@article {pmid40748784,
year = {2025},
author = {Pollett, S and Agan, BK and Letizia, AG and Richard, SA and Porter, C and Epsi, NJ and Haigney, M and Saunders, D and Colombo, R and Burgess, TH and Morris, M and Tribble, DR and La Croix, C and Jones, M and O'Connell, RJ},
title = {Long COVID and the Military: A Current Research Landscape, Knowledge Gaps, and Future Directions.},
journal = {Military medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/milmed/usaf343},
pmid = {40748784},
issn = {1930-613X},
support = {HU00012120103//Defense Health Program/ ; },
abstract = {INTRODUCTION: This narrative review highlights the impact and epidemiology of post-COVID conditions (PCC, 'Long COVID') in military service members and beneficiaries, characterizing the threat of Long COVID to military readiness. We leveraged this review to propose a Long COVID research road map for Military Health System (MHS)-based studies, identifying key questions and knowledge gaps that the Department of Defense research enterprise is well-positioned to address.

MATERIALS AND METHODS: We searched MEDLINE (PubMed) in addition to MHS conference abstracts and websites, bibliographies of relevant published articles and https://clinicaltrials.gov/.

RESULTS: Multiple studies in U.S., U.K., and European military service members have noted medically attended and patient reported post-acute sequelae and symptoms across the domains of cardiorespiratory, neurocognitive, and mental health. Studies have also noted an association with SARS-CoV-2 infection and fitness in young adult service members, but the ongoing prevalence, morbidity, and functional impact of Long COVID in military populations in the current era remains unclear. All identified studies have limitations.

CONCLUSIONS: Considerable research has been conducted to understand the risk of and risk factors associated with Long COVID in active duty, much in the earlier pandemic period. Future research priorities include establishing Long COVID definitions most relevant to active duty personnel and conducting studies to delineate, treat, and prevent Long COVID's impact on cognitive, cardiorespiratory, and overall health and fitness for duty. Many considerations in this review article may also apply to post-acute sequelae from other infectious diseases, which pose risks to military health and readiness, including future respiratory virus pandemics.},
}

@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 = {},
number = {},
pages = {},
doi = {10.1097/QCO.0000000000001139},
pmid = {40748012},
issn = {1473-6527},
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.},
}

@article {pmid40747935,
year = {2025},
author = {Yip, A and Yip, J and Tsui, Z and Chan, CA and Lam, CP and Ching, JL and Yip, RK and Smith, GD},
title = {Weathering the Double Storm-Resilience in Chinese Older Cancer Patients With Long COVID: A Qualitative Study.},
journal = {Journal of advanced nursing},
volume = {},
number = {},
pages = {},
doi = {10.1111/jan.70106},
pmid = {40747935},
issn = {1365-2648},
support = {//This research was funded by the Institutional Development Grant (IDG) from Saint Francis University (Reference no: IDGP240211)./ ; },
abstract = {AIM: To explore the lived experiences of Chinese older adult cancer patients in Hong Kong navigating the challenges of long COVID.

DESIGN: A descriptive phenomenological study.

METHODS: Semi-structured interviews were conducted with 27 purposively sampled older Chinese cancer survivors in Hong Kong between January 2023 and January 2024. Data were analysed using Colaizzi's thematic analysis method.

RESULTS: Four key themes emerged: (1) the invisible scars of COVID-19: unrecognised and diverse symptoms; (2) the double-edged sword of protection: shielding from COVID-19 while battling cancer and long COVID; (3) forging strength in the crucible: adapting and thriving with cancer and long COVID and (4) nurturing resilience: the integral role of nursing in supporting cancer patients with long COVID during a pandemic.

CONCLUSION: Older Chinese cancer patients with long COVID experience a dual burden of unrecognised physical symptoms and profound psychological distress from isolation. Despite this, they demonstrate remarkable resilience, a process that can be actively supported through specialised nursing care.

ORIGINALITY/NOVELTY: This study offers original contributions to the limited literature on the intersection of cancer, long COVID, and ageing. It provides in-depth insights into the lived experiences of this vulnerable population, highlighting the diversity of long COVID symptoms, the psychological impact of pandemic-related precautions, and the crucial role of nursing in fostering resilience.

IMPACT: This study highlights the urgent need for nurses to recognise the unique challenges of this population. It provides a foundation for developing nurse-led, resilience-focused interventions that integrate tailored education, emotional support, and resource navigation into oncology care. These findings can inform practice and policy to better support the well-being of a vulnerable and growing patient demographic.

REPORTING METHOD: The study adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist.

No patient or public contribution.},
}

@article {pmid40746934,
year = {2025},
author = {Frediani, MM and Ribeiro, HS and Busatto, GF and Carvalho, CRR and Burdmann, EA},
title = {Renal Long COVID: A Scoping Review.},
journal = {Kidney medicine},
volume = {7},
number = {8},
pages = {101039},
pmid = {40746934},
issn = {2590-0595},
abstract = {RATIONALE & OBJECTIVE: Whether long coronavirus disease (long COVID) affects the kidneys remains to be understood. In this scoping review, we described the evidence of renal long COVID.

STUDY DESIGN: A scoping review was conducted according to the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines by searching MEDLINE, Embase, and other databases from inception until February 2025.

We included evidence on kidney-related outcomes in adult survivors of coronavirus disease 2019 (COVID-19) with data on long COVID.

Cohorts from all settings.

DATA EXTRACTION: We extracted data related to longitudinal kidney outcomes.

ANALYTICAL APPROACH: Data were synthesized and presented in tables and figures.

RESULTS: We screened 6,203 studies and included 37 in this review (38 reports), comprising 1,308,265 individuals with follow-up data. The majority were retrospective (61%) and from Europe (37%). All reports included hospitalized patients and 34% also included the community setting. Acute kidney injury (AKI) during acute COVID-19 phase was assessed in 58% of the reports. Chronic kidney disease (CKD) development was assessed in 29% of the reports, with wide variation in its frequency, ranging from 0.4%-45%. Progression of CKD (7 studies, 18%) ranged from 8%-49%. Studies reporting higher frequencies of AKI found larger rates of renal long COVID. Overall, there was high heterogeneity in how kidney-related outcomes were reported during follow-up. Most studies presented data on crude kidney function biomarkers (eg, serum creatinine or estimated glomerular filtration rate), while a few (13%) reported major adverse kidney events. Data on proteinuria or urinary biomarkers were scarce.

LIMITATIONS: Lack of studies with pre-COVID-19 data.

CONCLUSIONS: This scoping review highlighted that renal long COVID, characterized by CKD development and/or progression, may occur. Available evidence suggests that AKI may be associated with renal long COVID. Therefore, long-term kidney function monitoring is advisable after COVID-19 recovery to enable early diagnosis and timely intervention for CKD.},
}

@article {pmid40746715,
year = {2025},
author = {Shani, M and Wübbelt, K},
title = {Coping with long-COVID stigma: The role of self-compassion and self-coldness.},
journal = {Health psychology open},
volume = {12},
number = {},
pages = {20551029251349409},
pmid = {40746715},
issn = {2055-1029},
abstract = {Long COVID has been associated with stigmatization, prompting exploration of coping mechanisms. This cross-sectional study examined whether self-compassion and self-coldness mediate long-COVID stigma's effects on well-being. We surveyed 201 German adults with long-COVID (89% female; M age = 43.27, SD = 10.57). Most were officially diagnosed (88%), and 93% still experienced long-COVID symptoms at the time of survey. Measures included stigma, self-compassion, self-coldness, subjective well-being (SWB), and flourishing. Long-COVID stigma negatively correlated with SWB and flourishing. Higher self-compassion and lower self-coldness predicted better outcomes. Internalized stigma predicted lower flourishing through decreased self-compassion and increased self-coldness. In contrast, enacted stigma was associated with higher SWB and flourishing through lower self-coldness. Overall, mediation effects via self-coldness were significantly stronger than those via self-compassion, particularly in flourishing. These findings highlight the interplay between stigma, self-relating, and well-being, indicating both adaptive and maladaptive pathways. Interventions promoting self-compassion and reducing self-coldness may support holistic long-COVID care.},
}

@article {pmid40744539,
year = {2025},
author = {Zhou, W and Larson, JL and Veliz, PT and Kitto, K and Smith, S},
title = {Profiles of long COVID symptoms and self-efficacy for self-management: A cross-sectional survey.},
journal = {Applied nursing research : ANR},
volume = {84},
number = {},
pages = {151968},
doi = {10.1016/j.apnr.2025.151968},
pmid = {40744539},
issn = {1532-8201},
mesh = {Humans ; *COVID-19/complications/psychology/therapy ; Cross-Sectional Studies ; *Self Efficacy ; Female ; Male ; Adult ; *Self-Management/psychology ; Middle Aged ; Surveys and Questionnaires ; Aged ; SARS-CoV-2 ; *Self Care ; },
abstract = {BACKGROUND: Some patients with COVID-19 experience prolonged symptoms, known as long COVID. Self-management promises to improve symptoms, but little is known about the role of self-efficacy for long COVID symptom management.

OBJECTIVES: To identify distinct subgroups of patients experiencing long-term post-COVID symptom burden, and to examine the association between the identified subgroups and self-efficacy for symptom management.

METHODS: A cross-sectional survey design with a convenience sampling approach. This study included 491 adults who reported experiencing long COVID symptoms. Symptoms (fatigue, dyspnea, sleep disturbance, anxiety), and self-efficacy for self-management (Self-Efficacy for Managing Chronic Disease (SEMCD) and PROMIS Self-Efficacy) were collected. Latent Profile Analysis (LPA) was used to identify profiles of adults with similar patterns of long COVID symptoms. Multinomial logistic regression was used to examine the association between self-efficacy for self-management and distinct profiles, controlling for socio-demographics and health-related characteristics. Participants' strategies to relieve COVID symptoms were collected via open-ended questions and analyzed using content analysis.

RESULTS: The mean age was 40.6 (SD = 14.1) years of age. We identified four profiles based on the long COVID symptom burden: "low burden," "medium burden with low depression," "medium burden with high depression," and "high burden." Participants with a higher score of SEMCD were less likely to be in Group 3 (medium burden with high depression) (RRR: 0.76, 95 % CI: 0.60-0.96, P = 0.024) and Group 4 (high burden) (RRR: 0.71, 95 % CI: 0.50-1.00, P = 0.049). Participants with a higher score on PROMIS Self-Efficacy were less likely to be in Group 3 (RRR = 0.95, 95 % CI: 0.90-1.00, P = 0.047). Participants used a range of wellness activities and self-medication strategies to self-manage symptoms.

CONCLUSION: Patients with long COVID had four distinct symptom profiles. Greater self-efficacy was associated with the profiles of less symptom burden. Self-efficacy for self-management could be an important target to consider when developing interventions to improve symptom self-management and reduce long COVID symptom burden.},
}

Humans
*COVID-19/complications/psychology/therapy
Cross-Sectional Studies
*Self Efficacy
Female
Male
Adult
*Self-Management/psychology
Middle Aged
Surveys and Questionnaires
Aged
SARS-CoV-2
*Self Care

@article {pmid40744071,
year = {2025},
author = {Mughal, S and Andújar-Sánchez, F and Sabater-Arcis, M and Garrabou, G and Fernández-Solà, J and Alegre-Martin, J and Sanmartin Sentañes, R and Castro-Marrero, J and Esteve-Codina, A and Casals, E and Fernández-Costa, JM and Ramón-Azcón, J},
title = {Metabolic adaptation and fragility in healthy 3-D in vitro skeletal muscle tissues exposed to Chronic Fatigue Syndrome and Long COVID-19 sera.},
journal = {Biofabrication},
volume = {},
number = {},
pages = {},
doi = {10.1088/1758-5090/adf66c},
pmid = {40744071},
issn = {1758-5090},
abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID-19 (LC-19) are complex conditions with no diagnostic markers or consensus on disease progression. Despite extensive research, no in vitro model exists to study skeletal muscle wasting, peripheral fatigue, or potential therapies. We developed 3D in vitro skeletal muscle tissues to map muscle adaptations to patient sera over time. Short exposures (48 hours) to patient sera led to a significant reduction in muscle contractile strength. Transcriptomic analysis revealed the upregulation of glycolytic enzymes, disturbances in calcium homeostasis, hypertrophy, and mitochondrial hyperfusion. Structural analyses confirmed myotube hypertrophy and elevated mitochondrial oxygen consumption in ME/CFS. While muscles initially adapted by increasing glycolysis, prolonged exposure (96-144 hours) caused muscle fragility and fatigue, with mitochondria fragmenting into a toroidal conformation. We propose that skeletal muscle tissue in ME/CFS and Long COVID-19 progresses through a hypermetabolic state, leading to severe muscular and mitochondrial deterioration. This is the first study to suggest such transient metabolic adaptation. .},
}

@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 {pmid40740638,
year = {2025},
author = {Verduci, E and Risè, P and Fiore, G and Vizzuso, S and Bonomi, A and Dilillo, D and Fiori, L and Di Profio, E and Calcaterra, V and Mannarino, S and Zoia, E and D'Auria, E and Sala, A and Zuccotti, G},
title = {Exploratory study of the effect of DHA supplementation on blood fatty acids and inflammatory markers in children with MIS-C.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1597868},
pmid = {40740638},
issn = {2296-861X},
abstract = {BACKGROUND AND AIMS: Children infected with SARS-CoV-2 may develop multisystem inflammatory syndrome (MIS-C) 4-6 weeks after exposure. MIS-C is characterized by elevated markers of inflammation and low blood values of linoleic acid (LA), arachidonic acid (AA) and docosahexaenoic acid (DHA) during acute phase. The aim of this pilot exploratory study was to assess the short-term beneficial impact on the blood fatty acid profile following DHA supplementation in children who have suffered from MIS-C.

METHODS: Fifty-two children aged 2-18 years with diagnosed MIS-C, were enrolled between December '20 and March '22. Blood samples were collected at hospital discharge (T0), and at 3 (T1) and 6 months (T2) post-discharge using dried blood spots for fatty acid analysis by gas chromatography. Inflammatory and metabolic blood markers were assessed at T0 and T2. All participants received healthy dietary advice throughout the study. In Group 1 23 consecutive patients received DHA supplementation (250 mg/day of DHA) from T0 to T1, followed by dietary advice alone until T2. In Group 2 29 children with MIS-C received only dietary advice throughout the observation period.

RESULTS: An altered inflammatory status, independent of treatment, was shown in all children compared to pediatric reference values. After intervention, Group 1 experienced a significant enrichment in both total n-6 and n-3 blood FAs when compared to baseline (p < 0.0001). Specifically, there was a significant increase of DHA (1.19 ± 0.25 at T0 vs. 2.67 ± 0.78 at T1) and EPA (0.32 ± 0.09 at T0 vs. 0.46 ± 0.10 at T1) levels, that remained consistent at T2 (p = 0.0002 and p < 0.0001, respectively). Within Group 2 only n-3 alpha linolenic acid (ALA) significantly increased at T1 compared to baseline (p < 0.05). The total increase in n-3 after intervention (ΔT1-T0) was significantly higher in Group 1 compared to Group 2 [1.90(0.9) vs. 0.49(0.8), p < 0.0001 and p adj = 0.005]. Erythrocyte sedimentation rate (ESR) and IL-6 showed a better tendency toward normalization in Group 1, although without statistical significance.

