and Bălaș-Maftei, B and Rotaru, A and Abudanii, PL and Vieru, ST and Grigoriu, M and Stoian, A and Manciuc, C},
title = {Multiorgan Involvement and Particularly Liver Injury in Long COVID: A Narrative Review.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/life15081314},
pmid = {40868961},
issn = {2075-1729},
abstract = {Since the start of the COVID-19 pandemic, increasing evidence has shown that SARS-CoV-2 infection can cause long-term symptoms, collectively known as long COVID, and that patients with mild COVID-19 can also be affected by persistent fatigue, cognitive impairment, dyspnea, muscle pain, etc. Recent research has also found multiple organ systems, including the liver, to be significant sites of ongoing injury. This narrative review summarizes current knowledge on organ involvement during and after COVID-19, with particular focus on early and delayed hepatic manifestations and associated risk factors. Pathogenesis appears to be multifactorial, involving direct virus action, the body's immune-mediated inflammatory response, microvascular damage, drug-induced hepatotoxicity, and, in some cases, reactivation or exacerbation of pre-existing liver conditions. The hepatic clinical manifestations range from asymptomatic elevations of transaminases to cholangiopathy and even fibrosis. These can persist or progress for months after the initial infection with SARS-CoV-2 is resolved, requiring prolonged monitoring and interdisciplinary care, especially in the presence of metabolic disorders, obesity, or hepatitis. Neurological, cardiovascular, and other sequelae are discussed in parallel, with attention paid to common inflammatory and thrombotic pathways. This review concludes that liver dysfunction is of particular interest in long-COVID due to the liver's central role in metabolism and inflammation. While further research is being conducted into organ-specific and systemic interactions, the available evidence makes a compelling case for extended monitoring and integrated management strategies post infection.},
}

@article {pmid40868058,
year = {2025},
author = {Gonzaga, A and Martinez-Navarrete, G and Macia, L and Anton-Bonete, M and Cahuana, G and Tejedo, JR and Zorrilla-Muñoz, V and Fernandez-Jover, E and Andreu, E and Eguizabal, C and Pérez-Martínez, A and Solano, C and Hernández-Blasco, LM and Soria, B},
title = {Non-Viral Therapy in COVID-19: Where Are We Standing? How Our Experience with COVID May Help Us Develop Cell Therapies for Long COVID Patients.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
doi = {10.3390/biomedicines13081801},
pmid = {40868058},
issn = {2227-9059},
support = {ICI21/00016//Instituto de Salud Carlos III/ ; AVI-GVA-COVID19-068//Valencian Agency of Innovation(AVI)/ ; GVA-COVID19/2021-047//Valencian Agency of Innovation(AVI)/ ; NA//Al-Andalus Biopharma SL/ ; },
abstract = {Objectives: COVID-19, caused by the SARS-CoV-2 virus, has infected over 777 million individuals and led to approximately 7 million deaths worldwide. Despite significant efforts to develop effective therapies, treatment remains largely supportive, especially for severe complications like acute respiratory distress syndrome (ARDS). Numerous compounds from diverse pharmacological classes are currently undergoing preclinical and clinical evaluation, targeting both the virus and the host immune response. Methods: Despite the large number of articles published and after a preliminary attempt was published, we discarded the option of a systematic review. Instead, we have done a description of therapies with these results and a tentative mechanism of action. Results: Preliminary studies and early-phase clinical trials have demonstrated the potential of Mesenchymal Stem Cells (MSCs) in mitigating severe lung damage in COVID-19 patients. Previous research has shown MSCs to be effective in treating various pulmonary conditions, including acute lung injury, idiopathic pulmonary fibrosis, ARDS, asthma, chronic obstructive pulmonary disease, and lung cancer. Their ability to reduce inflammation and promote tissue repair supports their potential role in managing COVID-19-related complications. This review demonstrates the utility of MSCs in the acute phase of COVID-19 and postulates the etiopathogenic role of mitochondria in Long-COVID. Even more, their combination with other therapies is also analyzed. Conclusions: While the therapeutic application of MSCs in COVID-19 is still in early stages, emerging evidence suggests promising outcomes. As research advances, MSCs may become an integral part of treatment strategies for severe COVID-19, particularly in addressing immune-related lung injury and promoting recovery. However, a full pathogenic mechanism may explain or unify the complexity of signs and symptoms of Long COVID and Post-Acute Sequelae (PASC).},
}

@article {pmid40867811,
year = {2025},
author = {Villegas Sánchez, V and Chávez Pacheco, JL and Palacios Arreola, MI and Sierra-Vargas, MP and Colín Godinez, LA and Ahumada Topete, VH and Fernández Plata, R and Higuera-Iglesias, A and Lara-Lemus, R and Aquino-Gálvez, A and Torres-Espíndola, LM and Castillejos-López, M},
title = {A Systematic Review of Genetic Variants in Glutathione S-Transferase Genes and Their Dual Role in SARS-CoV-2 Pathogenesis: From Acute Respiratory Complications to Long COVID.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/antiox14080912},
pmid = {40867811},
issn = {2076-3921},
abstract = {Oxidative stress (OS) occurs when there is an imbalance between oxidants and antioxidants, leading to disruptions in cellular signaling and causing damage to molecules. Glutathione S-transferase (GST) enzymes are crucial for maintaining redox balance by facilitating glutathione conjugation. Increased oxidative damage has been noted during the COVID-19 pandemic, and its persistence may be linked to the onset of long COVID. This systematic review aimed to assess the relationship between GST gene polymorphisms and the prognosis of COVID-19, including long COVID. Adhering to the PRISMA guidelines, a thorough search was carried out in MEDLINE, CENTRAL, PubMed, and EMBASE for studies published from September 2020 to February 2025. Out of an initial selection of 462 articles, ten studies (four concerning COVID-19 severity and six related to long COVID) satisfied the inclusion criteria. The findings regarding GST polymorphisms were not consistent, especially concerning the GSTM1 and GSTT1 isoforms. Nevertheless, evidence indicates a sustained state of oxidative stress in patients with long COVID. The majority of research has focused on cytosolic GSTs, while the functions of microsomal and mitochondrial GST families remain largely unexplored. These findings suggest that further research into the various GST subfamilies and their genetic variants is necessary to enhance our understanding of their impact on COVID-19 severity and the pathophysiology of long COVID.},
}

@article {pmid40866305,
year = {2025},
author = {Bombardieri, AM and Denoue, CF},
title = {Cervical sympathetic block to treat Long COVID: a scoping review.},
journal = {Regional anesthesia and pain medicine},
volume = {},
number = {},
pages = {},
doi = {10.1136/rapm-2025-106879},
pmid = {40866305},
issn = {1532-8651},
abstract = {BACKGROUND: Long COVID is a complex and poorly understood condition characterized by persistent symptoms such as autonomic dysfunction, fatigue, neurocognitive impairment, and olfactory disturbances. Current treatments offer limited and inconsistent benefits. Dysregulation of the sympathetic nervous system is increasingly recognized as a contributor to Long COVID pathophysiology. Cervical sympathetic block (CSB), a procedure that modulates sympathetic tone, has emerged as a potential therapeutic approach.

