@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.},
}

@article {pmid40744021,
year = {2025},
author = {Komaroff, AL and Dantzer, R},
title = {Causes of symptoms and symptom persistence in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102259},
doi = {10.1016/j.xcrm.2025.102259},
pmid = {40744021},
issn = {2666-3791},
abstract = {Debilitating symptoms for many years can follow acute COVID-19 ("long COVID"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural circuits constitute a symptom-generating pathway, activated by neuroinflammation, which may be targeted by therapeutics to quell neuroinflammation. Many factors cause the symptoms to become chronic, including persistent infectious agents (and/or their nucleic acids and antigens) and the fact that many of the underlying biological abnormalities reinforce each other, creating ongoing physiological vicious cycles.},
}

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

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

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

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

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

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

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

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

@article {pmid40717478,
year = {2025},
author = {Bajić, D and Todorović, N and Popović, ML and Plazačić, M and Mihajlović, A},
title = {Immunity's core reset: Synbiotics and gut microbiota in the COVID-19 era.},
journal = {Innate immunity},
volume = {31},
number = {},
pages = {17534259251362023},
pmid = {40717478},
issn = {1753-4267},
mesh = {Humans ; *COVID-19/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Synbiotics/administration & dosage ; *SARS-CoV-2/immunology ; *Dysbiosis/immunology/microbiology ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Inflammation/immunology ; },
abstract = {The gut microbiome plays a crucial role in shaping immune responses, and its connection to immunity has never been more relevant than in the COVID-19 era. The interaction between gut microbes and the immune system, known as microbiome-immunity crosstalk, influences both how the body responds to infections and how well it recovers. COVID-19, whether in its acute phase or lingering as long COVID, has been linked to disturbances in the gut microbiome. During infection, many patients experience dysbiosis-an imbalance in gut bacteria-that can contribute to immune dysfunction and excessive inflammation. This imbalance may not only worsen the severity of the disease but also prolong recovery, leading to persistent symptoms like fatigue, brain fog, and digestive issues. Long COVID, in particular, has been associated with ongoing immune dysregulation, where the body's defense system remains in a state of heightened activation, causing chronic inflammation. Given the strong link between gut health and immunity, there is growing interest in strategies to restore microbial balance. Synbiotics-combinations of probiotics (beneficial bacteria) and prebiotics (nutrients that support them)-are being explored as a potential therapeutic approach. By replenishing beneficial gut microbes, synbiotics may help regulate immune responses, reduce inflammation, and support overall recovery from COVID-19. Emerging research suggests that improving gut health could enhance the body's ability to fight infections and recover more efficiently. As we continue to understand the long-term impact of COVID-19, focusing on the gut microbiome offers a promising path forward. Supporting a balanced and diverse microbiome through diet, lifestyle, and targeted interventions like synbiotics may provide a natural way to strengthen immunity and improve health outcomes in both acute and long COVID cases.},
}

Humans
*COVID-19/immunology/microbiology
*Gastrointestinal Microbiome/immunology
*Synbiotics/administration & dosage
*SARS-CoV-2/immunology
*Dysbiosis/immunology/microbiology
Probiotics/therapeutic use
Prebiotics/administration & dosage
Inflammation/immunology

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid40684905,
year = {2025},
author = {Gershon, AS and Fung, D and Lam, GY},
title = {Diagnosing Respiratory Long COVID: A Practical Approach.},
journal = {Chest},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chest.2025.06.028},
pmid = {40684905},
issn = {1931-3543},
abstract = {Long COVID or a post-COVID condition, defined as the persistence of symptoms at least 3 months after acute COVID-19 infection, is a novel condition in which a definitive diagnostic marker and treatment have yet to be found. This condition, which has been estimated to impact > 65 million individuals worldwide, manifests with multisystem involvement, most commonly presenting with fatigue, brain fog, dyspnea, cough, or a combination thereof. The burden of these symptoms can range from mild to severe, with many patients reporting an inability to return to usual activities. Herein, we present several hypothetical but clinically representative case reports to allow discussion around how we approach the diagnosis of respiratory symptoms of long COVID in those with and without chronic lung disease.},
}