CONCLUSION: This pilot study is the first to explore the potential effects of DHA supplementation in children with MIS-C. DHA was associated with improvements in the blood fatty acid profile, which persisted beyond the supplementation period, and showed a trend toward normalization of selected biochemical parameters. Further adequately powered, controlled studies are needed to confirm these observations and to evaluate the potential role of early n-3 PUFA supplementation during the stable and recovery phases in critically ill pediatric patients.},
}

@article {pmid40738888,
year = {2025},
author = {Alcalde-Herraiz, M and Iqbal, S and Wallin, JJ and Liu, Y and Nieves, W and Berry, M and Catala, M and Prieto-Alhambra, D and Xie, J},
title = {Sociodemographic factors, biomarkers and comorbidities associated with post-acute COVID-19 sequelae in UK Biobank.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {7009},
doi = {10.1038/s41467-025-62354-0},
pmid = {40738888},
issn = {2041-1723},
support = {SRF-2018-11-ST2-004).//DH | NIHR | Health Services and Delivery Research Programme (HS&DR Programme)/ ; },
mesh = {Humans ; *COVID-19/epidemiology/complications/blood ; Male ; Female ; United Kingdom/epidemiology ; Middle Aged ; Biomarkers/blood ; Biological Specimen Banks ; Comorbidity ; Case-Control Studies ; Aged ; SARS-CoV-2/isolation & purification ; Adult ; Post-Acute COVID-19 Syndrome ; Sociodemographic Factors ; Risk Factors ; UK Biobank ; },
abstract = {Long-term sequelae of COVID-19 remain critical public health concerns, with limited therapeutic options available. We conducted two case-control studies among COVID-19 infected individuals in the UK Biobank to explore the association of sociodemographic factors, clinical biomarkers, and comorbidities with the risk of two key phenotypes: Long COVID (LC, defined by patient self-report symptoms) and post-acute complications of SARS-CoV-2 infection (PACS, defined by clinical diagnosis), separately. Our study included 8,668 participants in the LC cohort (32% classified as cases) and 108,407 in the PACS cohort (with 2% being cases). Findings showed that age and sex were associated with both LC and PACS but in opposite directions. Additionally, obesity, socioeconomic deprivation, elevated C-reactive protein, triglyceride, vitamin D, HbA1c, cystatin C, urate, and alanine aminotransferase, and decreased HDL cholesterol and IGF-1, as well as CKD and COPD, were associated with LC. Most of these factors were also significant for PACS, except for alanine aminotransferase and vitamin D. These findings have potential mechanistic implications for the distinction between LC and PACS and can guide clinical implementation of identifying high-risk groups for targeted vaccination or other public health mitigation strategies.},
}

Humans
*COVID-19/epidemiology/complications/blood
Male
Female
United Kingdom/epidemiology
Middle Aged
Biomarkers/blood
Biological Specimen Banks
Comorbidity
Case-Control Studies
Aged
SARS-CoV-2/isolation & purification
Adult
Post-Acute COVID-19 Syndrome
Sociodemographic Factors
Risk Factors
UK Biobank

@article {pmid40738768,
year = {2025},
author = {Lemogne, C and Verduzco-Gutierrez, M and Burton, C},
title = {Integrative approaches to the understanding and treatment of long COVID syndrome.},
journal = {Journal of psychosomatic research},
volume = {},
number = {},
pages = {112334},
doi = {10.1016/j.jpsychores.2025.112334},
pmid = {40738768},
issn = {1879-1360},
}

@article {pmid40738266,
year = {2025},
author = {Rubin, LH and Shi, W and Azola, A and Bhattacharyya, A and Dastgheyb, RM and Wu, J and Penna, CD and Parker, H and Santiuste, I and Ehrenspeck, A and Coughlin, JM and Vannorsdall, TD and Lu, H and Veenhuis, R},
title = {Blood-Brain barrier disruption in long COVID and cognitive correlates: A cross-sectional MRI study.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bbi.2025.07.024},
pmid = {40738266},
issn = {1090-2139},
abstract = {Disruption of the blood-brain barrier (BBB) may contribute to neuropsychiatric symptoms observed in Long COVID (LC). Using a non-contrast magnetic resonance imaging (MRI) technique, we investigated BBB permeability in individuals with LC and its relationship to cognitive function. We hypothesized that LC individuals would show greater BBB permeability than recovered individuals, and that higher permeability would correlate with poorer cognition. Ninety-seven participants meeting the 2024 NASEM definition of LC with at least one neuropsychiatric symptom and 31 recovered controls completed an MRI scan and cognitive testing. BBB permeability was assessed using water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) MRI, which estimates the permeability-surface-area product (PS) of arterially labeled water entering the brain. Cognitive performance was summarized into eight factor scores derived from principal components analysis. Compared to controls, the LC group was older (M = 47 vs. 39 years, P = 0.003), less educated (P = 0.02), more likely female (P = 0.04), and had higher hospitalization rates for COVID-19 (P = 0.02). PS was significantly elevated in the LC group after adjusting for age and sex (B = 18.59, SE = 6.11, β = 0.28, P = 0.003). No significant group differences were found in cerebral blood flow, extraction fraction (E), or brain volume. Within the LC group, higher PS was associated with poorer motor function, but not with other cognitive domains. These findings indicate subtle but persistent BBB disruption in LC individuals over two years post-infection, with a potential link to motor dysfunction. This supports prior evidence of BBB changes following severe COVID-19 and suggests that BBB integrity may be a long-term biomarker of neuropsychiatric complications in LC.},
}

@article {pmid40738238,
year = {2025},
author = {Maison, DP and Khadka, VS and Mohd-Ibrahim, I and Peluso, MJ and Henrich, TJ and Deng, Y and Gerschenson, M},
title = {Peripheral immune progression to long COVID is associated with mitochondrial gene transcription: A meta-analysis.},
journal = {Mitochondrion},
volume = {},
number = {},
pages = {102072},
doi = {10.1016/j.mito.2025.102072},
pmid = {40738238},
issn = {1872-8278},
abstract = {SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has led to millions of cases of Long COVID worldwide. Long COVID is a phenomenon characterized by persistent and debilitating mental and physical symptoms following acute infection. Despite ongoing research, trials, and considerable progress in understanding Long COVID, its exact causes remain only partially understood, with current hypotheses addressing specific aspects of the condition. We conducted one of the most comprehensive meta-analyses to date of all quality bulk RNA-seq studies worldwide from the COVID-19 pandemic and show significant mitochondrial transcript changes in the peripheral immune system of people with Long COVID, with unexpectedly low levels of intracellular viral RNA in Long COVID. This extensive analysis, which includes 26 studies and 1,272 individuals, shows that mononuclear cells, PBMC, and granulocytes from Long COVID patients exhibit significant alterations in mitochondrial genes and related processes. These findings likely represent the true transcriptomic landscape of Long COVID across diverse datasets, highlighting the long-lasting impacts of SARS-CoV-2 on peripheral immune function. In combination with other ex vivo and proteomics studies showing mitochondrial dysfunction, our results suggest critical new directions, such as the potential role of clonal hematopoiesis and infected seed cells. This work highlights the need for further investigation into the mechanisms underlying these immune changes and persistent symptoms in people with Long COVID. These findings will serve as a foundation for defining the paradigm underlying the biological mechanisms of Long COVID, driving research into the peripheral immune system, bone marrow, and mitochondria.},
}

@article {pmid40737552,
year = {2025},
author = {Kaur, U and Chakrabarti, SS},
title = {COVID-19 vaccine safety studies- the need for a third group for extended monitoring.},
journal = {Expert opinion on drug safety},
volume = {},
number = {},
pages = {},
doi = {10.1080/14740338.2025.2542249},
pmid = {40737552},
issn = {1744-764X},
abstract = {INTRODUCTION: Studies assessing COVID-19 vaccine effectiveness have generally categorized individuals into 'vaccinated' and 'unvaccinated' groups. Long-term safety studies are sparse and have usually compared adverse events with background rates. Studies on timing of COVID-19 vaccination as a determinant of long COVID have provided variable results, while there is scarce data on timing of vaccination as a determinant of adverse events.

AREAS COVERED: We discuss some of our observations as well as the global evidence on the timing of COVID-19 vaccination as a determinant of long-COVID and adverse events. This special report is hypothesis-generating and aims to propose a conceptual framework and not establish causality.

EXPERT OPINION: We propose an alternative classification strategy for COVID-19 vaccinees, with special emphasis on individuals who received any dose of vaccination after recovering from natural COVID-19, i.e. the 'vaccine-after-COVID' (VAC) group. These individuals should be followed up for an extended period through multicentric and database studies. This may help in understanding the long-term safety of COVID-19 vaccines and the natural course of long COVID. Immunological characteristics of this group should also be scrutinized. The evidence gained might be useful in planning vaccination policies in the event of future pandemics.},
}

@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 {pmid40735347,
year = {2025},
author = {Hohberger, B and Ganslmayer, M and Harrer, T and Kruse, F and Maas, S and Borst, T and Heimke-Brinck, R and Stog, A and Knauer, T and Rühl, E and Zeisberg, V and Skornia, A and Bartsch, A and Ströbel, A and Wytopil, M and Merkel, C and Hofmann, S and Schmidt, KG and Lakatos, P and Schottenhamml, J and Herrmann, M and Mardin, C and Rech, J},
title = {Safety, tolerability and clinical effects of rovunaptabin, also known as BC007 on fatigue and quality of life in patients with Post-COVID syndrome (reCOVer): a prospective, exploratory, placebo-controlled, double-blind, randomised phase IIa clinical trial (RCT).},
journal = {EClinicalMedicine},
volume = {86},
number = {},
pages = {103358},
pmid = {40735347},
issn = {2589-5370},
abstract = {BACKGROUND: Rovunaptabin neutralises functional autoantibodies targeting G-Protein coupled receptors (GPCR-fAAbs), observed in patients with Post-COVID syndrome. As we hypothesise an improvement of PCS by rovunaptabin, the aim of reCOVer was to investigate safety, tolerability, and clinical effects of rovunaptabin in PCS patients.

METHODS: reCOVer is a prospective, exploratory, placebo-controlled, double-blind, randomised phase IIa clinical investigator initiated trial with 1350 mg rovunaptabin with additional cross-over at the Universitätsklinikum Erlangen, Germany. The trial was registered in EudraCT, 2022-001781-35. Screening was done between 21·11·2023 and 25·06·2024. Eligible participants (18-80 years) showed GPCR-fAAbs, at least 3/8 defined PCS symptoms persisting ≥3 months after COVID-19 and fatigue as major symptom. Participants were randomly assigned (1:1) to either receive rovunaptabin or placebo at day 0 (d0) and d48 with a follow-up of 28 days, respectively. Primary endpoint was the number of treatment emergent adverse events (TEAE) at d28 (co-primary endpoint: TEAE at d70); secondary endpoint focused on fatigue and quality of life.

FINDINGS: Thirty PCS patients were randomised and analysed. RCT analysis showed nine (rovunaptabin) and five TEAEs (placebo), yet without statistically significance (p = 0·1299; CI -14·80%; 63·02%); one serious adverse event, not related to treatment, was recorded. Rovunaptabin showed a neutralisation of GPCR-fAAb and a significant improvement of FACIT Fatigue Scale (effect size = 2·10, p = 0·0378), Bell score (effect size = 3·64, p = 0·0004), Fatigue Severity Scale (effect size = -2·66, p = 0·0088), and quality of life (4/8 items).

INTERPRETATION: As this proof-of-concept study showed effects on the patient-centred endpoint PCS and a good safety profil, subsequent studies are needed to confirm these results in a larger cohort.

FUNDING: German Federal Ministry of Education and Research, German Research Foundation.},
}

@article {pmid40734821,
year = {2025},
author = {Sandoval, A and Li, M and Jason, LA},
title = {Two neurocognitive domains identified for patients with myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of COVID-19.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1612548},
pmid = {40734821},
issn = {1664-2295},
abstract = {Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Acute Sequelae of COVID-19 (PASC) often have neurocognitive complaints that involve memory and concentration problems and difficulties paying attention. Other neurocognitive domains such as hypersensitivity to noise and light have rarely been included as aspects of neurocognitive impairment for these post-viral conditions. The current study evaluated a more extensive list of neurocognitive items for a group of 2,313 patients with ME/CFS and 299 patients with PASC. Exploratory factor analyses found two factors for each patient group, one involving classic memory and concentration symptoms and the other involving sensory overload phenomena. The findings suggest that researchers might consider expanding the types of self-report neurocognitive symptoms among patients with these post-viral illnesses.},
}

@article {pmid40734755,
year = {2025},
author = {Hupin, D and Pichot, V and Bäck, M and Nygren-Bonnier, M and Reistam, U and Runold, M and Bruchfeld, J and Dupré, C and Da Costa, A and Romeyer, C and Roche, F and Ståhlberg, M and Fedorowski, A and Nickander, J},
title = {Screening for postural orthostatic tachycardia syndrome using 24-hour electrocardiogram recording in patients with long coronavirus disease.},
journal = {Heart rhythm O2},
volume = {6},
number = {7},
pages = {949-955},
pmid = {40734755},
issn = {2666-5018},
abstract = {BACKGROUND: Cardiovascular autonomic dysfunction is a major complication in a large proportion of patients with long coronavirus disease (LC). As one of the most typical phenotypes of cardiovascular autonomic dysfunction, postural orthostatic tachycardia syndrome (POTS) is commonly observed as a sequelae of coronavirus disease infection.

OBJECTIVE: This study aimed to develop and test a 24-hour electrocardiogram (ECG) recording to direct the clinical suspicion toward the diagnosis of POTS.

METHODS: Consecutive patients referred to the Karolinska University Hospital in Stockholm from April 2021 to April 2022 were included. Patients with POTS were compared with patients with LC without POTS (verified by active standing tests) and control healthy subjects according to 3 specific analyses based on 24-hour ECG recording: (1) heart rate (HR) spikes of > 30 beats per minute, (2) awakening HR increase, and (3) HR variability (root mean square of successive difference). The control group consisted of healthy subjects from the database of the University Hospital of Saint-Etienne.

RESULTS: A total of 100 patients with LC (mean age, 42.54 ± 10.45 years; 92% women) and 100 healthy subjects (41.40 ± 7.21 years; 96% women) were included. LC POTS (n = 45) was associated with (1) a higher number of HR spikes/h (1.47 ± 0.84 vs 0.68 ± 0.50 and 0.40 ± 0.28/h; P < .01), (2) an abrupt and sustained increase in HR after awakening (P < .05), and (3) a reduction of HR variability: mean root mean square of successive difference of 34.90 ± 12.48 vs 30.47 ± 19.15 and 43.35 ± 21.10 ms (P < .01) compared with patients with LC without POTS (n = 55) and healthy subjects.