OBJECTIVE: To review the existing literature on CSB, for Long COVID, focusing on symptom outcomes, proposed mechanisms, and procedural considerations.

EVIDENCE REVIEW: A structured literature search across PubMed, Embase, Scopus, and Web of Science identified studies published between 2022 and March 2025 reporting on CSB in adults with Long COVID. Eligible articles included case reports, case series, observational studies, and one randomized controlled trial evaluating symptom outcomes after the procedure.

FINDINGS: Sixteen studies involving 224 patients were included. Most reported improvement in fatigue, brain fog, and autonomic symptoms, including reduced heart rate and enhanced orthostatic tolerance. Cognitive and psychiatric symptoms such as memory impairment, anxiety, and depression showed variable improvement. Olfactory recovery was inconsistent and appeared to depend on symptom severity. Symptom relief was observed after both unilateral and bilateral blocks, with some responses lasting up to 1 year. No serious complications were reported.

CONCLUSIONS: CSB may offer symptom relief in Long COVID, particularly for fatigue, brain fog, and dysautonomia. However, the evidence remains preliminary and limited by small sample sizes and methodological heterogeneity. Controlled trials are needed to establish efficacy and patient selection criteria.},
}

@article {pmid40857408,
year = {2025},
author = {Bayarri-Olmos, R and Bain, W and Iwasaki, A},
title = {The role of complement in long COVID pathogenesis.},
journal = {JCI insight},
volume = {10},
number = {16},
pages = {},
doi = {10.1172/jci.insight.194314},
pmid = {40857408},
issn = {2379-3708},
mesh = {Humans ; *COVID-19/immunology/complications ; *Complement System Proteins/immunology ; SARS-CoV-2/immunology ; Immunity, Innate/immunology ; Inflammation/immunology ; Complement Activation ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID is a debilitating condition that can develop after a SARS-CoV-2 infection and is characterized by a wide range of chronic symptoms, including weakness, neurocognitive impairment, malaise, fatigue, and many others, that affect multiple organ systems. At least 10% of individuals with a previous infection may develop long COVID, which affects their ability to perform daily functions and work. Despite its severity and widespread impact, this multisystemic condition remains poorly understood. Recent studies suggest that dysregulation of the complement system, a key component of the innate immune response, may contribute to the pathogenesis of long COVID, particularly in connection with coagulation, inflammation, and vascular injury. In this Review, we examine the evidence linking complement system dysregulation to long COVID and explore its potential role in driving disease pathology.},
}

Humans
*COVID-19/immunology/complications
*Complement System Proteins/immunology
SARS-CoV-2/immunology
Immunity, Innate/immunology
Inflammation/immunology
Complement Activation
Post-Acute COVID-19 Syndrome

@article {pmid40801614,
year = {2025},
author = {Sonkodi, B},
title = {Underlying Piezo2 Channelopathy-Induced Neural Switch of COVID-19 Infection.},
journal = {Cells},
volume = {14},
number = {15},
pages = {},
pmid = {40801614},
issn = {2073-4409},
mesh = {Humans ; *COVID-19/metabolism ; *Ion Channels/metabolism ; SARS-CoV-2 ; Neurons/metabolism/pathology ; *Channelopathies/metabolism ; Pandemics ; Animals ; },
abstract = {The focal "hot spot" neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain-body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell-cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection.},
}

Humans
*COVID-19/metabolism
*Ion Channels/metabolism
SARS-CoV-2
Neurons/metabolism/pathology
*Channelopathies/metabolism
Pandemics
Animals

@article {pmid40801304,
year = {2025},
author = {Ellen, A},
title = {From Stagnation to Strategy: Challenges in Advancing Long COVID Research.},
journal = {Journal of evaluation in clinical practice},
volume = {31},
number = {5},
pages = {e70180},
pmid = {40801304},
issn = {1365-2753},
mesh = {Humans ; *COVID-19/physiopathology/complications/epidemiology/therapy ; *Biomedical Research/organization & administration ; SARS-CoV-2 ; Comorbidity ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long COVID is a debilitating multisystemic condition and is a major public health burden, yet the pathophysiology remains poorly understood and there are no effective treatments. Despite the urgent need for better management strategies, research into long COVID is losing momentum.

OBJECTIVES: To help tackle this loss of momentum, this article analyses the major challenges impeding progress and proposes innovative strategies to navigate them and to reinvigorate this research field.

METHOD: The analysis of the long COVID research domain drew on a broad range of scientific literature to identify major barriers to research and potential pathways forward.

RESULTS: The research highlighted critical obstacles, including the lack of reliable biomarkers which has necessitated a reliance on symptom reporting that is inherently heterogenous, temporally complex and often confounded by symptoms arising from pre-existing comorbidities. The absence of pre-infection baseline data further complicates the distinction between long COVID-specific pathophysiology and the effects of pre-existing co-morbidities. Additionally, the long COVID patient population has heterogenous multiorgan pathology, and this diversity makes it difficult to identify and interpret clinical findings.

CONCLUSION: Addressing these methodological and conceptual challenges is essential to accelerate the understanding of long COVID pathophysiology and guide the development of effective interventions.},
}

Humans
*COVID-19/physiopathology/complications/epidemiology/therapy
*Biomedical Research/organization & administration
SARS-CoV-2
Comorbidity
Post-Acute COVID-19 Syndrome

@article {pmid40622467,
year = {2025},
author = {Chatterjee, D and Maparu, K},
title = {Long COVID syndrome: exploring therapies for managing and overcoming persistent symptoms.},
journal = {Inflammopharmacology},
volume = {33},
number = {7},
pages = {4097-4113},
pmid = {40622467},
issn = {1568-5608},
mesh = {Humans ; *COVID-19/therapy/complications/epidemiology/physiopathology ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; SARS-CoV-2 ; Risk Factors ; },
abstract = {Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is a growing global health concern, affecting 10-35% of COVID-19 survivors. Characterized by persistent multisystem symptoms lasting beyond 12 weeks, common manifestations include fatigue, dyspnea, chest pain, cognitive impairment, depression, and anxiety. The underlying pathophysiology remains unclear but is likely to involve immune dysregulation, persistent inflammation, endothelial dysfunction, gut dysbiosis, and viral persistence. This review examines the epidemiology, risk factors, and clinical manifestations of long COVID, with a focus on its impact on cardiopulmonary, neurological, and mental health. Therapeutic approaches include pharmacological interventions such as anti-inflammatory agents, antioxidants, neuroprotective drugs, and repurposed medications. Non-pharmacological strategies, such as physical rehabilitation, cognitive therapy, dietary modification, and emerging therapies like stem cell therapy, as well as immunomodulatory approaches, offer promising avenues for recovery. We also highlight ongoing clinical trials evaluating targeted therapies for long-term COVID syndrome. Future research should focus on elucidating the pathophysiological mechanisms, identifying biomarkers, and optimizing personalized treatment strategies for long-term COVID-19 management.},
}