@article {pmid40683613,
year = {2025},
author = {Chen, K and Wang, Z and Li, J and Xu, Y and Gu, S and Li, H and Li, J and Zhang, Y and Mao, N},
title = {Chronic inflammation in Long COVID relationship to autoimmune diseases.},
journal = {Autoimmunity reviews},
volume = {24},
number = {10},
pages = {103882},
doi = {10.1016/j.autrev.2025.103882},
pmid = {40683613},
issn = {1873-0183},
abstract = {The new coronavirus pandemic has been ongoing for nearly five years. In addition to the severe symptoms in the acute phase, it is accompanied by long-term complications and sequelae involving the respiratory, neurological, immune, circulatory, and gastrointestinal systems for several months or even years, which is called the Long COVID. Many studies have suggested that systemic chronic inflammation caused by residual viral components may be one of the pathophysiologic mechanisms of Long COVID. In this paper, we will review the autoimmune diseases caused by chronic inflammation. In particular, cytokine storminess, pro-inflammatory responses of inflammatory vesicles, mast cell activation syndrome, changes in the gut microbiota, molecular mimicry, reactivation of latent viruses, and coagulation abnormalities are among the pathways that contribute to autoimmune diseases, including Systemic Lupus Erythematosus, Guillain-Barré syndrome, rheumatoid arthritis. We intervene in the treatment of the disease with probiotics, immunoglobulins, the RECOVER clinical trial model, and immunomodulatory drugs. The aim is to enhance understanding of the pathophysiological mechanism of Long COVID and to provide a reference for the immunotherapy of patients.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid40640033,
year = {2025},
author = {Giunta, S and Giuliani, A and Sabbatinelli, J and Olivieri, F},
title = {A multidimensional immunological perspective on long COVID.},
journal = {Cytokine & growth factor reviews},
volume = {84},
number = {},
pages = {1-11},
doi = {10.1016/j.cytogfr.2025.07.001},
pmid = {40640033},
issn = {1879-0305},
mesh = {Humans ; *COVID-19/immunology/complications ; *SARS-CoV-2/immunology ; Inflammation/immunology ; Cytokines/immunology ; Post-Acute COVID-19 Syndrome ; Autoantibodies/immunology/blood ; },
abstract = {Long COVID is a chronic condition that arises after SARS-CoV-2 infection and is characterized by persistent and often debilitating symptoms, such as fatigue, cognitive dysfunction ("brain fog"), dyspnea, and autonomic disturbances. Increasing evidence suggests that Long COVID shares key immunopathological mechanisms with autoimmune diseases, primarily sustained immune dysregulation. In individuals with genetic or immunological susceptibility, SARS-CoV-2 infection can trigger the production of autoantibodies targeting cytokines, membrane receptors, and components of the autonomic nervous system (ANS), thereby disrupting neuroimmune homeostasis. This immune imbalance may impair anti-inflammatory regulatory pathways, such as the cholinergic anti-inflammatory pathway (CAP), and may contribute to a chronic state of inflammation and autoimmunity. One proposed contributor to this process is inflammaging - a chronic, low-grade inflammation associated with aging - which may not only predispose individuals to Long COVID but may also be amplified by the persistent immune activation seen in this condition. In this perspective, we propose a conceptual framework in which inflammaging, immune-tolerance breakdown, and autonomic dysfunctions interact to sustain the pathophysiology of Long COVID. We discuss emerging biomarkers across these axes, including inflammatory cytokines, circulating autoantibodies, immune cell phenotypes, epigenetic modifications, and heart rate variability. Advances in inflammaging-related biomarkers and biological clocks may support early identification of individuals at higher risk for persistent immune and autonomic dysregulation, ultimately informing more precise diagnostic and therapeutic strategies for Long COVID.},
}