CONCLUSION: A triple analysis of 24-hour ECG recordings could reveal a characteristic POTS signature in LC. More research in other populations is needed to draw any firm conclusions about its generalizability.},
}

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

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

@article {pmid40730806,
year = {2025},
author = {Bunker, T and Horne, BD and Baldwin, MD and Sorrells, R and Turner, S and Laube, L and Solomon, A and Horne, LA and Novack, J},
title = {Intermittent fasting and a no-sugar diet for Long COVID symptoms: a randomized crossover trial.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27563},
doi = {10.1038/s41598-025-07461-0},
pmid = {40730806},
issn = {2045-2322},
mesh = {Humans ; *Fasting ; Male ; Female ; *COVID-19/diet therapy ; Cross-Over Studies ; Middle Aged ; Adult ; SARS-CoV-2 ; Aged ; Treatment Outcome ; Intermittent Fasting ; },
abstract = {Long COVID (LC) is a common chronic health condition that impairs daily functioning and social connections. This is the first randomized clinical trial to directly compare the effect of two Intermittent Fasting regimens on LC symptoms. The main objectives of this 10-week randomized cross-over trial are to compare the efficacy and safety of 4 weeks of 1-2 day fasting plus a restricted diet vs 4 weeks of mild time-restricted eating (TRE) and a restricted diet in reducing patient-reported LC symptoms. After a 2-week run-in, subjects were randomized to treatment A (TRE) or treatment B (Fasting) for 4 weeks. Subjects then crossed over to the other treatment for 4 weeks. The median fasting duration was 38 h (night-day-night), and the mean duration was 42 h. Symptoms were assessed via weekly online surveys. Primary outcomes were changes in LC symptom severity scores (LC-Scores) and in the number of LC symptoms (numLCsym) between treatments. Secondary outcomes were changes in LC-Scores and numLCsym over the 10-week trial. Fasting was superior to TRE alone in reducing LC-Scores (p = 0.008). The numLCsym decreased - 5.0 during the Fasting 4 weeks vs - 1.4 in the TRE 4 weeks (p = 0.002). Altogether, the 10-week regimen of a no-sugar diet, TRE and Fasting decreased the mean LC-Score by 51.8% (p < 0.0001) from 37.8 to 18.2. Similarly, numLCsym decreased from 20.5 to 12.2, a decrease of 40.6% (p < 0.0001). No major adverse safety events were recorded. Both intermittent fasting interventions decreased symptoms over the 10-week trial but the more intense fasting regimen was significantly better.Trial registration: ClinicalTrials.gov Identifier NCT06214455.},
}

Humans
*Fasting
Male
Female
*COVID-19/diet therapy
Cross-Over Studies
Middle Aged
Adult
SARS-CoV-2
Aged
Treatment Outcome
Intermittent Fasting

@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 {pmid40729248,
year = {2025},
author = {Carpallo-Porcar, B and Beamonte, EDC and Jiménez-Sánchez, C and Córdova-Alegre, P and Brandín-de la Cruz, N and Calvo, S},
title = {Multimodal Telerehabilitation in Post COVID-19 Condition Recovery: A Series of 12 Cases.},
journal = {Reports (MDPI)},
volume = {8},
number = {1},
pages = {},
doi = {10.3390/reports8010035},
pmid = {40729248},
issn = {2571-841X},
abstract = {Background: Post COVID-19 Condition is a recently recognized syndrome characterized by the persistence of various symptoms, including dyspnea, physical and mental fatigue, and post-exertional malaise. Currently, there is no established treatment or clear consensus on the effectiveness of rehabilitation, and given that patients could benefit from home-based rehabilitation, telerehabilitation, defined as remote rehabilitation using telematic systems, may be an option to reach more of the population with persistent COVID-19 symptoms. Therefore, it is necessary to show the efficacy of this telematic approach and the benefits of a multimodal rehabilitation strategy in these patients. Methods: Patients underwent home rehabilitation using a 12-week synchronous telerehabilitation system. The intervention included therapeutic education and physical and respiratory rehabilitation. The following variables were analyzed: Fatigue, quality of life, dyspnea, respiratory strength, aerobic capacity, and upper and lower limb strength. Conclusions: After 12 weeks, significant improvements were found in fatigue, aerobic capacity, and limb and respiratory strength. However, no improvement was found in dyspnea scores, which did not correlate with respiratory strength. Interestingly, a post-intervention correlation emerged between the distance covered in aerobic capacity and perceived fatigue, suggesting that asynchronous telerehabilitation could be a viable treatment strategy for these patients.},
}

@article {pmid40728641,
year = {2025},
author = {Daungsupawong, H and Wiwanitkit, V},
title = {Feasibility and acceptance of transdermal auricular vagus nerve stimulation using a TENS device in females suffering from long COVID fatigue: a comment.},
journal = {Wiener klinische Wochenschrift},
volume = {},
number = {},
pages = {},
pmid = {40728641},
issn = {1613-7671},
}

@article {pmid40727350,
year = {2025},
author = {Yao, Y and Liu, S and Zhang, Y and Liu, C and Shi, J and Chen, B and Yang, Z and Zhang, T and Li, Z and Gao, S},
title = {Case study of a 47-year-old long COVID patient diagnosed with Alzheimer's disease.},
journal = {Quantitative imaging in medicine and surgery},
volume = {15},
number = {7},
pages = {6535-6540},
pmid = {40727350},
issn = {2223-4292},
}

@article {pmid40726775,
year = {2025},
author = {Giménez-Orenga, K and Pierquin, J and Brunel, J and Charvet, B and Martín-Martínez, E and Lemarinier, M and Fried, S and Lucas, A and Perron, H and Oltra, E},
title = {Blood parameters differentiate post COVID-19 condition from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia.},
journal = {Brain, behavior, & immunity - health},
volume = {48},
number = {},
pages = {101058},
pmid = {40726775},
issn = {2666-3546},
abstract = {Post-COVID-19 condition, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM), are characterized by fatigue, pain, shortness of breath, sleep disturbances, cognitive dysfunction and other symptoms, heavily impacting on patients daily functioning. Moreover, over half of patients end up fulfilling ME/CFS and/or FM clinical criteria after a few months of SARS-CoV-2 infection. Expression of the toxic human endogenous retrovirus (HERV)-W ENV protein can be induced by viral infection and HERV-W detection was correlated with acute COVID-19 severity and found significantly expressed in post-COVID-19 condition. This study shows that HERV-W ENV may also be present in prepandemic cases of ME/CFS, FM or co-diagnosed with both clinical criteria, suggesting viral participation in these chronic diseases. To learn whether associated antiviral mechanisms may also show differing patterns of immunological responses, we measured IgM, IgG, IgA and IgE antibody isotypes against SARS-CoV-2 spike and nucleocapsid antigens, the levels of IL-6, IL-8, IL-10, IFNγ and TNFα cytokines, the level of NfL, a neural damage biomarker, as well as some blood cell markers potentially related with fatigue. Importantly, some of the measured variables showed a capacity to discriminate post-COVID-19 condition cases from all other participants, with 100 % sensitivity and up to 71.9 % specificity providing a new tool for a differential diagnosis between diseases or syndromes with so many overlapping clinical symptoms. Interestingly, the detected markers showed moderate-to-strong correlations with patient symptoms pointing at novel therapeutic opportunities.},
}

@article {pmid40725611,
year = {2025},
author = {Akiyama, H and Sakurada, Y and Honda, H and Matsuda, Y and Otsuka, Y and Tokumasu, K and Nakano, Y and Takase, R and Omura, D and Ueda, K and Otsuka, F},
title = {Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase.},
journal = {Journal of clinical medicine},
volume = {14},
number = {14},
pages = {},
doi = {10.3390/jcm14144918},
pmid = {40725611},
issn = {2077-0383},
support = {23fk0108585h0001//AMED/ ; Research Grant//Japanese Society of Hospital General Medicine/ ; },
abstract = {Background: Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist. Methods: In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated. Results: Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms. Conclusions: Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences.},
}

@article {pmid40725569,
year = {2025},
author = {Durak, G and Akin, K and Cetin, O and Uysal, E and Aktas, HE and Durak, U and Karkas, AY and Senkal, N and Savas, H and Tunaci, A and Medetalibeyoglu, A and Bagci, U and Erturk, SM},
title = {Radiologic and Clinical Correlates of Long-Term Post-COVID-19 Pulmonary Sequelae.},
journal = {Journal of clinical medicine},
volume = {14},
number = {14},
pages = {},
doi = {10.3390/jcm14144874},
pmid = {40725569},
issn = {2077-0383},
support = {R01-HL171376//Radiological Society of North America/ ; },
abstract = {Background/Objectives: The long-term sequelae of COVID-19 pneumonia, particularly the persistence of imaging abnormalities and their relationship to clinical symptoms, remain unclear. While the acute radiologic patterns are well-documented, the transition to chronic pulmonary changes-and their implications for long COVID symptoms-require systematic investigation. Methods: Our study included 93 patients with moderate to severe COVID-19 pneumonia who were admitted to Istanbul Medical Faculty Hospital, each having one follow-up CT scan over a ten-month period. Two thoracic radiologists independently calculated semi-quantitative initial chest CT scores to evaluate lung involvement in pneumonia (0-5 per lobe, total score 0-25). Two radiologists and one pulmonologist retrospectively examined the persistence of follow-up imaging findings, interpreting them alongside the relevant clinical and laboratory data. Additionally, in a subcohort (n = 46), mid-term (5-7 months) and long-term (≥10 months) scans were compared to assess temporal trajectories. Results: Among the 93 patients with long-term follow-up imaging, non-fibrotic changes persisted in 34 scans (36.6%), while fibrotic-like changes were observed in 70 scans (75.3%). The most common persistent non-fibrotic changes were heterogeneous attenuation (29%, n = 27) and ground-glass opacities (17.2%, n = 16), and the persistent fibrotic-like changes were pleuroparenchymal bands or linear atelectasis (58%, n = 54), fine reticulation (52.6%, n = 49), and subpleural curvilinear lines (34.4%, n = 32). Both persistent non-fibrotic and fibrotic-like changes were statistically correlated with the initial CT score (p < 0.001), LDH (p < 0.001), and ferritin levels (p = 0.008 and p = 0.003, respectively). Fatigue (p = 0.025) and chest pain (p < 0.001) were reported more frequently in patients with persistent non-fibrotic changes, while chest pain (p = 0.033) was reported more frequently among those with persistent fibrotic-like changes. Among the 46 patients who underwent both mid- and long-term follow-up imaging, 47.2% of those with non-fibrotic changes (17 out of 36) and 10% of those with fibrotic-like changes (4 out of 40) exhibited regression over the long term. Conclusions: Initial imaging and laboratory findings may indicate persistent imaging findings related to long-term sequelae of COVID-19 pneumonia. Many of these persistent imaging abnormalities, particularly non-fibrotic changes seen in the mid-term, tend to lessen over the long term. A correlation exists between persistent imaging findings and clinical outcomes of long COVID-19, underscoring the need for further research.},
}

@article {pmid40724994,
year = {2025},
author = {Hofmann, S and Lucio, M and Wallukat, G and Hoffmanns, J and Schröder, T and Raith, F and Szewczykowski, C and Skornia, A and Rech, J and Schottenhamml, J and Harrer, T and Ganslmayer, M and Mardin, C and Flecks, M and Lakatos, P and Hohberger, B},
title = {Functional Autoantibodies Targeting G-Protein-Coupled Receptors and Their Clinical Phenotype in Patients with Long-COVID.},
journal = {International journal of molecular sciences},
volume = {26},
number = {14},
pages = {},
doi = {10.3390/ijms26146746},
pmid = {40724994},
issn = {1422-0067},
support = {01EP2108A//German Federal Ministry of Research, Technology and Space (BMFTR): reCOVer/ ; 01EO2105//iIMMUNE_ACS/ ; 2490-PC-2021-V14//Bavarian Health and Food Safety Authority (LGL): discover/ ; },
mesh = {Humans ; *Autoantibodies/immunology/blood ; Male ; Female ; *Receptors, G-Protein-Coupled/immunology ; Middle Aged ; Adult ; *COVID-19/immunology ; Aged ; Phenotype ; SARS-CoV-2/immunology ; },
abstract = {Long-COVID (LC) is characterized by diverse and persistent symptoms, potentially mirroring different molecular pathways. Recent data might offer that one of them is mediated by functional autoantibodies (fAAb) targeting G protein-coupled receptors (GPCR). Thus, the aim of this study was to investigate the clinical phenotype of patients with LC in relation to their GPCR-fAAb seropositivity. The present study recruited 194 patients with LC and profiled them based on self-reported symptoms. GPCR-fAAb seropositivity was identified by using a cardiomyocyte bioassay, testing the presence and functionality of the AAbs. Logistic regression, clustering, and decision tree analyses were applied to examine associations between GPCR-fAAb profiles and self-reported symptoms considering age and gender. The most prevalent GPCR-fAAbs in patients with LC were fAAB targeting the β2 adrenergic receptor (β2-fAAb, 92.8%), the muscarinergic M2 receptor (M2-fAAb, 87.1%), the Angiotensin II type 1 receptor (AT1-fAAb, 85.6%), and angiotensin (1-7) Mas receptor (MAS-fAAb, 85.6%). β2-fAAb showed a significant relation with dizziness, lack of concentration, and POTS, while Endothelin Type A receptor functional autoantibody (ET-A-fAAb) was significantly related to deterioration of pre-existing neurological disorders. Statistical analysis indicated a strong positive correlation between M2- and β2-fAAb; as in addition, an association of β2-fAAb and gender was observed to one of the major clinical symptoms (fatigue/PEM), a critical impact of GPCR-fAAb on LC-pathogenesis can be assumed. Summing up, the present data show that specific GPCR-fAAb are associated with distinct clinical phenotypes. Especially, the combination of M2- and β2-fAAb seemed to be essential for the LC-phenotype with a combination of fatigue/PEM and lack of concentration as major clinical symptoms.},
}

Humans
*Autoantibodies/immunology/blood
Male
Female
*Receptors, G-Protein-Coupled/immunology
Middle Aged
Adult
*COVID-19/immunology
Aged
Phenotype
SARS-CoV-2/immunology

@article {pmid40724930,
year = {2025},
author = {Maiti, AK},
title = {In Silico Analysis of Post-COVID-19 Condition (PCC) Associated SNP rs9367106 Predicts the Molecular Basis of Abnormalities in the Lungs and Brain Functions.},
journal = {International journal of molecular sciences},
volume = {26},
number = {14},
pages = {},
doi = {10.3390/ijms26146680},
pmid = {40724930},
issn = {1422-0067},
abstract = {Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, p = 1.76 × 10[-10], OR = 1.63, 95% CI: 1.40-1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, LINC01276 and FOXP4-AS1, and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with FOXP4-AS1 and FOXP4, implying that this regulatory SNP could alter the normal cellular function of FOXP4-AS1 and FOXP4. Furthermore, rs9367106 is in eQTL with the FOXP4 gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent IFIH1/MDA5 activation, leading to suppression of host innate immune responses. LINC01276 targets the MED20 gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery.},
}