Humans
*COVID-19/therapy/complications/epidemiology/physiopathology
Post-Acute COVID-19 Syndrome
COVID-19 Drug Treatment
SARS-CoV-2
Risk Factors

@article {pmid35272262,
year = {2022},
author = {Soril, LJJ and Damant, RW and Lam, GY and Smith, MP and Weatherald, J and Bourbeau, J and Hernandez, P and Stickland, MK},
title = {The effectiveness of pulmonary rehabilitation for Post-COVID symptoms: A rapid review of the literature.},
journal = {Respiratory medicine},
volume = {195},
number = {},
pages = {106782},
pmid = {35272262},
issn = {1532-3064},
mesh = {Humans ; *COVID-19/rehabilitation/complications/physiopathology ; Post-Acute COVID-19 Syndrome ; Quality of Life ; SARS-CoV-2 ; Treatment Outcome ; Exercise Tolerance ; },
abstract = {BACKGROUND: Multi-disciplinary rehabilitation is recommended for individuals with post-acute sequelae of COVID-19 infection (i.e., symptoms 3-4 weeks after acute infection). There are emerging reports of use of pulmonary rehabilitation (PR) in the post-acute stages of COVID-19, however the appropriateness of PR for managing post-COVID symptoms remains unclear. To offer practical guidance with regards to post-COVID PR, a greater understanding of the clinical effectiveness literature is required.

METHODS: A rapid review of the published literature was completed. An electronic database search of the literature published between July 1, 2020 and June 1, 2021 was performed in MEDLINE, Pubmed, and EMBASE. Primary studies evaluating the clinical effectiveness of PR for individuals with post-COVID symptoms were included.

RESULTS: Nine studies evaluating the effectiveness of PR were identified; most were small, experimental or quasi-experimental studies, including 1 RCT, and were primarily of low quality. After attending PR, all studies reported improvements in exercise capacity, pulmonary function, and/or quality of life for individuals with post-COVID symptoms who had been hospitalized for their acute COVID-19 infection. Few studies evaluated changes in post-COVID symptom severity or frequency and, of these, improvements in dyspnea, fatigue, anxiety and depression were observed following PR. Further, no studies evaluated non-hospitalized patients or long-term outcomes beyond 3 months after initiating PR.

CONCLUSIONS: With limited high-quality evidence, any recommendations or practical guidance for PR programmes for those with post-COVID symptoms should consider factors such as feasibility, current PR capacity, and resource constraints.},
}

Humans
*COVID-19/rehabilitation/complications/physiopathology
Post-Acute COVID-19 Syndrome
Quality of Life
SARS-CoV-2
Treatment Outcome
Exercise Tolerance

@article {pmid40809128,
year = {2024},
author = {Sun, J and Aikawa, M and Ashktorab, H and Beckmann, ND and Enger, ML and Espinosa, JM and Gai, X and Horne, BD and Keim, P and Lasky-Su, J and Letts, R and Maier, CL and Mandal, M and Nichols, L and Roan, NR and Russell, MW and Rutter, J and Saade, GR and Sharma, K and Shiau, S and Thibodeau, SN and Yang, S and Miele, L and , },
title = {A multi-omics strategy to understand PASC through the RECOVER cohorts: a paradigm for a systems biology approach to the study of chronic conditions.},
journal = {Frontiers in systems biology},
volume = {4},
number = {},
pages = {1422384},
pmid = {40809128},
issn = {2674-0702},
abstract = {Post-Acute Sequelae of SARS-CoV-2 infection (PASC or "Long COVID"), includes numerous chronic conditions associated with widespread morbidity and rising healthcare costs. PASC has highly variable clinical presentations, and likely includes multiple molecular subtypes, but it remains poorly understood from a molecular and mechanistic standpoint. This hampers the development of rationally targeted therapeutic strategies. The NIH-sponsored "Researching COVID to Enhance Recovery" (RECOVER) initiative includes several retrospective/prospective observational cohort studies enrolling adult, pregnant adult and pediatric patients respectively. RECOVER formed an "OMICS" multidisciplinary task force, including clinicians, pathologists, laboratory scientists and data scientists, charged with developing recommendations to apply cutting-edge system biology technologies to achieve the goals of RECOVER. The task force met biweekly over 14 months, to evaluate published evidence, examine the possible contribution of each "omics" technique to the study of PASC and develop study design recommendations. The OMICS task force recommended an integrated, longitudinal, simultaneous systems biology study of participant biospecimens on the entire RECOVER cohorts through centralized laboratories, as opposed to multiple smaller studies using one or few analytical techniques. The resulting multi-dimensional molecular dataset should be correlated with the deep clinical phenotyping performed through RECOVER, as well as with information on demographics, comorbidities, social determinants of health, the exposome and lifestyle factors that may contribute to the clinical presentations of PASC. This approach will minimize lab-to-lab technical variability, maximize sample size for class discovery, and enable the incorporation of as many relevant variables as possible into statistical models. Many of our recommendations have already been considered by the NIH through the peer-review process, resulting in the creation of a systems biology panel that is currently designing the studies we proposed. This system biology strategy, coupled with modern data science approaches, will dramatically improve our prospects for accurate disease subtype identification, biomarker discovery and therapeutic target identification for precision treatment. The resulting dataset should be made available to the scientific community for secondary analyses. Analogous system biology approaches should be built into the study designs of large observational studies whenever possible.},
}