Humans
*COVID-19/immunology/complications
*SARS-CoV-2/immunology
Inflammation/immunology
Cytokines/immunology
Post-Acute COVID-19 Syndrome
Autoantibodies/immunology/blood

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

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

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

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

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

CLINICAL TRIAL NUMBER: Not applicable.},
}

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

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

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

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

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

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

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

@article {pmid40583757,
year = {2025},
author = {Cornwell, WK and Levine, BD and Baptiste, D and Bhave, N and Desai, S and Dineen, E and Durstenfeld, M and Edward, J and Huang, M and Jacobsen, R and Kim, JH and Spatz, E and , },
title = {Exercise Intolerance and Response to Training in Patients With Postacute Sequelae of SARS-CoV2 (Long COVID): A Scientific Statement From the American Heart Association.},
journal = {Circulation},
volume = {152},
number = {5},
pages = {e50-e62},
doi = {10.1161/CIR.0000000000001348},
pmid = {40583757},
issn = {1524-4539},
mesh = {Humans ; *COVID-19/physiopathology/complications/therapy ; *Exercise Tolerance ; American Heart Association ; United States ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; *Exercise Therapy/methods ; Cardiovascular Deconditioning ; Quality of Life ; Exercise ; },
abstract = {The postacute sequelae of SARS-CoV-2, also known as Long COVID, may affect 10% to 25% of individuals diagnosed with SARS-CoV-2. More than 100 symptoms have been reported among patients with Long COVID, but almost all patients report severe fatigue, orthostatic intolerance, shortness of breath, and reductions in exercise tolerance. Emerging data suggest that cardiovascular deconditioning plays a major role in the development of this syndrome and that reductions in functional capacity among patients with Long COVID are comparable to reductions seen among individuals with cardiovascular deconditioning resulting from bed rest. Concern has been raised about the use of exercise training as part of the management strategy for patients with Long COVID. However, exercise training appropriately tailored to the patient with cardiovascular deconditioning may be an effective strategy to facilitate improvement in symptoms. This American Heart Association scientific statement provides a concise yet comprehensive overview of mechanisms contributing to development of Long COVID and methods by which exercise training may be applied to this unique patient population to alleviate symptoms and improve quality of life. In addition, methods of reintroducing exercise and return to play among athletes affected by COVID-19 are discussed.},
}

Humans
*COVID-19/physiopathology/complications/therapy
*Exercise Tolerance
American Heart Association
United States
SARS-CoV-2
Post-Acute COVID-19 Syndrome
*Exercise Therapy/methods
Cardiovascular Deconditioning
Quality of Life
Exercise

@article {pmid40582622,
year = {2025},
author = {Xu, K and He, W and Yu, B and Wang, JJ and Wu, J and Wang, DW},
title = {Unveiling the silent threat: COVID-19 and myocardial injury.},
journal = {Pharmacology & therapeutics},
volume = {273},
number = {},
pages = {108904},
doi = {10.1016/j.pharmthera.2025.108904},
pmid = {40582622},
issn = {1879-016X},
abstract = {Since COVID-19 firstly appeared in 2019 December, it has been defined as an infectious disease mainly performing lung symptoms, which contracted more attention. However, more and more findings indicate myocardial injury appears in considerable proportion of COVID-19 patients (30 % - 50 %) not only but also major cause leading to the death in patients, many of whom may be even without severe respiratory symptoms. Meanwhile myocarditis after injecting vaccines has been paid more attention to globally which always performs uncontrollable inflammation and lead to death. Now myocardial injury has been a main complication in patients with long COVID-19, which is worthy of attention. Furthermore, myocardial injury or myocarditis is detectable and treatable. In order to abstract attention to myocardial injury associated with COVID-19 and provide more evidence and experience for patients who still suffer myocardial injury from COVID-19 vaccines or long COVID-19, the review comprehensively summarized previous researches from pathogenesis, clinical symptoms, diagnosis and treatment and emphasized the crucial role of RASS inhibitors especially ARBs.},
}

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

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

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

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

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