@article {pmid40724879,
year = {2025},
author = {Peppercorn, K and Sharma, S and Edgar, CD and Stockwell, PA and Rodger, EJ and Chatterjee, A and Tate, WP},
title = {Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients.},
journal = {International journal of molecular sciences},
volume = {26},
number = {14},
pages = {},
doi = {10.3390/ijms26146631},
pmid = {40724879},
issn = {1422-0067},
support = {no number//Brain Research New Zealand/ ; no number given//Brain Research New Zealand/ ; no number//ANZMES/ ; no numbers//Private donations/ ; },
mesh = {Humans ; *Fatigue Syndrome, Chronic/genetics/blood ; *DNA Methylation ; Male ; Female ; *COVID-19/genetics/blood ; Middle Aged ; Adult ; Leukocytes, Mononuclear/metabolism ; SARS-CoV-2 ; Epigenesis, Genetic ; Case-Control Studies ; Principal Component Analysis ; },
abstract = {Post-viral conditions, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC), share > 95% of their symptoms, but the connection between disturbances in their underlying molecular biology is unclear. This study investigates DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from patients with ME/CFS, LC, and healthy controls (HC). Reduced Representation Bisulphite Sequencing (RRBS) was applied to the DNA of age- and sex-matched cohorts: ME/CFS (n = 5), LC (n = 5), and HC (n = 5). The global DNA methylomes of the three cohorts were similar and spread equally across all chromosomes, except the sex chromosomes, but there were distinct minor changes in the exons of the disease cohorts towards more hypermethylation. A principal component analysis (PCA) analysing significant methylation changes (p < 0.05) separated the ME/CFS, LC, and HC cohorts into three distinct clusters. Analysis with a limit of >10% methylation difference and at p < 0.05 identified 214 Differentially Methylated Fragments (DMF) in ME/CFS, and 429 in LC compared to HC. Of these, 118 DMFs were common to both cohorts. Those in promoters and exons were mainly hypermethylated, with a minority hypomethylated. There were rarer examples with either no change in methylation in ME/CFS but a change in LC, or a methylation change in ME/CFS but in the opposite direction in LC. The differential methylation in a number of fragments was significantly greater in the LC cohort than in the ME/CFS cohort. Our data reveal a generally shared epigenetic makeup between ME/CFS and LC but with specific, distinct changes. Differences between the two cohorts likely reflect the stage of the disease from onset (LC 1 year vs. ME/CFS 12 years), but specific changes imposed by the SARS-CoV-2 virus in the case of the LC patients cannot be discounted. These findings provide a foundation for further studies with larger cohorts at the same disease stage and for functional analyses to establish clinical relevance.},
}

Humans
*Fatigue Syndrome, Chronic/genetics/blood
*DNA Methylation
Male
Female
*COVID-19/genetics/blood
Middle Aged
Adult
Leukocytes, Mononuclear/metabolism
SARS-CoV-2
Epigenesis, Genetic
Case-Control Studies
Principal Component Analysis

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

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

@article {pmid40723800,
year = {2025},
author = {Tobi, M and Chaudhari, D and Ryan, EP and Rossi, NF and Koka, O and Baxter, B and Tipton, M and Dutt, TS and Tobi, Y and McVicker, B and Angoa-Perez, M},
title = {Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia/Chronic Fatigue Syndrome (ME/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles.},
journal = {Biomolecules},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/biom15070928},
pmid = {40723800},
issn = {2218-273X},
support = {Merit Review Grant Awards (MT) and a Merit R&D #BX004127 (B.H.M. and M.T.)./VA/VA/United States ; },
abstract = {While there are many postulates for the etiology of post-viral chronic fatigue and other symptomatology, little is known. We draw on our past experience of these syndromes to devise means which can expose the primary players of this malady in terms of a panoply participating biomolecules and the state of the stool microbiome. Using databases established from a large dataset of patients at risk of colorectal cancer who were followed longitudinally over 3 decades, and a smaller database dedicated to building a Long PASC cohort (Post-Acute Sequelae of COVID-19), we were able to ascertain factors that predisposed patients to (and resulted in) significant changes in various biomarkers, i.e., the stool microbiome and serum cytokine levels, which we verified by collecting stool and serum samples. There were significant changes in the stool microbiome with an inversion from the usual Bacillota and Bacteroidota species. Serum cytokines showed significant differences in MIP-1β versus TARC (CC chemokine ligand 17) in patients with either PASC or COVID-19 (p < 0.02); IL10 versus IL-12p70a (p < 0.02); IL-1b versus IL-6 (p < 0.01); MCP1 versus TARC (p < 0.03); IL-8 versus TARC (p < 0.002); and Eotaxin3 versus TARC (p < 0.004) in PASC. Some changes were seen solely in COVID-19, including MDC versus MIP-1α (p < 0.01); TNF-α versus IL-1-β (p < 0.06); MCP4 versus TARC (p < 0.0001). We also show correlates with chronic fatigue where an etiology was not identified. These findings in patients with positive criteria for PASC show profound changes in the microbiome and serum cytokine expression. Patients with chronic fatigue without clear viral etiologies also have common associations, including a history of tonsillectomy, which evokes a likely immune etiology.},
}

@article {pmid40722688,
year = {2025},
author = {Ruas, CM and Silva, ML and Figueiredo, ALGF and Alencar, AP and Melo, SS and Castro, GF and Carobin, NV and Cordeiro, MA and Aguirre, JFR and Oliveira, AFM and Sabino, AP},
title = {Long COVID and Its Impacts: A Case-Control Study in Brazil.},
journal = {Biomedicines},
volume = {13},
number = {7},
pages = {},
doi = {10.3390/biomedicines13071615},
pmid = {40722688},
issn = {2227-9059},
support = {27968*17 - FINEP/RTR/PRPq/REDE COVID-19 - UFMG - LINBIO//MCTI/FINEP/ ; },
abstract = {Introduction: Long COVID, or post-COVID-19 syndrome, refers to a set of persistent symptoms following SARS-CoV-2 infection without another identifiable cause. Studies indicate that symptoms can last for up to two years and affect multiple body systems. Objective: The objective of this study is to compare symptom prevalence between infected individuals pre and post-COVID-19 and non-infected individuals in a population from Southeastern Brazil. Materials and Methods: A case-control study was conducted with participants from the MonitoraCovid program in a university in Brazil. The study included adults who responded to a questionnaire about long COVID symptoms. Data were collected virtually between October 2023 and May 2024. Results: Of the 2886 individuals eligible for analysis, 75.5% reported having been positive for COVID-19. Most participants were vaccinated, with 82.99% receiving two doses. In the pre and post comparison, individuals who had COVID-19 were more likely to report increased symptoms after infection, with 95.5% of assessed conditions worsening, particularly cognitive and respiratory issues. A comparison between those who had and had not been infected with COVID-19 showed that only 6.67% of symptoms were more prevalent in the infected group. The most significant post-COVID-19 symptoms included memory problems, fatigue, and shortness of breath, though some conditions, such as anxiety and sleep disturbances, were less common among those who had COVID-19. Conclusions: The findings reinforce that long COVID significantly impacts cognitive health, highlighting the importance of monitoring previously infected individuals. The study also emphasizes the need for further research in Global South contexts to better understand the long-term implications of COVID-19.},
}

@article {pmid40722521,
year = {2025},
author = {Krljanac, G and Asanin, M and Viduljevic, M and Stankovic, S and Simatovic, K and Lasica, R and Nedeljkovic-Arsenovic, O and Maksimovic, R and Zagorac, S and Savic-Radojevic, A and Djukic, T and Stevanovic, G and Pavlovic, V and Simic, T},
title = {Cardiovascular Manifestations of Patients with Long COVID.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/diagnostics15141771},
pmid = {40722521},
issn = {2075-4418},
abstract = {Background: This study investigates the potential mechanisms behind changes in cardiac structure and function in long COVID patients. Methods: This study involved 176 consecutive outpatients in follow-up care (average age 55.9 years; 58.5% male) who experienced symptoms for over 12 weeks (average 6.2 ± 2.7 months), following coronavirus infection (COVID-19). Results: The patients with long COVID and cardiovascular manifestations were significantly more hospitalized (88.5% vs. 75.9%) and had longer hospital stays. Significant echocardiography changes were observed in the left ventricular ejection fraction (LVEF) (59.6 ± 5.4% vs. 62.5 ± 3.8%); longitudinal strain (LS) in the sub-endocardium and intra-myocardium layers (-20.9 vs. -22.0% and -18.6 vs. -19.5%); circumferential strain (CS) in the sub-epicardium layers (-9.6 vs. -10.5%); and CS post-systolic shortening (CS PSS) (0.138 vs. 0.088 s). Additionally, pathological cardiac magnetic resonance (CMR) findings were seen in 58.2% of the group of patients with long COVID and cardiovascular manifestation; 43.3% exhibited positive late gadolinium enhancement (LGE), 21.0% had elevated native T1 mapping, and 22.4% had elevated native T2 mapping. Conclusions: Most patients with long COVID showed structural and functional changes in their cardiovascular systems, primarily caused by prolonged inflammation. Using multimodality imaging is important for uncovering the mechanisms to predict chronic myocarditis, early-stage heart failure, and pre-ischemic states, which can lead to serious complications. Recognizing the specific cardiovascular phenotypes associated with long COVID is essential in order to provide timely and appropriate treatment.},
}

@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 {pmid40729136,
year = {2024},
author = {Mosteanu, IM and Mahler, B and Parliteanu, OA and Stoichita, A and Matache, RS and Marghescu, AS and Filip, PV and Mota, E and Vladu, MI and Mota, M},
title = {Wedge Resection and Optimal Solutions for Invasive Pulmonary Fungal Infection and Long COVID Syndrome-A Case Report and Brief Literature Review.},
journal = {Reports (MDPI)},
volume = {7},
number = {2},
pages = {},
doi = {10.3390/reports7020025},
pmid = {40729136},
issn = {2571-841X},
abstract = {A rise in fungal infections has been observed worldwide among patients with extended hospital stays because of the severe infection caused by the new coronavirus pandemic. A 62-year-old female patient was admitted with a severe form of Coronavirus disease 2019 (COVID-19) and spent four weeks in the intensive care unit (ICU) requiring mechanical ventilation support before being moved to a tertiary hospital for further testing. Aspergillus fumigatus filamentous fungus, Candida spp., and positive bacteriology for multidrug-resistant Klebsiella pneumoniae and Proteus mirabilis were identified by bronchial aspirate cultures. The patient's progress was gradually encouraging while receiving oral antifungal and broad-spectrum antibiotic therapy along with respiratory physical therapy; but ultimately, thoracic surgery was necessary. Long-lasting tissue damage and severe, persistent inflammatory syndrome were the two main pathophysiological mechanisms that led to significant outcomes regarding lung lesions that were rapidly colonized by fungi and resistant flora, cardiac damage with sinus tachycardia at the slightest effort, and chronic inflammatory syndrome, which was characterized by marked asthenia, myalgias, and exercise intolerance.},
}

@article {pmid40721715,
year = {2025},
author = {Durieux, JC and Koberssy, Z and Daher, J and Baissary, J and Abboud, M and Atieh, O and Woolverton, C and McComsey, GA},
title = {Sex differences in inflammation and markers of gut integrity in long COVID.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27374},
pmid = {40721715},
issn = {2045-2322},
support = {UM1TR004528//Clinical and Translational Science Collaborative of Northern Ohio, funded by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health/ ; UM1TR004528//Clinical and Translational Science Collaborative of Northern Ohio, funded by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health/ ; },
abstract = {Endothelial damage represents an essential pathogenic mechanism of respiratory and multiorgan dysfunction as seen in the post-acute phase of COVID-19. Biological differences between male and female sex, inflammation, and gut integrity may have an integral role in endothelial damage and explain the residual effects of COVID-19 infection in long COVID, yet evidence is limited. Confirmed COVID-19 negative participants were 1:1 propensity-score matched to COVID-19 positive participants. Symptoms occurring at least one-month following COVID-infection and lasting more than three-months was defined as long COVID. Measures of endothelial function included reactive hyperemic index (RHI ≥ 1.67 = normal endothelial function) and augmentation index (higher AIx = worse arterial elasticity). A total of 89 COVID-19 negative participants was matched to 89 COVID-19 positive participants. Among the COVID-19 survivors, the median age was 42.92 years, 46.07% were female sex, and 57 (64%) had long COVID. Higher levels of inflammation (TNF-RI and oxLDL) and gut integrity (zonulin and BDG) was associated (P < 0.05) with a two-fold increase in the odds of long COVID. Female sex, independent of COVID-19 status, was 4x more likely to have worse AIx (P < 0.0001) compared to male sex. Among female sex with long COVID, higher levels of inflammation (IL-6, VCAM, hsCRP) and gut integrity (zonulin) was independently associated (P < 0.05) with higher AIx. Female sex with long COVID symptoms had the worse inflammation, gut integrity, and arterial stiffness among COVID-19 survivors. This reinforces the importance of continued, long-term follow-up care following COVID-19 infection, with special attention needed for female sex who may be at a higher cardiovascular disease risk.},
}

@article {pmid40721590,
year = {2025},
author = {Berry, M and Kong, AM and Paredes, R and Paone, J and Shah, R and Taylor, R and Mozaffari, E and Gupta, R and Gottlieb, RL and Mateu, L and Abdelghany, M and Goldman, JD and Chokkalingam, AP},
title = {Risk of Long COVID in hospitalized individuals treated with remdesivir for acute COVID-19.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27441},
doi = {10.1038/s41598-025-06052-3},
pmid = {40721590},
issn = {2045-2322},
abstract = {Long COVID comprises a multisystem syndrome occurring after COVID-19. This retrospective cohort study investigated whether remdesivir given during acute COVID-19 is associated with reduced incidence of Long COVID, including in immunocompromised subgroups. The HealthVerity database of hospital chargemaster data linked to closed claims was queried for patients aged ≥ 12 years hospitalized for ≥ 2 days with COVID-19 between May 1, 2020, and September 30, 2021. Relative risk between remdesivir-exposed and unexposed patients was calculated for 16 individual Long COVID outcomes and a composite of any Long COVID outcome, occurring 90-270 days after hospital admission. Subgroup analyses occurred in immunocompromised patients. Regression models accounted for censoring, competing risks, and treatment assignment weights; statistical inferences were adjusted for multiple comparisons. Among 3,661,303 hospitalized patients, 52,006 with COVID-19 were included; 20,246 (38.9%) were immunocompromised. In the overall and immunocompromised populations, respectively, 33.0% and 29.5% received remdesivir; the composite of ≥ 1 Long COVID outcome occurred in 55.5% and 62.9%. Patients administered remdesivir experienced lower risk of any Long COVID outcome (risk ratio, 0.96; 95% CI 0.94-0.97; adjusted P < 0.001). Risk for several individual Long COVID outcomes was lower in those receiving remdesivir in the overall and immunocompromised populations. In conclusion, exposure to remdesivir was associated with a lower risk of Long COVID.},
}