@article {pmid40805931,
year = {2025},
author = {Mazzonetto, LF and Cordeiro, JFC and Correia, IM and Oliveira, AS and Moraes, C and Brilhadori, J and Gomide, EBG and Kudlacek, M and Machado, DRL and Anjos, JRCD and Santos, APD},
title = {Physical Training Protocols for Improving Dyspnea and Fatigue in Long COVID: A Systematic Review with Meta-Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {15},
pages = {},
pmid = {40805931},
issn = {2227-9032},
abstract = {Objective: This study aimed to evaluate physical training protocols for alleviating long COVID symptoms, especially dyspnea and fatigue, through a systematic review with meta-analysis. Method: Data were collected from EMBASE, LILACS, PubMed, Scopus, CINAHL, Web of Science, and grey literature (Google Scholar, medRxiv). Studies evaluating dyspnea and/or fatigue before and after physical rehabilitation, using validated questionnaires, were included. Studies lacking pre- and post-assessments or physical training were excluded. Two reviewers independently extracted data on intervention type, duration, frequency, intensity, and assessment methods for dyspnea and fatigue. Bias risk was evaluated using the Cochrane tool. Results: Combined methods, such as respiratory muscle training with strength and aerobic exercise, were common for long COVID symptoms. Aerobic exercise notably improved dyspnea and/or fatigue. Among 25 studies, four had a low risk of bias. Meta-analysis of two studies found no significant reduction in fatigue. Conclusion: Combined training methods, particularly aerobic exercise, alleviate dyspnea and fatigue in long COVID. More high-quality studies are needed to confirm these findings.},
}

@article {pmid40804645,
year = {2025},
author = {Paval, NE and Căliman-Sturdza, OA and Lobiuc, A and Dimian, M and Sirbu, IO and Covasa, M},
title = {MicroRNAs in long COVID: roles, diagnostic biomarker potential and detection.},
journal = {Human genomics},
volume = {19},
number = {1},
pages = {90},
pmid = {40804645},
issn = {1479-7364},
support = {285/30.11.2022//Ministerul Cercetării, Inovării şi Digitalizării/ ; },
abstract = {Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), marked by persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection, affects multiple organ systems including the respiratory, cardiovascular, neurological, gastrointestinal, and renal systems. These prolonged effects stem from chronic inflammation, immune dysregulation, and direct viral injury. MicroRNAs (miRNAs)-small non-coding RNAs involved in gene regulation-play a pivotal role in this process by modulating immune responses, inflammation, and cellular stress. Altered miRNA expression patterns during and after infection contribute to the pathogenesis of Long COVID. While conventional miRNA detection techniques have been valuable, they face limitations in sensitivity, throughput, and detecting RNA modifications. This review highlights Oxford Nanopore Sequencing (ONS) as a promising alternative, offering real-time, long-read, amplification-free RNA sequencing that preserves native modifications. ONS enables direct sequencing of full-length miRNAs and their precursors, providing novel insights into miRNA processing and regulatory roles. Despite current challenges with short-read accuracy, ongoing technical advances are improving ONS performance. Its integration in miRNA profiling holds significant potential for uncovering novel regulatory interactions and advancing clinical biomarker discovery in Long COVID and other conditions.},
}

@article {pmid40799952,
year = {2025},
author = {Di Micco, P and Siniscalchi, C and Imbalzano, E and Russo, V and Camporese, G and Lodigiani, C and Meschi, T and Perrella, A},
title = {COVID-19: A Disease Driven by Protease/Antiprotease Imbalance? A Specific Review Five Years into the Pandemic.},
journal = {Infection and drug resistance},
volume = {18},
number = {},
pages = {3967-3975},
pmid = {40799952},
issn = {1178-6973},
abstract = {COVID-19, caused by SARS-CoV-2, has profoundly impacted global health since late 2019. Beyond respiratory complications, the disease involves systemic manifestations driven by immune dysregulation, inflammation, and coagulopathy. Among the many mechanisms implicated in severe disease, a growing body of evidence suggests a central role for the imbalance between proteases and antiproteases. This review examines how dysregulated protease activity contributes to viral entry, cytokine activation, vascular injury, and thrombosis. We focus on the integration of proteolytic systems such as the renin-angiotensin system, coagulation cascade, and neutrophil extracellular traps with established pathways like endothelial dysfunction and immune hyperactivation. Furthermore, we highlight therapeutic strategies aimed at restoring proteolytic balance and discuss the potential relevance of this paradigm in the management of long COVID.},
}

@article {pmid40772993,
year = {2025},
author = {Siqueira, IFB and Figueiredo, LA and Fernandes, CEM and Cintra, LP and de Oliveira, GF and Rios, MA and Maciel, R and Ferretjans, R and Guimarães, NS and Magno, LAV},
title = {Metabolic brain changes in post-acute COVID-19: systematic review and meta-analysis of [18F]-FDG-PET findings.},
journal = {Brain structure & function},
volume = {230},
number = {7},
pages = {128},
pmid = {40772993},
issn = {1863-2661},
mesh = {Humans ; *COVID-19/metabolism/diagnostic imaging/complications ; Positron-Emission Tomography/methods ; Fluorodeoxyglucose F18 ; *Brain/metabolism/diagnostic imaging ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Radiopharmaceuticals ; Glucose/metabolism ; },
abstract = {Individuals with long COVID exhibit neurological and psychiatric symptoms that often persist well beyond the initial SARS-CoV-2 infection. Studies using [18F]-FDG positron emission tomography (FDG-PET) have revealed diverse abnormalities in brain glucose metabolism during the post-acute phase of COVID-19. We conducted a systematic review and meta-analysis to assess the spatial distribution and heterogeneity of brain metabolic changes in patients in the post-acute phase of COVID-19 relative to controls. We searched the MEDLINE, EMBASE, and CENTRAL databases in June 2025 for studies reporting FDG-PET data in patients with post-acute COVID-19 who have persistent neurological symptoms. Of the 14 eligible studies (584 scans), 13 reported glucose hypometabolism across frontoparietal regions, with the frontal cortex being the most consistently affected. This finding was confirmed by meta-analysis, which revealed a large and significant effect in the frontal cortex (Hedges' g = 1.34; 95% CI: 0.79-1.88; p < 0.001), despite high heterogeneity (I[2] = 93.6%). The systematic review indicates that brain metabolism generally improves over time, with widely varying recovery timelines, and consistently correlates hypometabolism with neurological symptom burden. These findings underscore the clinical relevance of frontoparietal hypometabolism in post-acute COVID-19 and its association with neurocognitive deficits, highlighting the need for longitudinal, quantitative PET studies to elucidate temporal dynamics and inform therapeutic development.},
}

Humans
*COVID-19/metabolism/diagnostic imaging/complications
Positron-Emission Tomography/methods
Fluorodeoxyglucose F18
*Brain/metabolism/diagnostic imaging
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Radiopharmaceuticals
Glucose/metabolism

@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 = {1-8},
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 program (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 {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: Scoping Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e72398},
pmid = {40549427},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; Surveys and Questionnaires ; COVID-19/epidemiology ; *Mental Disorders/diagnosis ; SARS-CoV-2 ; },
abstract = {UNLABELLED: 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.

BACKGROUND: 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. Artificial Intelligence (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.

OBJECTIVE: This review aimed to explore the current applications, potential benefits, and issues of AI in medical questionnaires, focusing on its role in 3 main functions: assessment, development, and prediction. The global mental health burden remains severe.

METHODS: The review included peer-reviewed studies that applied AI technologies to medical, psychological, or physiological questionnaires and reported measurable outcomes; non–peer-reviewed, non-English/Chinese, ethically noncompliant, or AI-unrelated studies were excluded. Five databases (PubMed, Embase, Cochrane Library, Web of Science, and CNKI) were searched from inception through September 2024. Three independent reviewers conducted data extraction, quality appraisal using the Joanna Briggs Institute tools, and narrative synthesis of AI applications across questionnaire assessment, development, and prediction tasks.

RESULTS: Of 49,091 publications, a total of 14 (0.03%) studies met the inclusion criteria. AI technologies showed 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.

CONCLUSIONS: 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 {pmid40300093,
year = {2025},
author = {Rane Levendovszky, S and Patel, P and Zhu, C and Rutman, AM and Basha, MM},
title = {Neuroimaging biomarkers of post-acute sequelae of Coronavirus Disease 2019.},
journal = {The British journal of radiology},
volume = {98},
number = {1172},
pages = {1165-1175},
doi = {10.1093/bjr/tqaf090},
pmid = {40300093},
issn = {1748-880X},
support = {R01 HL162743/HL/NHLBI NIH HHS/United States ; //Chronic Post COVID-19 Infection Neuroimaging and Cerebrovascular Imaging/ ; //Bayer Healthcare LLC/ ; //Long terms effects of COVID-19/ ; },
mesh = {Humans ; *COVID-19/complications/diagnostic imaging ; *Neuroimaging/methods ; *Brain/diagnostic imaging/pathology ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; Biomarkers ; Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging ; },
abstract = {COVID-19, caused by SARS-CoV-2, has led to the condition known as Long COVID or post-acute sequelae of COVID-19 (PASC), where individuals experience persistent debilitating symptoms long after the initial infection. We provide here a comprehensive review of findings in the central nervous system associated with PASC. Neuroimaging has been instrumental in identifying brain changes associated with PASC. Structural MRI studies consistently reveal grey matter volume reductions in the frontal and temporal lobes and white matter hyperintensities, particularly in the periventricular regions. Studies especially found these changes to correlate strongly with cognitive deficits. Diffusion tensor imaging has shown increased tissue damage and oedema in the brain's white matter tracts, particularly in the sagittal stratum and thalamic radiation. Resting-state functional MRI studies indicate altered brain connectivity in PASC patients, especially in those with post-traumatic stress symptoms. Reduced connectivity within and between critical networks, such as the default mode network and the executive control network, has been observed. These changes correlate with cognitive impairments, such as attention and memory deficits. Dynamic functional connectivity analyses further reveal that PASC patients spend less time in states with rich inter-regional connectivity, and transitions between connectivity states were linked to post-traumatic stress disorder symptoms. Positron emission tomography scans have shown hypometabolism in the frontal and temporal lobes, particularly in regions associated with memory and executive functions. Hypometabolism in the hippocampus and thalamus is linked to symptoms like anosmia and fatigue. Despite the heterogeneity in clinical presentations and diagnostic criteria, these neuroimaging findings underscore the significant impact of COVID-19 on brain structure and function. Continued research using advanced imaging techniques is essential for a deeper understanding of PASC's neurological effects. This will aid in developing targeted interventions and improving outcomes for those affected by Long COVID and inform studies investigating downstream effects of viral infections on the brain.},
}

Humans
*COVID-19/complications/diagnostic imaging
*Neuroimaging/methods
*Brain/diagnostic imaging/pathology
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Biomarkers
Magnetic Resonance Imaging/methods
Diffusion Tensor Imaging

@article {pmid39083202,
year = {2024},
author = {Huang, Y and Wang, W and Liu, Y and Wang, Z and Cao, B},
title = {COVID-19 vaccine updates for people under different conditions.},
journal = {Science China. Life sciences},
volume = {67},
number = {11},
pages = {2323-2343},
pmid = {39083202},
issn = {1869-1889},
mesh = {Humans ; *COVID-19 Vaccines/immunology/administration & dosage ; *COVID-19/prevention & control/immunology/epidemiology ; *SARS-CoV-2/immunology ; Vaccine Efficacy ; Immunocompromised Host/immunology ; },
abstract = {SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today. The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections. Therefore, it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available. In this review, we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants, which can significantly improve immune protection. While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly, individuals with chronic comorbidities (e.g., diabetes with poor blood glucose control, those on maintenance dialysis), or those who are immunocompromised compared to the general population, administering multiple doses can result in a strong protective immune response that outweighs potential risks. However, caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications. In conclusion, individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection, as well as to avoid the potential development of long COVID.},
}

Humans
*COVID-19 Vaccines/immunology/administration & dosage
*COVID-19/prevention & control/immunology/epidemiology
*SARS-CoV-2/immunology
Vaccine Efficacy
Immunocompromised Host/immunology

@article {pmid38973985,
year = {2024},
author = {Dalmau, R and Alanazi, AM and Arora, M and Banerjee, A and Bianco, E and Gaalema, DE and Goma, FM and Hasegawa, K and Komiyama, M and Pérez Ríos, M and Willett, J and Wang, Y},
title = {A Complex Interplay: Navigating the Crossroads of Tobacco Use, Cardiovascular Disease, and the COVID-19 Pandemic: A WHF Policy Brief.},
journal = {Global heart},
volume = {19},
number = {1},
pages = {55},
pmid = {38973985},
issn = {2211-8179},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; *Cardiovascular Diseases/epidemiology/prevention & control ; *Tobacco Use/epidemiology ; *SARS-CoV-2 ; Pandemics ; Risk Factors ; Health Policy ; },
abstract = {The Coronavirus Disease 2019, commonly referred to as COVID-19, is responsible for one of the deadliest pandemics in human history. The direct, indirect and lasting repercussions of the COVID-19 pandemic on individuals and public health, as well as health systems can still be observed, even today. In the midst of the initial chaos, the role of tobacco as a prognostic factor for unfavourable COVID-19 outcomes was largely neglected. As of 2023, numerous studies have confirmed that use of tobacco, a leading risk factor for cardiovascular and other diseases, is strongly associated with increased risks of severe COVID-19 complications (e.g., hospitalisation, ICU admission, need for mechanical ventilation, long COVID, etc.) and deaths from COVID-19. In addition, evidence suggests that COVID-19 directly affects multiple organs beyond the respiratory system, disproportionately impacting individuals with comorbidities. Notably, people living with cardiovascular disease are more prone to experiencing worse outcomes, as COVID-19 often inherently manifests as thrombotic cardiovascular complications. As such, the triad of tobacco, COVID-19 and cardiovascular disease constitutes a dangerous cocktail. The lockdowns and social distancing measures imposed by governments have also had adverse effects on our lifestyles (e.g., shifts in diets, physical activity, tobacco consumption patterns, etc.) and mental well-being, all of which affect cardiovascular health. In particular, vulnerable populations are especially susceptible to tobacco use, cardiovascular disease and the psychological fallout from the pandemic. Therefore, national pandemic responses need to consider health equity as well as the social determinants of health. The pandemic has also had catastrophic impacts on many health systems, bringing some to the brink of collapse. As a result, many health services, such as services for cardiovascular disease or tobacco cessation, were severely disrupted due to fears of transmission and redirection of resources for COVID-19 care. Unfortunately, the return to pre-pandemic levels of cardiovascular disease care activity has stagnated. Nevertheless, digital solutions, such as telemedicine and apps, have flourished, and may help reduce the gaps. Advancing tobacco control was especially challenging due to interference from the tobacco industry. The industry exploited lingering uncertainties to propagate misleading information on tobacco and COVID-19 in order to promote its products. Regrettably, the links between tobacco use and risk of SARS-CoV-2 infection remain inconclusive. However, a robust body of evidence has, since then, demonstrated that tobacco use is associated with more severe COVID-19 illness and complications. Additionally, the tobacco industry also repeatedly attempted to forge partnerships with governments under the guise of corporate social responsibility. The implementation of the WHO Framework Convention on Tobacco Control could address many of the aforementioned challenges and alleviate the burden of tobacco, COVID-19, and cardiovascular disease. In particular, the implementation of Article 5.3 could protect public health policies from the vested interests of the industry. The world can learn from the COVID-19 pandemic to better prepare for future health emergencies of international concern. In light of the impact of tobacco on the COVID-19 pandemic, it is imperative that tobacco control remains a central component in pandemic preparedness and response plans.},
}