@article {pmid40721474,
year = {2025},
author = {Chong, KC and Wei, Y and Jia, KM and Boyer, C and Lin, G and Wang, H and Li, C and Hung, CT and Jiang, X and Yam, CHK and Chow, TY and Wang, Y and Zhao, S and Li, K and Yang, A and Mok, CKP and Hui, DS and Yeoh, EK and Guo, Z},
title = {SARS-CoV-2 rebound and post-acute mortality and hospitalization among patients admitted with COVID-19: cohort study.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6924},
doi = {10.1038/s41467-025-61737-7},
pmid = {40721474},
issn = {2041-1723},
abstract = {Recent investigations have demonstrated a relationship between the persistence of SARS-CoV-2 and post-COVID-19 conditions. Building upon a potential connection between SARS-CoV-2 persistence and early virologic rebound, we examine the association of early virologic rebound with post-acute mortality and hospitalization due to post-acute sequelae among hospitalized patients with COVID-19 in Hong Kong. Our study includes 13,859, 3959, and 4502 patients in the all-patient, nirmatrelvir/ritonavir, and molnupiravir group, respectively. Results show that patients who experienced virologic rebound exhibited a significantly higher risk of post-acute mortality (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.36-1.70) with a risk difference [RD] of 7.19%, compared with patients without virologic rebound. A similar increase in the risk of post-acute mortality is also observed in nirmatrelvir/ritonavir-treated patients (HR, 1.78; 95% CI, 1.41-2.25; RD, 12.55%) and molnupiravir-treated patients (HR, 1.47; 95% CI, 1.18-1.82; RD, 4.90%). The virologic rebound may thus serve as an early marker for post-COVID-19 condition, enabling healthcare officials to monitor and provide timely intervention for long COVID.},
}

@article {pmid40721458,
year = {2025},
author = {Meister, T and Maiväli, Ü and Tenson, K and Tisler, A and Kalda, R and Suija, K and Uusküla, A},
title = {Dynamic effects of COVID-19 vaccination on major acute cardiovascular events and mortality following SARS-CoV-2 infection in a target trial emulation study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27530},
doi = {10.1038/s41598-025-13043-x},
pmid = {40721458},
issn = {2045-2322},
abstract = {The COVID-19 pandemic presents significant health challenges, including increased risk of mortality and long-term complications. While vaccination has proven remarkably effective in mitigating severe disease and mortality associated with acute COVID-19 infection, the long-term implications of vaccination, particularly its influence on post-COVID cardiovascular events and the temporal dynamics of such effects, remain poorly understood. This target trial emulation study utilizes real-world electronic medical record data from April 2021 to March 2023 to address this gap. We evaluate the effect of pre-infection COVID-19 vaccination on the risk of major acute cardiovascular events (MACE) and all-cause mortality in individuals aged 40-85 years during one year after SARS-CoV-2 infection. Among individuals with COVID-19 (n = 18,223 vaccinated, n = 15,331 not vaccinated), vaccination provided a significant protective effect against MACE (weighted incidence rate ratio [wIRR] 0.71, 95% CI 0.58-0.84) and all-cause mortality (wIRR 0.32, 95% CI 0.28-0.36). This effect persisted for approximately three months after the acute infection. These findings underscore the importance of COVID-19 vaccination in reducing both short-term and long-term health risks associated with the infection.},
}

@article {pmid40721391,
year = {2025},
author = {Shi, L and Tian, X and Lu, X and Yih, B and Chen, J},
title = {Frailty in Alzheimer's disease: A bibliometric analysis of research hotspots, emerging trends, and knowledge structure.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877251362665},
doi = {10.1177/13872877251362665},
pmid = {40721391},
issn = {1875-8908},
abstract = {BackgroundFrailty has emerged as a major public health concern in aging populations, particularly among individuals with Alzheimer's disease (AD), where it exacerbates adverse outcomes and signals dementia progression. While research on frailty in AD has grown rapidly, a thorough analysis of key research hotspots and trends remains insufficient.ObjectiveThis study employs bibliometric methods to systematically explore core themes, identify potential frontiers and emerging directions in this field.MethodsOn December 27, 2024, a comprehensive search was conducted in the Web of Science Core Collection (WoSCC) database using keywords associated with frailty in AD. Bibliometric and knowledge mapping analyses were carried out using CiteSpace, VOSviewer, and R software.ResultsBetween 2005 and 2024, a total of 915 publications on frailty in AD were produced by 5950 researchers from 2084 institutions spanning 70 countries. Recent research in this field predominantly focuses on disciplines such as molecular biology, neuroscience, and pharmacology. Current studies emphasize interventions for frailty in patients with AD and the investigation of underlying pathological mechanisms, particularly concerning nutritional status and the influence of long COVID on frailty in AD. Emerging research themes include intervention strategies, mouse models, effects of long COVID, nutritional factors, mechanistic studies, brain fog, and subjective cognitive decline.ConclusionsThis bibliometric analysis highlights research frontiers on frailty in AD, emphasizing early monitoring and management of frailty are pivotal approaches to decelerate AD progression and improve patient outcomes. These findings offer valuable insights for future research, helping to address critical needs in patient care and disease management.},
}

@article {pmid40720834,
year = {2025},
author = {Feldman, CH and Santacroce, L and Bassett, IV and Thaweethai, T and Alicic, R and Atchley-Challenner, R and Chung, A and Goldberg, MP and Horowitz, CR and Jacobson, KB and Kelly, JD and Knight, S and Lutrick, K and Mudumbi, P and Parthasarathy, S and Prendergast, H and Quintana, Y and Sharareh, N and Shellito, J and Sherif, ZA and Taylor, BD and Taylor, E and Tsevat, J and Wiley, Z and Williams, NJ and Yee, L and Aponte-Soto, L and Baissary, J and Berry, J and Charney, AW and Costantine, MM and Duven, AM and Erdmann, N and Ernst, KC and Feuerriegel, EM and Flaherman, VJ and Go, M and Hawkins, K and Jacoby, V and John, J and Kelly, S and Kindred, E and Laiyemo, A and Levitan, EB and Levy, BD and Logue, JK and Marathe, JG and Martin, JN and McComsey, GA and Metz, TD and Minor, T and Montgomery, AP and Mullington, JM and Ofotokun, I and Okumura, MJ and Peluso, MJ and Pogreba-Brown, K and Raissy, H and Rosas, JM and Singh, U and VanWagoner, T and Clark, CR and Karlson, EW},
title = {Social Determinants of Health and Risk for Long COVID in the U.S. RECOVER-Adult Cohort.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-24-01971},
pmid = {40720834},
issn = {1539-3704},
abstract = {BACKGROUND: Social determinants of health (SDoH) contribute to disparities in SARS-CoV-2 infection, but their associations with long COVID are unknown.

OBJECTIVE: To determine associations between SDoH at the time of SARS-CoV-2 infection and risk for long COVID.

DESIGN: Prospective observational cohort study.

SETTING: 33 states plus Washington, DC, and Puerto Rico.

PARTICIPANTS: Adults (aged ≥18 years) enrolled in RECOVER-Adult (Researching COVID to Enhance Recovery) between October 2021 and November 2023 who were within 30 days of SARS-CoV-2 infection; completed baseline SDoH, comorbidity, and pregnancy questionnaires; and were followed prospectively.

MEASUREMENTS: Social risk factors from SDoH baseline questionnaires, ZIP code poverty and household crowding measures, and a weighted score of 11 or higher on the Long COVID Research Index 6 months after infection.

RESULTS: Among 3787 participants, 418 (11%) developed long COVID. After adjustment for demographic characteristics, pregnancy, disability, comorbidities, SARS-CoV-2 severity, and vaccinations, financial hardship (adjusted marginal risk ratio [ARR], 2.36 [95% CI, 1.97 to 2.91]), food insecurity (ARR, 2.36 [CI, 1.83 to 2.98]), less than a college education (ARR, 1.60 [CI, 1.30 to 1.97]), experiences of medical discrimination (ARR, 2.37 [CI, 1.94 to 2.83]), skipped medical care due to cost (ARR, 2.87 [CI, 2.22 to 3.70]), and lack of social support (ARR, 1.79 [CI, 1.50 to 2.17]) were associated with increased risk for long COVID. Living in ZIP codes with the highest (vs. lowest) household crowding was also associated with greater risk (ARR, 1.36 [CI, 1.05 to 1.71]).

LIMITATION: Selection bias may influence observed associations and generalizability.

CONCLUSION: Participants with social risk factors at the time of SARS-CoV-2 infection had greater risk for subsequent long COVID than those without. Future studies should determine whether social risk factor interventions mitigate long-term effects of SARS-CoV-2 infection.

PRIMARY FUNDING SOURCE: National Institutes of Health.},
}

@article {pmid40720313,
year = {2025},
author = {Andrejow, NW and Reidy, TG and Billups, K and Mougianis, ID and Birnie, KA and Ploetz, D and Carney, J},
title = {Adapting an Intensive Interdisciplinary Chronic Pain Rehabilitation Program to Address Long COVID in Youth: A Pilot Study.},
journal = {American journal of physical medicine & rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1097/PHM.0000000000002807},
pmid = {40720313},
issn = {1537-7385},
abstract = {During the COVID-19 pandemic, an established interdisciplinary pain program (IPP) pivoted to address the emerging needs of youth with Long COVID. The program used a rehabilitation model with an overarching goal of supporting youth in their return to school, activities of daily living, and social-emotional functioning by learning to cope with chronic pain and mitigate its impact on daily life. This paper describes that protocol and uses three patient cases to illustrate positive clinical changes in function and the lessons learned from adapting the IPP to pediatric patients with Long COVID.},
}

@article {pmid40717948,
year = {2025},
author = {Lapin, B and Baker, S and Thompson, N and Li, Y and Milinovich, A and Lago, W and Katzan, I},
title = {Pre-COVID health-related quality of life predicts symptoms and outcomes for patients with long COVID.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1581288},
doi = {10.3389/fpubh.2025.1581288},
pmid = {40717948},
issn = {2296-2565},
abstract = {BACKGROUND: Post-acute sequelae SARS-CoV-2 (PASC) is a prevalent condition with variable symptom presentation. PASC occurs more often with pre-existing medical conditions, however it is unknown whether pre-COVID health-related quality of life (HRQL) is associated with PASC. Similarly, the trajectory of HRQL following PASC is unknown.

OBJECTIVE: Our study sought to evaluate (1) whether pre-COVID HRQL is associated with PASC symptoms; (2) whether PASC patients have worse pre-COVID HRQL compared to matched controls; and (3) to compare HRQL trajectories from pre-COVID to 1-year follow-up between PASC patients and matched controls.

DESIGN: Retrospective cohort study with propensity-score matched control group.

PARTICIPANTS: The cohort included 1,114 adult patients (mean age 53 ± 14, 75% female) seen in a PASC clinic between 2/10/21 and 3/27/24 who completed HRQL surveys prior to their initial COVID-diagnosis in a large health system. A propensity-score matched control group included patients with COVID-19 without PASC.

MAIN MEASURES: HRQL was measured with PROMIS Global Health [global mental health (GMH) and global physical health (GPH) summary scores].

KEY RESULTS: PASC symptoms were significantly associated with pre-COVID HRQL. Symptoms most associated with PROMIS-GMH included diarrhea/nausea [odds ratio (OR) = 1.27 (95% CI: 1.16-1.39) per five-point worsening] and brain fog [OR = 1.25 (95% CI: 1.14-1.37)], while fatigue [OR = 1.39 (95% CI: 1.15-1.68)] had the highest association with PROMIS-GPH. Pre-COVID GMH and GPH were significantly worse for PASC patients compared to controls [-2.6 (SE 0.4) and -3.4 (0.3) T-score points, respectively]. At 1-year following COVID, PASC patients worsened significantly in GMH and GPH (-2.0 ± 8.2 and -1.2 ± 7.5 T-score points, respectively), compared to controls who worsened significantly on GMH but not GPH (-0.8 ± 7.7 and 0.2 ± 7.4 T-score points, respectively).

CONCLUSIONS: In patients with PASC, worse pre-COVID HRQL was associated with more PASC-related symptoms. PASC patients had worse pre-COVID HRQL compared to matched controls and experienced a greater decline in HRQL 1-year after COVID-diagnosis; however, this decline was below the threshold for clinical significance.},
}

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

@article {pmid40710029,
year = {2025},
author = {Yu, L and McCracken, LM},
title = {The Association Between COVID-19-Related Persistent Symptoms, Psychological Flexibility, and General Mental Health Among People With and Without Persistent Pain in the UK.},
journal = {Clinics and practice},
volume = {15},
number = {7},
pages = {},
pmid = {40710029},
issn = {2039-7275},
abstract = {Objectives: Persistent symptoms following COVID-19 may adversely impact the general mental health of people with chronic pain, and psychological flexibility may buffer these impacts. However, it remains unclear whether such lasting implications of COVID-19 differ between people with and without chronic pain. This study investigated the relationships between persistent symptoms post-COVID-19, psychological flexibility, and general mental health among people with and without persistent pain during the COVID-19 pandemic in the UK. Methods: A total of 204 adults living in the UK were recruited via social media and completed an online survey, including measures of persistent symptoms, depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), insomnia (the Insomnia Severity Index), and psychological flexibility (the Multidimensional Psychological Flexibility Inventory), and were included in the analyses. Results: Participants with persistent pain (n = 70) experienced more-persistent symptoms, poorer general mental health, and a higher level of psychological inflexibility compared with participants without persistent pain (n = 133). Overall, the relationships between persistent physical symptoms, general mental health, and psychological (in)flexibility showed similar patterns in the two groups. Participants with more-persistent physical symptoms experienced significantly poorer general mental health. Furthermore, people with higher levels of psychological inflexibility reported worse general mental health. There was little evidence that psychological (in)flexibility could "buffer" the association between persistent physical symptoms and general mental health. Conclusions: People with chronic pain appear more vulnerable to persistent symptoms and reduced general mental health compared with people without pain. Treatments that reduce psychological inflexibility, such as ACT, may improve outcomes for people with persistent symptoms post-COVID-19.},
}

@article {pmid40709992,
year = {2025},
author = {Crespo-Barrios, J},
title = {Vaxtherapy, a Multiphase Therapeutic Protocol Approach for Longvax, the COVID-19 Vaccine-Induced Disease: Spike Persistence as the Core Culprit and Its Downstream Effects.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {7},
pages = {},
doi = {10.3390/diseases13070204},
pmid = {40709992},
issn = {2079-9721},
abstract = {Background/Objectives: Chronic illness after COVID-19 vaccination (longvax) lacks a therapeutic protocol anchored in pathophysiology. Persistent vaccine derived spike protein appears to trigger microvascular fibrin amyloid microclots, immune dysfunction, pathogen reactivation and multisystem injury. This article proposes an integrative approach, Vaxtherapy, to tackle these mechanisms. Methods: A narrative synthesis of peer reviewed literature from 2021 to 2025 on spike related injury and vaccine adverse events was conducted, supplemented by clinical case series and mechanistic observations from long COVID. The findings were arranged into a four stage therapeutic sequence ordered by pathophysiological precedence. Results: Stage one aims to reopen hypoperfused tissue through oral fibrinolytics that degrade fibrin amyloid resistant microclots; stage two intends to neutralise circulating or tissue bound spike via a receptor binding domain monoclonal antibody cocktail; stage three seeks to eliminate reactivated viral or microbial reservoirs with targeted antivirals or antimicrobials once perfusion is improved; and stage four aspires to support tissue repair with mitochondrial supplements and, when indicated, cell based therapies. Omitting or reordering stages may reduce efficacy or foster resistance. Conclusions: This hypothesis driven framework outlines a biologically plausible roadmap for longvax research. By matching interventions to specific mechanisms (fibrinolysis, spike neutralisation, pathogen clearance and regeneration), it aims to guide controlled trials and compassionate pilot programs directed at durable recovery rather than chronic symptom management.},
}