Humans
*COVID-19/epidemiology/prevention & control
*Cardiovascular Diseases/epidemiology/prevention & control
*Tobacco Use/epidemiology
*SARS-CoV-2
Pandemics
Risk Factors
Health Policy

@article {pmid37832998,
year = {2023},
author = {Voss, JG and Pinto, MD and Burton, CW},
title = {How do the Social Determinants of Health Impact the Post-Acute Sequelae of COVID-19: A Critical Review.},
journal = {The Nursing clinics of North America},
volume = {58},
number = {4},
pages = {541-568},
doi = {10.1016/j.cnur.2023.07.004},
pmid = {37832998},
issn = {1558-1357},
mesh = {Humans ; *COVID-19 ; Post-Acute COVID-19 Syndrome ; Retrospective Studies ; Social Determinants of Health ; Disease Progression ; },
abstract = {The review critically analyzes the social determinants of health (SDOH) variables in the current literature of patients with post-acute sequelae (PASC) of COVID-19 in the United States. Race, gender, and age were discussed as well as health outcomes, severity of illness, and phenotypes of long-COVID. Most research was retrospectively with samples that had access to health insurance, which did not capture populations with poor or no access to health care. More research is needed that directly addresses the impact on SDOH on PASC. The current literature is sparse and provides little actionable information.},
}

Humans
*COVID-19
Post-Acute COVID-19 Syndrome
Retrospective Studies
Social Determinants of Health
Disease Progression

@article {pmid37797257,
year = {2023},
author = {Baker, MG and Kvalsvig, A and Plank, MJ and Geoghegan, JL and Wall, T and Tukuitonga, C and Summers, J and Bennett, J and Kerr, J and Turner, N and Roberts, S and Ward, K and Betty, B and Huang, QS and French, N and Wilson, N},
title = {Continued mitigation needed to minimise the high health burden from COVID-19 in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {136},
number = {1583},
pages = {67-91},
doi = {10.26635/6965.6247},
pmid = {37797257},
issn = {1175-8716},
mesh = {Humans ; *COVID-19/epidemiology/prevention & control ; New Zealand/epidemiology ; Post-Acute COVID-19 Syndrome ; Pandemics/prevention & control ; Maori People ; },
abstract = {In this article we review the COVID-19 pandemic experience in Aotearoa New Zealand and consider the optimal ongoing response strategy. We note that this pandemic virus looks likely to result in future waves of infection that diminish in size over time, depending on such factors as viral evolution and population immunity. However, the burden of disease remains high with thousands of infections, hundreds of hospitalisations and tens of deaths each week, and an unknown burden of long-term illness (long COVID). Alongside this there is a considerable burden from other important respiratory illnesses, including influenza and RSV, that needs more attention. Given this impact and the associated health inequities, particularly for Māori and Pacific Peoples, we consider that an ongoing respiratory disease mitigation strategy is appropriate for New Zealand. As such, the previously described "vaccines plus" approach (involving vaccination and public health and social measures), should now be integrated with the surveillance and control of other important respiratory infections. Now is also a time for New Zealand to build on the lessons from the COVID-19 pandemic to enhance preparedness nationally and internationally. New Zealand's experience suggests elimination (or ideally exclusion) should be the default first choice for future pandemics of sufficient severity.},
}

Humans
*COVID-19/epidemiology/prevention & control
New Zealand/epidemiology
Post-Acute COVID-19 Syndrome
Pandemics/prevention & control
Maori People

@article {pmid36731604,
year = {2023},
author = {Crosier, R and Kafil, TS and Paterson, DI},
title = {Imaging for Cardiovascular Complications of COVID-19: Cardiac Manifestations in Context.},
journal = {The Canadian journal of cardiology},
volume = {39},
number = {6},
pages = {779-792},
pmid = {36731604},
issn = {1916-7075},
support = {//CIHR/Canada ; },
mesh = {Humans ; *COVID-19/complications ; *COVID-19 Vaccines/adverse effects ; Heart ; *Myocarditis/diagnostic imaging/etiology ; Post-Acute COVID-19 Syndrome ; RNA, Messenger ; },
abstract = {After the first confirmed case in 2019, COVID-19 rapidly spread worldwide and overwhelmed the medical community. In the intervening time, we have learned about COVID-19's clinical manifestations and have developed effective therapies and preventative vaccines. Severe COVID-19 infection is associated with many cardiovascular disorders in the acute phase, and patients recovered from illness can also manifest long-term sequelae, including long COVID syndrome. Furthermore, severe acute respiratory syndrome-related coronavirus-2 messenger RNA (mRNA) vaccination can trigger rare cases of myopericarditis. We have gained significant knowledge of the acute and long-term cardiovascular complications of COVID-19- and mRNA vaccine-associated myocarditis through clinical and investigative studies using cardiac imaging. In this review, we describe how cardiovascular imaging can be used to understand the cardiovascular complications and cardiac injury associated with acute COVID-19 infection, review the imaging findings in patients recovered from illness, and discuss the role and limitations of cardiac imaging in COVID-19 mRNA vaccine-associated myocarditis.},
}