@article {pmid40708634,
year = {2025},
author = {Aktaş, AR},
title = {Interaction of SARS-CoV-2 and SARS-CoV-2 vaccines with renin angiotensin aldosterone system, clinical outcomes, and angiotensin (1-7) as a physiological treatment recommendation: hypothesis and theory article.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1612442},
pmid = {40708634},
issn = {2296-858X},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected all of humanity since the first case was reported and spread rapidly around the world, creating a pandemic. Despite the repurposing of many drugs and the development of vaccines, effective treatment and protection are limited. In addition, SARS-CoV-2 continues to be a current public health problem with complications, identifying cases of long-term Covid syndrome, and detection of vaccine-related adverse events. It can be said that the most important factor underlying all these problems is that the interaction between SARS-CoV-2 and renin-angiotensin-aldosterone system (RAAS) is not completely understood despite extensive research. Although different disciplines have limited determinations from their own perspectives regarding the communication with RAAS, it has not been sufficiently expressed in a way to see the whole picture. In this study, it is tried to see the whole picture in the interaction of RAAS and SARS-CoV-2. It is detected inadequacies in treatments and interactions that may be design errors in vaccines. These determinations also show that our templates for producing treatments are not sufficient. For this reason, we have to develop our templates with what we have learned specifically about SARS-CoV-2. Considering the accuracy of our hypothesis on the SARS-CoV-2 - RAAS relationship, Ang(1-7) can be considered a strong option for treatment. Although the SARS-CoV-2 pandemic seems to be over, epidemics and even new pandemics are likely to occur with new mutations.},
}

@article {pmid40708533,
year = {2025},
author = {Chau, SWH and Chue, TM and Lam, TC and Lai, YL and Chan, RNY and Wong, PWC and Li, SX and Liu, Y and Chan, JWY and Chan, PK and Lai, CK and Leung, TWH and Wing, YK},
title = {Chronic post-COVID neuropsychiatric symptoms persisting more than 1 year after infection during the 'Omicron wave'.},
journal = {BJPsych open},
volume = {11},
number = {4},
pages = {e160},
doi = {10.1192/bjo.2025.10078},
pmid = {40708533},
issn = {2056-4724},
abstract = {BACKGROUND: The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.

AIMS: To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the 'Omicron wave' and discover phenotypes of patients based on their symptoms' patterns using a pre-registered protocol.

METHOD: We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.

RESULTS: Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint-fatigue and anxiety-depression) and a minor headache-dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint-fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint-fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.

CONCLUSIONS: Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.},
}

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

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

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

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

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

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

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

@article {pmid39656838,
year = {2024},
author = {Tenforde, MW and Reeves, EL and Weber, ZA and Tartof, SY and Klein, NP and Dascomb, K and DeSilva, MB and Yang, DH and Grannis, SJ and Irving, SA and Ong, TC and Link-Gelles, R and Salas, SB and Sy, LS and Lewin, B and Contreras, R and Zerbo, O and Fireman, B and Hansen, J and Timbol, J and Sheffield, T and Bride, D and Arndorfer, J and VanOtterloo, J and McEvoy, CE and Akinsete, OO and Essien, IJ and Dixon, BE and Rogerson, C and Fadel, WF and Duszynski, T and Naleway, AL and Barron, MA and Rao, S and Mayer, D and Chavez, C and Ball, SW and Payne, AB and Ray, C and Dickerson, M and Neelam, V and Adams, K and Flannery, B and DeCuir, J and Garg, S},
title = {Influenza vaccine effectiveness against hospitalizations and emergency department or urgent care encounters for children, adolescents, and adults during the 2023-2024 season, United States.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
pmid = {39656838},
issn = {1537-6591},
support = {CC999999/ImCDC/Intramural CDC HHS/United States ; },
abstract = {BACKGROUND: The 2023-2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses co-circulated. Seasonal influenza vaccine strains were well-matched to these viruses.

METHODS: Using health care encounters data from health systems in 8 states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023-April 2024. Using a test-negative design, we compared the odds of vaccination between patients with an acute respiratory illness (ARI) who tested positive (cases) versus negative (controls) for influenza by molecular assay, adjusting for confounders. VE was stratified by age group, influenza type (overall, influenza A, influenza B), and care setting (hospitalization, emergency department or urgent care [ED/UC] encounter).

RESULTS: Overall, 74,000 encounters in children and adolescents aged 6 months - 17 years (3,479 hospitalizations, 70,521 ED/UC encounters) and 267,606 in adults aged ≥18 years (66,828 hospitalizations, 200,778 ED/UC encounters) were included. Across care settings, among children and adolescents 15% (2,758/17,833) of cases versus 32% (18,240/56,167) of controls had received vaccination. Among adults, 25% (11,632/46,614) of cases versus 44% (97,811/220,992) of controls across care settings had received vaccination. VE was 58% (95% confidence interval [95% CI]: 44-69%) against hospitalization and 58% (95% CI: 56-60%) against ED/UC encounters for children and adolescents, and 39% (95% CI: 35-43) against hospitalization and 47% (95% CI: 46-49%) against ED/UC encounters for adults. Across age groups, VE was higher against influenza B than influenza A.

CONCLUSIONS: Influenza vaccines provided protection against influenza-associated illness across health care settings and age groups during the 2023-2024 influenza season.},
}

@article {pmid40705709,
year = {2025},
author = {Sauter, KA and Webb, GM and Bader, L and Kreklywich, CN and Takahashi, DL and Zaro, C and McGuire, CM and Lewis, AD and Colgin, LMA and Kirigiti, MA and Blomenkamp, H and Pessoa, C and Humkey, M and Hulahan, J and Sleeman, M and Zweig, RC and Thomas, S and Thomas, A and Gao, L and Hirsch, AJ and Levy, M and Cherry, S and Kahn, SE and Slifka, MK and Streblow, DN and Sacha, JB and Kievit, P and Roberts, CT},
title = {Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.},
journal = {PLoS pathogens},
volume = {21},
number = {7},
pages = {e1012988},
doi = {10.1371/journal.ppat.1012988},
pmid = {40705709},
issn = {1553-7374},
mesh = {Animals ; *COVID-19/complications/immunology/virology/pathology ; *Obesity/complications/immunology/virology ; Macaca mulatta ; Male ; *SARS-CoV-2/immunology ; Antibodies, Viral/blood/immunology ; Disease Models, Animal ; Post-Acute COVID-19 Syndrome ; Cytokines ; },
abstract = {Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.},
}

Animals
*COVID-19/complications/immunology/virology/pathology
*Obesity/complications/immunology/virology
Macaca mulatta
Male
*SARS-CoV-2/immunology
Antibodies, Viral/blood/immunology
Disease Models, Animal
Post-Acute COVID-19 Syndrome
Cytokines

@article {pmid40704727,
year = {2025},
author = {Yeh, AY and Chao, YY and Strauss, SM and Chou, CC},
title = {Association Between COVID-19 Infection and Subjective Cognitive Decline in Adults: A Cross-Sectional Online Survey Study.},
journal = {Western journal of nursing research},
volume = {},
number = {},
pages = {1939459251350812},
doi = {10.1177/01939459251350812},
pmid = {40704727},
issn = {1552-8456},
abstract = {BACKGROUND: Cognitive impairment is the most common residual symptom following COVID infection, reported in approximately 22% of adults diagnosed with COVID-19. Subjective cognitive decline is considered a significant early indicator of the progression of Alzheimer's disease. There is limited research investigating subjective cognitive decline following COVID-19 infection.

PURPOSE: The purpose of this study was to examine the relationship between COVID-19 infection and subjective cognitive decline in adults.

METHODS: In this comparative and cross-sectional study, data were collected via an online survey involving 98 adults diagnosed with COVID-19 and 317 adults never diagnosed with COVID-19. The mean age of participants was 30.2 ± 8.4 years, and 36.6% were female. The revised Everyday Cognition Scale was used to assess subjective cognitive decline. Data analysis included descriptive statistics, one-way analysis of covariance, and hierarchical multiple regression.

RESULTS: After controlling for covariates, adults diagnosed with COVID-19 experienced significantly greater subjective declines in memory (P = .002), language (P = .002), organizational ability (P = .03), attention (P = .003), and global cognition (P = .007) than those never diagnosed with COVID-19. Furthermore, COVID-19 diagnosis was a significant predictor of worse subjective declines in these domains of cognition.

CONCLUSION: Findings highlight the associations between COVID-19 infection and subjective cognitive decline across various domains. These results underscore the need for longitudinal studies to explore the progression of cognitive decline. Early detection and management of cognitive dysfunction can prevent further deterioration of cognitive function.},
}

@article {pmid40703523,
year = {2025},
author = {Girgis, AA and Cimbro, R and Yang, T and Rebman, AW and Sewell, T and Villegas de Flores, D and Vadalia, A and Robinson, WH and Cox, AL and Darrah, E and Soloski, MJ and Aucott, J},
title = {Aberrant T-cell phenotypes in a cohort of patients with post-treatment Lyme disease.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1607619},
pmid = {40703523},
issn = {1664-3224},
mesh = {Humans ; Female ; Male ; Middle Aged ; Adult ; Immunophenotyping ; Aged ; Phenotype ; Cytokines ; *Post-Lyme Disease Syndrome/immunology ; *Lyme Disease/immunology ; Cohort Studies ; *T-Lymphocyte Subsets/immunology/metabolism ; },
abstract = {Post-treatment Lyme Disease (PTLD) is a poorly understood complication of Borrelia burgdorferi infection with significant patient morbidity. Characterized by fatigue, generalized myalgias, and cognitive impairment, PTLD symptomatology closely resembles long COVID and other post-acute infection syndromes. While prior studies suggest immune dysregulation as a factor in PTLD pathogenesis, the mechanisms underlying its heterogeneous presentation and severity remain unclear. To associate symptom burden with discrete immune phenotypes, we applied factor analysis to self-reported symptom data from 272 PTLD patients to generate patient subgroups. We then immunophenotyped peripheral blood cells of these individuals and 28 healthy controls through 19-parameter flow cytometry and cytokine profiling to associate PTLD status and the newly defined subgroups with specific immune states. Our PTLD cohort had fewer circulating CXCR5+ CD4+ naïve T cells relative to healthy controls (5.2% vs. 8.3%, Padj < 0.001). These cells were positively associated with musculoskeletal pain in PTLD participants, but not healthy controls. This and additional immunophenotypic alterations, including an increased prevalence of CXCR3+ CCR4- CCR6- CD8 T cells (43.1% vs. 25.7%, Padj < 0.01), permitted the creation of an elastic net classifier which identified PTLD with moderate efficacy (AUC 0.83). Measurement of cytokines did not reveal associations with PTLD and did not improve the performance of the model. While we could not identify immune features which distinguished all patient subgroups, we did observe a female-specific increase in central memory CD8 T cells restricted to one high-fatigue patient subgroup. Additionally, factor analysis revealed multiple associations between immune cell frequency and the severity of specific symptoms. Collectively, our findings add to growing evidence of immune dysfunction as a prominent feature of PTLD.},
}

Humans
Female
Male
Middle Aged
Adult
Immunophenotyping
Aged
Phenotype
Cytokines
*Post-Lyme Disease Syndrome/immunology
*Lyme Disease/immunology
Cohort Studies
*T-Lymphocyte Subsets/immunology/metabolism

@article {pmid40703169,
year = {2025},
author = {Vu, TT and Hua, MJ and Dubois, C and Moskowitz, JT and Wallia, A and Hirschhorn, LR and Wilkins, JT and Evans, CT},
title = {Long COVID and its associations with burnout, anxiety, and depression among U. S. healthcare workers in the United States.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1582872},
pmid = {40703169},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Health Personnel/psychology/statistics & numerical data ; Male ; Female ; Adult ; *Anxiety/epidemiology ; *Burnout, Professional/epidemiology ; Cross-Sectional Studies ; *Depression/epidemiology ; Middle Aged ; United States/epidemiology ; Longitudinal Studies ; Surveys and Questionnaires ; SARS-CoV-2 ; Chicago/epidemiology ; },
abstract = {BACKGROUND: Data on Long COVID and its associations with burnout, anxiety and depression among healthcare workers (HCW) in the United States (U. S.) is limited.

METHODS: This study utilized cross-sectional data from the final survey conducted in July 2023, which was part of a longitudinal cohort study assessing COVID-19-related burnout and wellbeing among healthcare workers (HCWs) in a large tertiary academic healthcare system in the Chicago area. The survey included questions on self-reported Long COVID status, as well as the Oldenburg Burnout Inventory (OLBI) to measure burnout and the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CAT) to assess anxiety and depression. A total of 1,979 HCWs participated in the survey, yielding a response rate of 56.1%.

RESULTS: The analysis included 1,678 respondents with complete data, of whom 1,171 (70%) self-reported having had COVID-19. Of these, 90 (7.7%) reported Long COVID, with 53% indicating that their most bothersome symptoms persisted for more than 6 months, while 50% reported no longer experiencing those symptoms at the time of the survey. Multivariable linear regression analyses revealed that Long COVID was significantly associated with higher OLBI scores (β = 2.20, p = 0.004), PROMIS anxiety scores (β = 2.64, p = 0.001) and PROMIS depression scores (β = 1.98, p = 0.011) compared to those who had COVID-19 but not Long COVID. Similar patterns of associations were observed when comparing the Long COVID group to those who never had COVID-19. No significant differences were found between those who never had COVID-19 and those who had COVID-19 without developing Long COVID.

CONCLUSION: Long COVID was associated with higher levels of burnout, depression, and anxiety among healthcare workers compared to those who had COVID-19 alone or were never infected, despite its lower prevalence during the endemic phase. These findings underscore the need for continued prevention efforts and targeted support strategies in healthcare settings.},
}

Humans
*COVID-19/epidemiology/psychology
*Health Personnel/psychology/statistics & numerical data
Male
Female
Adult
*Anxiety/epidemiology
*Burnout, Professional/epidemiology
Cross-Sectional Studies
*Depression/epidemiology
Middle Aged
United States/epidemiology
Longitudinal Studies
Surveys and Questionnaires
SARS-CoV-2
Chicago/epidemiology

@article {pmid40702518,
year = {2025},
author = {Hadidchi, R and Patel, B and Madan, J and Liu, A and Henry, S and Duong, TQ},
title = {Elevated risk of new-onset chronic fatigue syndrome/myalgic encephalomyelitis up to four years after SARS-CoV-2 infection.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {815},
pmid = {40702518},
issn = {1479-5876},
mesh = {Humans ; *Fatigue Syndrome, Chronic/epidemiology/etiology ; *COVID-19/complications/epidemiology ; Female ; Male ; Middle Aged ; Retrospective Studies ; Adult ; *SARS-CoV-2 ; Risk Factors ; Incidence ; Aged ; Biomarkers/blood ; },
abstract = {BACKGROUND: Fatigue is a common sequela of SARS-CoV-2 infection, with many COVID-19 patients subsequently developing chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME). Long-term associations between COVID-19, new-onset CFS/ME, and other independent predictors such as vaccination for SARS-CoV-2, re-infection, and blood biomarkers at time of infection remain unclear. This study investigated the incidence and independent predictors of developing new-onset CFS/ME up to 4 years post SARS-CoV-2 infection in comparison to COVID- controls.

METHODS: This retrospective analysis conducted within the Montefiore Health System from February 1, 2020, to January 12, 2024 included adults without a prior diagnosis of fatigue or CFS/ME who were hospitalized for COVID-19 (n = 10,667), not hospitalized for COVID-19 (n = 25,409), and non-COVID-19 controls (n = 111,301). The observation time was between 30 days and 4 years post index date. The outcome was new-onset CFS/ME. Multivariate adjusted hazard ratios (HR) with 95% confidence intervals were calculated, assessing risk posed by SARS-CoV-2 infection, re-infection, and vaccination. Whether abnormal levels of aspartate aminotransferase, creatinine, D-dimer, lactate dehydrogenase, ferritin, hemoglobin, platelets, neutrophil/lymphocyte ratio, and temperature during hospitalization were associated with future CFS/ME risk was examined.

RESULTS: Compared to COVID- controls, the risk of developing new-onset CFS/ME was higher among both COVID-19 hospitalized (adjusted HR = 1.46 [1.07, 1.99]) and non-hospitalized patients (1.56 [1.25, 1.93]). Females (1.54 [1.27, 1.89]), patients with liver disease (1.61 [1.29, 2.00]), autoimmune disorders (1.57 [1.18, 2.08]), and anxiety disorders (1.35 [1.04, 1.74]) were more likely to develop CFS/ME (p < 0.05). Re-infection with SARS-CoV-2 was not associated with increased risk of incident CFS/ME. COVID-19 vaccination status during the initial phase of the rollout (prior to 2022) was associated with an increased risk of new-onset CFS/ME (p < 0.05). None of the blood biomarkers during acute COVID-19 were associated with new-onset CFS/ME risk (p > 0.05).

CONCLUSION: SARS-CoV-2 infection is associated with an increased risk of new-onset CFS/ME, independent of hospitalization status. Females, and individuals with autoimmune and anxiety disorders were more susceptible. These findings highlight the need for ongoing surveillance and management of fatigue-related symptoms in COVID-19 survivors.},
}

Humans
*Fatigue Syndrome, Chronic/epidemiology/etiology
*COVID-19/complications/epidemiology
Female
Male
Middle Aged
Retrospective Studies
Adult
*SARS-CoV-2
Risk Factors
Incidence
Aged
Biomarkers/blood

@article {pmid40700379,
year = {2025},
author = {Gottlieb, M and Spatz, ES and Yu, H and Ebna Mannan, I and Santangelo, M and Malicki, C and Gentile, NL and Geyer, RE and Charlton, A and Dyal, JW and Elmore, JG and Gatling, K and Hill, MJ and Montoy, JCC and O'Laughlin, KN and Rising, KL and Saydah, S and Stephens, KA and Wang, RC and Wisk, LE and Venkatesh, AK and Weinstein, RA and , },
title = {Effects of long COVID on healthcare utilization.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0327218},
doi = {10.1371/journal.pone.0327218},
pmid = {40700379},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Middle Aged ; *Patient Acceptance of Health Care/statistics & numerical data ; Adult ; Longitudinal Studies ; Prospective Studies ; Aged ; Hospitalization/statistics & numerical data ; SARS-CoV-2/isolation & purification ; United States/epidemiology ; Telemedicine ; Emergency Service, Hospital/statistics & numerical data ; },
abstract = {BACKGROUND: While most research on Long COVID (LC) has focused on symptoms and quality of life, there remains a critical need to better understand the effect of LC on resource utilization. This study sought to determine the type and amount of healthcare utilization among participants with versus without LC.

METHODS: This was a secondary analysis of a prospective, longitudinal, multicenter U.S. study of adult participants with symptomatic COVID-19, confirmed with testing, who completed 3-month post-infection surveys and had electronic health record data for at least 180 days pre- and post-index testing. We excluded participants with any COVID-19 infections within the 6 months following enrollment. Consistent with prior work, LC was defined as ≥3 post-infectious symptoms at 3 months, while those with <3 symptoms were categorized as not having LC. Our primary outcome was to compare the change in visit types between pre- and post-index testing (hospitalization, emergency department visit, office visit, procedure, telehealth, and other). As secondary outcomes, we assessed differences in visit complexity using the summative length of each encounter for each category as a measure of total healthcare usage.

RESULTS: A total of 847 participants met inclusion criteria (179 LC, 668 non-LC). When compared with the pre-index period, there was an overall increase in visit numbers of all six visit categories during the post-index period for all groups, most pronounced in office and telehealth visits. When compared with the non-LC group, the LC group was less likely to have ED visits (OR: 0.1; 95% CI 0.0-0.5). However, among those with LC who had at least one hospitalization, they were more likely to have additional hospitalizations (OR: 2.6; 95% CI 1.5-4.6). Visit length for office visits and hospitalization in the LC group was increased when compared with the non-LC group, though this diminished after adjustment for patient baseline characteristics.

CONCLUSIONS: All participants who were infected with SARS-CoV-2 had a marked increase in healthcare utilization during the subsequent 180 days. The LC group had significantly higher rates of additional hospitalization compared with those without LC, which may help to inform healthcare resource planning.},
}

Humans
*COVID-19/epidemiology
Female
Male
Middle Aged
*Patient Acceptance of Health Care/statistics & numerical data
Adult
Longitudinal Studies
Prospective Studies
Aged
Hospitalization/statistics & numerical data
SARS-CoV-2/isolation & purification
United States/epidemiology
Telemedicine
Emergency Service, Hospital/statistics & numerical data

@article {pmid40700078,
year = {2025},
author = {Kuliyeva, A and Serejnikova, N and Eshmotova, G and Teslya, Y and Ivina, A and Zarov, A and Panin, M and Prizov, A and Lyalina, V and Shestakov, D and Fayzullin, A and Timashev, P and Volkov, A},
title = {Post-COVID-19 Femoral Head Osteonecrosis Exhibits Mast Cell Clusters, Fibrosis, and Vascular Thrombosis: Key Pathological Mechanisms in Long COVID-19 Bone Degeneration.},
journal = {Pathophysiology : the official journal of the International Society for Pathophysiology},
volume = {32},
number = {3},
pages = {},
doi = {10.3390/pathophysiology32030036},
pmid = {40700078},
issn = {1873-149X},
support = {075-15-2024-658//the Ministry of Science and Higher Education of the Russian Federation/ ; },
abstract = {Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a common condition in hip surgery, which is characterized by the death of bone cells due to disruption of the blood supply and ultimately irreversible destruction of the hip joint. As a result of the COVID-19 pandemic, a significant increase in the incidence of ONFH has been identified. To better understand the pathogenesis of ONFH in the context of COVID-19, our research aimed to determine pathomorphological changes in articular tissues specific to post-COVID-19 ONFH. Methods: Using morphological, morphometric, and statistical methods, the femoral heads after hip arthroplasty were retrospectively studied in patients with post-COVID-19 ONFH (n = 41) compared to a non-COVID-19 group of patients (n = 47). Results: Our results revealed that the key morphofunctional biomarkers of post-COVID-19 ONFH were clusters of mast cells, extensive areas of fibrosis, numerous arterial and venous thrombi, and giant cell granulomas. The potential relationship of those morphological features with the action of the SARS-CoV-2 coronavirus was discussed. Conclusions: Mast cells have been proposed as the leading players that may trigger the main molecular and cellular mechanisms in the development of post-COVID-19 ONFH and can be considered a diagnostic sign of the disease.},
}

@article {pmid40699644,
year = {2025},
author = {Korobova, ZR and Arsentieva, NA and Liubimova, NE and Batsunov, OK and Butenko, AA and Kokoeva, AE and Kucherenko, NG and Kashchenko, VA and Boeva, EV and Norka, AO and Knizhnikova, AA and Rassokhin, VV and Belyakov, NA and Totolian, AA},
title = {B Cell Dynamics and Transitional B Cells in Long COVID.},
journal = {Current issues in molecular biology},
volume = {47},
number = {4},
pages = {},
doi = {10.3390/cimb47040245},
pmid = {40699644},
issn = {1467-3045},
support = {121030200299-3//Federal Service on Customers' Rights Protection and Human Well-Being Surveillance of Russia/ ; },
abstract = {BACKGROUND: Long COVID is characterized by persistent symptoms following acute SARS-CoV-2 infection. This study aims to evaluate immune system markers, including antigen-specific antibodies, B cell subsets, and Th2-related cytokines, in individuals with long COVID and to investigate their potential impact on the development of this condition.

METHODS: We analyzed blood plasma from 63 individuals diagnosed with long COVID based on clinical presentation and 47 healthy individuals with COVID-19 history but no clinical symptoms. Antigen-specific IgG antibodies were measured using commercial ELISA kits. Lymphocyte subpopulations were assessed via flow cytometry and a gating strategy based on CD27 and CD38. Th2 cytokines (IL-4, IL-5, IL-13) were quantified using the xMAP multiplex assay.

RESULTS: We noted no significant differences in IgG levels between groups. Notably, individuals with long COVID demonstrated a higher percentage of naive mature B cells (CD27-CD38+), while transitional (CD27-CD38+++) and double-negative (DN, CD27-CD38-) cells were significantly reduced. Elevated levels of IL-5 and IL-13 were observed in long COVID patients. Classification analysis revealed that the percentage of transitional B cells (CD27-CD38+++) was a strong predictor of long COVID.

CONCLUSIONS: Our findings highlight alterations in B cell dynamics among individuals with long COVID, which may contribute to autoimmune processes.},
}

@article {pmid40697636,
year = {2025},
author = {Welbel, R and Rutha, E and Ording, J and Wang, D and Hirschtick, J},
title = {The Effects of a Mindfulness-Based Intervention on Depression and Anxiety in the Long-COVID Population.},
journal = {Journal of patient-centered research and reviews},
volume = {12},
number = {3},
pages = {134-139},
pmid = {40697636},
issn = {2330-0698},
abstract = {Long-COVID is a complicated, post-viral syndrome involving multiple body systems and can present with neuropsychiatric symptoms. Little has been reported about the neuropsychiatric symptoms of long-COVID, and validated treatments do not yet exist. There is prior evidence that mindfulness-based strategies have been helpful for those with chronic illnesses; shown significant decreases in anxiety, stress, and depression; and enhanced quality of life. In this study, we report on the utility of a mindfulness-based intervention on levels of anxiety and depression in a long-COVID population. Our hospital system founded both a "Covid Recovery Clinic" (CRC) and a "Post-COVID Resilience Program" (PCRP). The PCRP consisted of a six-week virtual group therapy protocol that focused on mindfulness-based practices. Before and after the therapy intervention, participants answered questionnaires to capture depressive and anxiety symptoms. Pre- and post-questionnaire scores do not show a significant improvement in depressive or anxiety symptoms, although the study was limited by a small sample size. Further research is needed to investigate whether similar programs with a larger sample size can improve the mental health status of patients suffering from long-COVID.},
}

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

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

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

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

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

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

@article {pmid40696212,
year = {2025},
author = {Harsányi, L and Kincses, Z and Veselinović, M and Zehetner, J and Altorjay, Á},
title = {Five-year clinical outcomes of RefluxStop surgery in the treatment of acid reflux: a prospective multicenter trial of safety and effectiveness.},
journal = {Surgical endoscopy},
volume = {},
number = {},
pages = {},
pmid = {40696212},
issn = {1432-2218},
abstract = {INTRODUCTION: RefluxStop surgery corrects all three components of the anti-reflux barrier without affecting the food passageway. Long-term 5-year safety and effectiveness clinical outcomes are presented from the RefluxStop CE mark trial, used in an FDA PMA submission. This comprehensive and meticulously controlled data are, therefore, presented across multiple reports with other outcomes in a separate complementary article.

METHODS: A prospective, single-arm, multicenter clinical study was conducted to investigate RefluxStop surgery in 50 adults with chronic GERD, PPI use, GERD-HRQL score, 24-h pH testing, contrast-swallow x-ray, and serious/non-serious AEs presented.

RESULTS: Forty-four (n = 44) subjects completed 5-year follow-up, whereof 91% underwent pH testing and contrast-swallow x-ray. Three subjects were withdrawn due to COVID-19 (two deaths and one long-COVID), all well-treated beforehand, at 3-4 years. PPI usage (including COVID-19 subjects) in 1/47 (2.1%). The median (IQR) total GERD-HRQL score improved by 90% (72-98%) from a baseline of 29.5 (33.0-24.0) to 3.0 (0.5-7.5) at 5 years (p < 0.001) and 24-h pH monitoring results improved by 90.4% to a mean total acid exposure time (pH < 4) of 1.57% from 16.35% at baseline (p < 0.001). No cases (0%) of device explantation, migration/erosion, or esophageal dilatation occurred during the study. Five-year contrast-swallow x-ray showed zero (0%) dislocations, migrations, or re-herniations. Five subjects (n = 5) experienced serious AEs of which all were resolved. Only two procedure-related AEs occurred between 1 and 5 years, one moderate dyspepsia and one mild dysphagia, subsequently resolved.