Humans
*COVID-19/complications
*COVID-19 Vaccines/adverse effects
Heart
*Myocarditis/diagnostic imaging/etiology
Post-Acute COVID-19 Syndrome
RNA, Messenger

@article {pmid35462637,
year = {2022},
author = {Saha, SA and Russo, AM and Chung, MK and Deering, TF and Lakkireddy, D and Gopinathannair, R},
title = {COVID-19 and Cardiac Arrhythmias: a Contemporary Review.},
journal = {Current treatment options in cardiovascular medicine},
volume = {24},
number = {6},
pages = {87-107},
pmid = {35462637},
issn = {1092-8464},
support = {IK6 BX006185/BX/BLRD VA/United States ; R01 HL111314/HL/NHLBI NIH HHS/United States ; R01 HL158071/HL/NHLBI NIH HHS/United States ; },
abstract = {PURPOSE OF REVIEW: A significant proportion of patients infected by the severe acute respiratory syndrome-coronavirus (SARS-CoV2) (COVID-19) also have disorders affecting the cardiac rhythm. In this review, we provide an in-depth review of the pathophysiological mechanisms underlying the associated arrhythmic complications of COVID-19 infection and provide pragmatic, evidence-based recommendations for the clinical management of these conditions.

RECENT FINDINGS: Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death.

SUMMARY: Arrhythmic complications from acute COVID-19 infection are commonly encountered in clinical practice, and COVID-19 patients with cardiac complications tend to have worse clinical outcomes than those without. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. Some manifestations, such as the long COVID syndrome, may lead to residual symptoms several months after acute infection. As the pandemic evolves with the discovery of new SARS-CoV2 variants, development and use of newer anti-viral and immuno-modulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.},
}

@article {pmid34870392,
year = {2021},
author = {Zimmermann, P and Pittet, LF and Curtis, N},
title = {How Common is Long COVID in Children and Adolescents?.},
journal = {The Pediatric infectious disease journal},
volume = {40},
number = {12},
pages = {e482-e487},
pmid = {34870392},
issn = {1532-0987},
mesh = {Adolescent ; COVID-19/*complications/epidemiology/ethnology/*pathology ; Child ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {In children, the risk of coronavirus disease (COVID) being severe is low. However, the risk of persistent symptoms following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is uncertain in this age group, and the features of "long COVID" are poorly characterized. We reviewed the 14 studies to date that have reported persistent symptoms following COVID in children and adolescents. Almost all the studies have major limitations, including the lack of a clear case definition, variable follow-up times, inclusion of children without confirmation of SARS-CoV-2 infection, reliance on self- or parent-reported symptoms without clinical assessment, nonresponse and other biases, and the absence of a control group. Of the 5 studies which included children and adolescents without SARS-CoV-2 infection as controls, 2 did not find persistent symptoms to be more prevalent in children and adolescents with evidence of SARS-CoV-2 infection. This highlights that long-term SARS-CoV-2 infection-associated symptoms are difficult to distinguish from pandemic-associated symptoms.},
}

Adolescent
COVID-19/*complications/epidemiology/ethnology/*pathology
Child
Humans
*SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34631916,
year = {2021},
author = {Sandler, CX and Wyller, VBB and Moss-Morris, R and Buchwald, D and Crawley, E and Hautvast, J and Katz, BZ and Knoop, H and Little, P and Taylor, R and Wensaas, KA and Lloyd, AR},
title = {Long COVID and Post-infective Fatigue Syndrome: A Review.},
journal = {Open forum infectious diseases},
volume = {8},
number = {10},
pages = {ofab440},
pmid = {34631916},
issn = {2328-8957},
abstract = {Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed "long-COVID"), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after COVID-19. In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16-20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%-35% at 6 months. To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions.},
}

@article {pmid33857435,
year = {2021},
author = {Song, WJ and Hui, CKM and Hull, JH and Birring, SS and McGarvey, L and Mazzone, SB and Chung, KF},
title = {Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses.},
journal = {The Lancet. Respiratory medicine},
volume = {9},
number = {5},
pages = {533-544},
pmid = {33857435},
issn = {2213-2619},
mesh = {COVID-19/*complications/*physiopathology ; Cough/*etiology/physiopathology ; Humans ; Inflammation/*etiology/physiopathology ; Nervous System Diseases/*etiology/physiopathology ; *Neuroimmunomodulation ; SARS-CoV-2 ; Syndrome ; },
abstract = {Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.},
}

COVID-19/*complications/*physiopathology
Cough/*etiology/physiopathology
Humans
Inflammation/*etiology/physiopathology
Nervous System Diseases/*etiology/physiopathology
*Neuroimmunomodulation
SARS-CoV-2
Syndrome

@article {pmid40819231,
year = {2025},
author = {Levin, J and Bradshaw, M},
title = {The Challenge of Long COVID: Is the Pandemic Really Over?.},
journal = {Public health reports (Washington, D.C. : 1974)},
volume = {},
number = {},
pages = {333549251358665},
doi = {10.1177/00333549251358665},
pmid = {40819231},
issn = {1468-2877},
abstract = {Sequelae of SARS-CoV-2 infection began appearing among patients who had COVID-19 within months of the first wave of the COVID-19 pandemic in 2020. This phenomenon, termed post-COVID-19 condition and also known as long COVID, has been a source of controversy among physicians, as presentation of long COVID has been a somewhat mysterious constellation of signs and symptoms that seem mostly impervious to efficacious treatment. Although a considerable amount has been learned about the pathophysiology and other biomedical features of long COVID, the epidemiologic parameters of long COVID, including incidence and prevalence, are uncertain in the United States and globally. The best estimates are that millions of people have long COVID. Despite the declining incidence of COVID-19, the low case fatality of long COVID suggests that its prevalence is poised to continue to grow. This increasing prevalence of long COVID presents a challenge for the public health sector. Here, we examine the public health implications of long COVID. We offer policy recommendations, including ending congratulatory talk that the pandemic is over, encouraging more focused attention from the United States and global nongovernmental organizations, and establishing a multinational research initiative to better understand and respond to long COVID and other postviral and postinfectious chronic conditions. Although COVID-19 may not be as widespread and disruptive as in the early months of the pandemic, it would be a mistake to presume that, because the acute crisis is behind us, the pandemic is past. Long COVID is an ongoing public health threat and merits our concern.},
}

@article {pmid40769733,
year = {2025},
author = {Wilson, CM and Boright, LE and Henshaw, AM and Naccarato, A},
title = {Role of rehabilitation in palliative care after the COVID-19 pandemic: a narrative review.},
journal = {Annals of palliative medicine},
volume = {14},
number = {4},
pages = {379-392},
doi = {10.21037/apm-25-6},
pmid = {40769733},
issn = {2224-5839},
mesh = {Humans ; *COVID-19/rehabilitation/epidemiology ; *Palliative Care/organization & administration ; Pandemics ; SARS-CoV-2 ; },
abstract = {BACKGROUND AND OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic resulted in an historic disruption and transformation of the healthcare system, including the management of individuals with serious illness. Rehabilitation for patients facing serious or life-threatening illness is underutilized and poorly understood, resulting in unwarranted suffering, disability, and poorly coordinated care. This narrative review aims to describe the impact of the COVID-19 pandemic on the role and scope of rehabilitation within the context of serious illness and palliative care.

METHODS: A focused review of the literature included selected articles identified from three databases published from January 2020 to January 2025. Findings were synthesized narratively, with a focus on identifying themes and gaps in the literature related to two main topics: (I) the evidence related to rehabilitation for those with serious or life-threatening COVID-19 during the pandemic and (II) how rehabilitation for patients with serious illness has been transformed after emerging from the pandemic (including non-COVID diagnoses such as cancer, neurologic conditions, etc.).

KEY CONTENT AND FINDINGS: The key themes identified during the COVID-19 pandemic emphasized the need for early rehabilitation, interdisciplinary care, and an emphasis on cardiopulmonary principles for rehabilitation. Themes identified during the pandemic also included the emerging role of telerehabilitation, and need for evidence and clinical guidelines for serious illnesses (including long COVID). Themes related to the transformative effect on palliative rehabilitation after the pandemic included an increased importance and focus on coordination of care and interdisciplinary care for those with serious illness and increased focus on mental health and social determinants of health (SDOH). Additionally, there appears to be increased infrastructure and activity related to research, advocacy, and awareness for palliative rehabilitation.

CONCLUSIONS: The COVID-19 global pandemic highlighted the need for high quality, coordinated palliative care, including rehabilitation services, for patients facing a serious or life-threatening illness. Due to the benefits to a person's quality of life (QoL), dignity, and comfort, there is increasing evidence of the importance of seamless, ongoing access to rehabilitation services for patients with serious illness.},
}

Humans
*COVID-19/rehabilitation/epidemiology
*Palliative Care/organization & administration
Pandemics
SARS-CoV-2

@article {pmid40762988,
year = {2025},
author = {Gusmão, ACS and Scaléa, ACR and Uehara, SCDSA},
title = {Symptoms of long COVID in children and adolescents: a scoping review.},
journal = {Revista da Escola de Enfermagem da U S P},
volume = {59},
number = {},
pages = {e20240435},
pmid = {40762988},
issn = {1980-220X},
mesh = {Humans ; Adolescent ; Child ; *COVID-19/complications/diagnosis/epidemiology/physiopathology ; Age Factors ; },
abstract = {OBJECTIVE: To map the symptoms of Long Covid (LC) presented by children and adolescents.

METHOD: This is a scoping review, using the search engines Web of Science, Scopus, Virtual Health Library, and PUBMED, following the principles of the Joanna Briggs Institute.

RESULTS: Sixteen studies were selected, which showed that fatigue, headache, dyspnea, and cough were the most frequent symptoms of LC. There is a tendency for the development of child-adolescent LC related to the increase in age range, and the correlation between LC and predominant sex proved to be inconclusive. The presence of comorbidities, such as obesity, respiratory, neurological and renal diseases, was the most reported and a study showed an association between Covid-19 vaccine protection and LC.

CONCLUSION: This review points to a plurality of symptomatic manifestations of LC in children and adolescents, changing according to age group and health history.},
}

Humans
Adolescent
Child
*COVID-19/complications/diagnosis/epidemiology/physiopathology
Age Factors

@article {pmid40754067,
year = {2025},
author = {Peine, C and Stoliaroff-Pepin, A and Reinacher, U and Heldt, K and Sarganas, G and Piechotta, V and Mikolajewska, A and Pilic, A and Barkowski, N and Bleve, D and Giebeler, MH and Poser, S and Searle, L and Kißner, E and Nitsche, L and Bayram, F and Siemens, W and Ziegler, A and Meerpohl, JJ and Sandmann, F and Wichmann, O and Harder, T},
title = {Effectiveness of COVID-19 vaccines against post COVID-19 condition/long COVID: systematic review and meta-analysis.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmi.2025.07.026},
pmid = {40754067},
issn = {1469-0691},
abstract = {BACKGROUND: Persons infected with SARS-CoV-2 can develop long-term symptoms known as post-COVID-19-condition (PCC; symptoms ≥three months after infection) or long-COVID (LC; symptoms ≥one month after infection). Vaccination against COVID-19 might prevent PCC/LC, but the extent of protection is unclear.

OBJECTIVE: Aim of this systematic review was to evaluate vaccine efficacy/effectiveness (VE) of COVID-19 vaccines given prior to SARS-CoV-2-infection in preventing PCC or LC.

METHODS DATA SOURCES: Studies were identified in Embase, MEDLINE, PreView, COVID-19 L.OVE repository and Cochrane Library up to August 1, 2024.

Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) that investigated immunization with a COVID-19 vaccine before SARS-CoV-2-infection were eligible, irrespective of participant age and sex.

ASSESSMENT OF RISK OF BIAS: Risk of bias was assessed using ROBINS-I.

METHODS OF DATA SYNTHESIS: Primary outcome was PCC, secondary outcomes were LC, time until reconvalescence, limitations in every day activity, and quality of life. Meta-analyses were primarily conducted using the random-effects model.

RESULTS: 6423 records were screened and 65 non-randomized studies of interventions (NRSI) reporting adjusted estimates were included, comprising >5.7 mio.

PARTICIPANTS: VE for ≥one vaccine dose against PCC was 41.0% (95% confidence interval (CI) 27.8%; 51.7%; 22 NRSI, certainty of evidence: low). VE after one, two or three doses versus unvaccinated was 19.1% (-119.4%; 70.2%, three NRSI), 43.2% (4.5%; 66.2%; four NRSI) and 70.0% (30.0%; 87.0%; one NRSI), respectively. In <18-years-olds, VE against PCC was 26% for ≥one dose (-4%; 48%, one NRSI) and in >60-years-olds 41% (17%; 59%, one NRSI). VE after pre-Omicron-SARS-CoV-2 infection was 32.1% (-54.3%; 70.1%, three NRSI) and 20.9% (-10.1%; 43.3%, two NRSI) after Omicron-infection. Sensitivity analyses indicated no influence of risk of bias and effect measure.

CONCLUSIONS: COVID-19 vaccines may be moderately effective in preventing PCC/LC. VE may increase with number of vaccine doses administered.},
}