CONCLUSION: The RefluxStop procedure demonstrated exceptional long-term 5-year outcomes. Only one subject took PPIs at follow-up. Both median GERD-HRQL scores and mean 24-h pH results improved by > 90% from baseline (p = 0.001). No device-related AEs, explantations, or migrations occurred during the 5-year study. Only two procedure-related AEs occurred between 1 and 5 years, one dyspepsia and one mild dysphagia (resolved). These objective and patient-reported results were robustly maintained from previously published 1- to 4-year data.},
}

@article {pmid40695836,
year = {2025},
author = {Coleon, A and Larrous, F and Kergoat, L and Tichit, M and Hardy, D and Obadia, T and Kornobis, E and Bourhy, H and de Melo, GD},
title = {Hamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6714},
pmid = {40695836},
issn = {2041-1723},
support = {ANRS MIE 202112015304//Fondation pour la Recherche Médicale (Foundation for Medical Research in France)/ ; PFR-4 - Long Covid//Institut Pasteur/ ; 2022-2023 Brain Axis SRA3 M2 Master Student Call//Institut Pasteur/ ; },
mesh = {Animals ; *COVID-19/genetics/virology/metabolism/pathology/complications/immunology ; *SARS-CoV-2/physiology/genetics ; Mesocricetus ; *Transcriptome ; *Brain Stem/virology/metabolism/pathology ; Cricetinae ; Disease Models, Animal ; Male ; Anxiety ; Humans ; Immunity, Innate/genetics ; *Neurodegenerative Diseases/genetics/virology ; Depression ; RNA, Viral ; },
abstract = {Following infection with SARS-CoV-2, patients may experience with one or more symptoms that appear or persist over time. Neurological symptoms associated with long COVID include anxiety, depression, and memory impairment. However, the exact underlying mechanisms are not yet fully understood. Using golden hamsters as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persistently infect the brain, as viral RNA and replicative virus are detected in the brainstem 80 days after the initial infection. Infected hamsters exhibit a neurodegenerative signature in the brainstem, characterized by overexpression of innate immunity genes, and altered expression of genes involved in the dopaminergic and glutamatergic synapses, in energy metabolism, and in proteostasis. These infected animals exhibit persistent depression-like behavior, impaired short-term memory, and late-onset signs of anxiety. Finally, we provide evidence that viral and immunometabolic mechanisms coexist in the brainstem of SARS-CoV-2-infected hamsters, contributing to the manifestation of neuropsychiatric and cognitive symptoms.},
}

Animals
*COVID-19/genetics/virology/metabolism/pathology/complications/immunology
*SARS-CoV-2/physiology/genetics
Mesocricetus
*Transcriptome
*Brain Stem/virology/metabolism/pathology
Cricetinae
Disease Models, Animal
Male
Anxiety
Humans
Immunity, Innate/genetics
*Neurodegenerative Diseases/genetics/virology
Depression
RNA, Viral

@article {pmid40694553,
year = {2025},
author = {Ma, KPK and Stober, T and Gottlieb, M and Geyer, RE and Rising, K and Saydah, S and Santangelo, M and Gatling, K and Grau, D and Wang, RC and Montoy, JC and Idris, A and MacDonald, S and Hill, MJ and Huebinger, R and Prado, MG and Gentile, NL and Spatz, E and Maliki, C and Dorney, J and Elmore, JG and L'Hommedieu, M and Weinstein, RA and Venkatesh, AK and Stephens, KA and , },
title = {Participant engagement in a national longitudinal study of COVID-19: Insights from the INSPIRE study.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0325948},
doi = {10.1371/journal.pone.0325948},
pmid = {40694553},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/psychology/virology ; Longitudinal Studies ; Male ; Female ; Middle Aged ; Adult ; Motivation ; United States/epidemiology ; Surveys and Questionnaires ; SARS-CoV-2/isolation & purification ; Aged ; *Patient Participation/psychology ; Registries ; },
abstract = {OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S.

METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data.

RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to learn with researchers about COVID-19. They expressed divided opinions about the relevance of INSPIRE research questions. They reported difficulties navigating the virtual research platform and the need for making survey participation less cognitively demanding. They sought more regular feedback on study findings.

CONCLUSIONS: Our findings offered insights into incorporating decentralized participatory methods in longitudinal research, strengthening reciprocal research communications, making virtual research platforms user-friendly, and employing strategies to reduce participants' cognitive burden in research.

POLICY IMPLICATIONS: Longitudinal studies should focus on optimizing these aspects of participant engagement to produce rigorous findings that inform policy and practice on lasting effects of COVID-19 including Long COVID.},
}

Humans
*COVID-19/epidemiology/psychology/virology
Longitudinal Studies
Male
Female
Middle Aged
Adult
Motivation
United States/epidemiology
Surveys and Questionnaires
SARS-CoV-2/isolation & purification
Aged
*Patient Participation/psychology
Registries

@article {pmid40694308,
year = {2025},
author = {Floridia, M and Weimer, LE and Rovere Querini, P and Bonfanti, P and Lacedonia, D and Figliozzi, S and Zucco, S and Andreozzi, P and Barisione, E and Lo Forte, A and Gnerre, P and Loso, K and Onder, G and , },
title = {Persistence of symptoms in long-COVID: follow-up trajectories of 30 symptoms in 755 patients from a national multicenter study from Italy.},
journal = {Internal and emergency medicine},
volume = {},
number = {},
pages = {},
pmid = {40694308},
issn = {1970-9366},
support = {I85F21003410005//Ministero della Salute/ ; },
abstract = {Aim of the study was to define the patterns and determinants of symptom persistence in Long-COVID. The study population was represented by a multicenter cohort of patients with persisting symptoms after SARS-CoV-2 infection. Data collection included demographics, comorbidities, characteristics of acute infection, vaccination, reinfection, plus 30 different symptoms. The associations between covariates and persistence were assessed in multivariable logistic regression models. The study evaluated, at a mean interval of 453 days from acute SARS-CoV-2 infection, symptom persistence in 755 patients who had Long-COVID symptoms at a mean interval of 223 days from COVID-19. At second evaluation, 423 (56.0%) patients still presented one or more symptoms and 332 (44.0%) were symptom free. In those who remained symptomatic, the mean number of symptoms significantly reduced between the two evaluations. Compared to the first evaluation, the overall mean symptom regression rate was 72%, with lower regression rates observed for dyspnea (53%), anxiety (54%) and sleep disturbances (55%). The risk of persistence was increased for female sex, higher BMI, hospitalization and stronger ventilatory support during acute disease, higher number of initial symptoms and particular comorbidities (anxiety, chronic pulmonary disease, asthma), and decreased with the increase of age and time from acute SARS-CoV-2 infection. Neither SARS-CoV-2 vaccination nor reinfection showed significant associations with persistence. In this case series, roughly half of the patients that were symptomatic 7 months after acute SARS-CoV-2 infection remained symptomatic after an additional 7 months. The pattern and predictors of persistence draw attention to certain particular risk factors and manifestations that tend to persist longer than others.},
}

@article {pmid40693778,
year = {2025},
author = {Song, Y and Mehl, F and Muehling, LM and Canderan, G and Enfield, K and Sun, J and Yin, MT and Ratcliffe, SJ and Wilson, JM and Kadl, A and Woodfolk, JA and Zeichner, SL},
title = {ACE-2-like enzymatic activity in COVID-19 convalescents with persistent pulmonary symptoms associated with immunoglobulin.},
journal = {mBio},
volume = {},
number = {},
pages = {e0173525},
doi = {10.1128/mbio.01735-25},
pmid = {40693778},
issn = {2150-7511},
abstract = {UNLABELLED: Many difficult-to-understand clinical features characterize COVID-19 and post-acute sequelae of COVID-19 (PASC or long COVID [LC]). These can include blood pressure instability, hyperinflammation, coagulopathies, and neuropsychiatric complaints. The pathogenesis of these features remains unclear. The SARS-CoV-2 Spike protein receptor-binding domain (RBD) binds angiotensin converting enzyme 2 (ACE2) on the surface of host cells to initiate infection. We hypothesized that some people convalescing from COVID-19 may produce anti-RBD antibodies that resemble ACE2 sufficiently to have ACE2-like catalytic activity, that is, they are ACE2-like proteolytic abzymes that may help mediate the pathogenesis of COVID-19 and LC. In previous work, we showed that some people with acute COVID-19 had immunoglobulin-associated ACE2-like proteolytic activity, suggesting that some people with COVID-19 indeed produced ACE2-like abzymes. However, it remained unknown whether ACE2-like abzymes were seen only in acute COVID-19 or whether ACE2-like abzymes could also be identified in people convalescing from COVID-19. Here, we show that some people convalescing from COVID-19 attending a clinic for people with persistent pulmonary symptoms also have ACE2-like abzymes and that the presence of ACE2-like catalytic activity correlates with alterations in blood pressure in an exercise test.

IMPORTANCE: Patients who have had COVID-19 can sometimes have troublesome symptoms, termed post-acute sequelae of COVID-19 (PASC) or long COVID (LC), which can include problems with blood pressure regulation, gastrointestinal problems, inflammation, blood clotting, and symptoms like "brain fog." The proximate causes for these problems are not known, which makes these problems difficult to treat definitively. We previously found that some acute COVID-19 patients make antibodies against SARS-CoV-2, the virus that causes COVID-19, that act like an enzyme, angiotensin converting enzyme 2 (ACE2). ACE2 normally helps regulate blood pressure and serves as the receptor for SARS-CoV-2 in the body. We show that patients convalescing from COVID-19 also make antibodies that act like ACE2 and that the presence of those antibodies correlates with problems in blood pressure regulation. The findings provide a new opening to potentially understanding the causes of LC, and so provide direction for the development of new treatments.},
}

@article {pmid40690153,
year = {2025},
author = {Abbasi, A and Sharma, R and Hansen, N and Pirrotte, P and Stringer, WW},
title = {Possible long COVID biomarker: identification of SARC-CoV-2 related protein(s) in Serum Extracellular Vesicles.},
journal = {Infection},
volume = {},
number = {},
pages = {},
pmid = {40690153},
issn = {1439-0973},
}

@article {pmid40687082,
year = {2025},
author = {Motokawa, Y and Sugihara, J and Tateishi, T and Hosoya, T and Yasuda, S and Miyazaki, Y and Takahashi, H and Shiwaku, H},
title = {Long COVID is associated with female sex; Anti-NCAM1 autoantibodies are absent in patients with long COVID.},
journal = {IBRO neuroscience reports},
volume = {19},
number = {},
pages = {252-256},
pmid = {40687082},
issn = {2667-2421},
abstract = {BACKGROUND: Long COVID is a condition that may arise following SARS-CoV-2 infection and is associated with a range of systemic complications. Autoantibodies are implicated in the pathogenesis of long COVID. However, the details of the pathogenic mechanisms undergone by these autoantibodies remain unclear. Neural cell adhesion molecule 1 (NCAM1) is the human protein with the highest sequence homology to the SARS-CoV-2 proteins. Previous in silico studies indicate that SARS-CoV-2 infection may induce the production of anti-NCAM1 autoantibodies. Thus, this study investigated the presence of anti-NCAM1 autoantibodies in individuals affected by COVID-19, including those with long COVID.

METHODS: Serum samples were obtained from 173 individuals 3 months after SARS-CoV-2 infection. Among them, 63 were diagnosed with long COVID. A cell-based assay was used to assess all 173 serum samples for the presence of anti-NCAM1 autoantibodies. We also analyzed the clinical profiles of patients with and without long COVID to identify potential risk factors associated with long COVID.

RESULTS: Anti-NCAM1 autoantibodies were not detected in any serum sample. The proportion of female patients in the long COVID group was significantly higher than that in the non-long COVID group.

CONCLUSION: The results indicate that the production of anti-NCAM1 autoantibodies following COVID-19 is unlikely. Female sex is associated with higher risk of long COVID.},
}

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

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

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

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

REGISTRATION: PROSPERO (CRD42023440141).},
}

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

@article {pmid40042337,
year = {2025},
author = {Ford, ND and Baca, S and Dalton, AF and Koumans, EH and Raykin, J and Patel, PR and Saydah, S},
title = {Use and Characteristics of Clinical Coding for Post-COVID Conditions in a Retrospective US Cohort.},
journal = {Journal of public health management and practice : JPHMP},
volume = {31},
number = {5},
pages = {E292-E302},
pmid = {40042337},
issn = {1550-5022},
mesh = {Humans ; Retrospective Studies ; *COVID-19/complications/epidemiology ; United States/epidemiology ; Female ; Male ; *Clinical Coding/statistics & numerical data/methods/standards ; Middle Aged ; Adult ; Aged ; International Classification of Diseases ; Child ; SARS-CoV-2 ; Cohort Studies ; },
abstract = {CONTEXT: Little is known about when and how the ICD-10-CM diagnosis code for Post-COVID Conditions (PCC; U09.9) is being used to document PCC.

OBJECTIVES: To examine the use and characteristics of clinical coding for PCC.

DESIGN: A retrospective cohort.

SETTING: Transaction-level medical encounters, laboratory testing results, pharmacy claims, and medical claims for inpatient and outpatient care from the HealthVerity database.

PARTICIPANTS: 382 400 US adults and children with private health insurance, Medicare, and Medicaid who had U09.9 code documented during October 1, 2021-June 30, 2023.

OUTCOME MEASURES: Count of first use of the U09.9 code, (a) overall, over time, and proportion by provider type; (b) prevalence of PCC-associated incident conditions co-documented with U09.9; (c) number of documented SARS-CoV-2 infections preceding U09.9; (d) timing between infection and U09.9; (e) encounters during the 6 months following first use of U09.9.

RESULTS: Overall, 0.6% of 65 556 068 patients had a PCC diagnosis code (64.6% female; 6 in 10 had ≥1 preexisting conditions). The highest count of new U09.9 codes occurred during Quarter 1 and Quarter 3 of 2022 and was documented by a variety of provider specialties. The most prevalent co-documented PCC-associated incident conditions were respiratory (13.4%) and malaise and fatigue (7.8%). Only 62% of patients had SARS-CoV-2 infection documented preceding U09.9; median time to PCC documentation was 17.0 days (interquartile range [IQR] = 5.0, 61.0). Patients with ≥1 encounters during which PCC was documented in the 6 months following their index encounter (n = 109 794) had, on average, 25.5 additional encounters (median = 14 [IQR = 7, 29]).

CONCLUSIONS: Our study describes the sociodemographic characteristics, complex clinical manifestations, and high healthcare use of patients following a PCC diagnosis. These findings may inform efforts to identify and treat PCC, inform healthcare planning, and support efforts to educate clinicians about the definition of PCC and accurate application of the code.},
}

Humans
Retrospective Studies
*COVID-19/complications/epidemiology
United States/epidemiology
Female
Male
*Clinical Coding/statistics & numerical data/methods/standards
Middle Aged
Adult
Aged
International Classification of Diseases
Child
SARS-CoV-2
Cohort Studies

@article {pmid40684788,
year = {2025},
author = {Kirby, T},
title = {Joan B Soriano-expert on asthma, COPD, and long COVID.},
journal = {The Lancet. Respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2213-2600(25)00253-X},
pmid = {40684788},
issn = {2213-2619},
}

@article {pmid40684361,
year = {2025},
author = {Baldassarre, G and Zuccarelli, L and Favaretto, T and Ursella, C and Palomba, A and Salvador, PCDN and Sozio, E and Crisafulli, E and Imazio, M and Tascini, C and Grassi, B},
title = {Persistence of fatigue in the absence of pathophysiological mechanisms in some patients more than 2 years after the original SARS-CoV-2 infection.},
journal = {Experimental physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/EP092850},
pmid = {40684361},
issn = {1469-445X},
abstract = {Following an acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a substantial percentage of patients report the persistence of debilitating symptoms, often grouped in a syndrome termed 'long COVID'. We sought to identify potential pathophysiological mechanisms responsible for the persistence, in some long COVID patients, of symptoms related to fatigue/exercise intolerance (excessive or early fatigue, excessive or early dyspnoea, muscle weakness, and myalgias) more than 2 years after the original infection. Twelve patients who reported persistent symptoms (Long COVID group; 57 ± 6 years, mean ± SD), and 14 patients without the symptoms (Control group; 57 ± 8 years) were evaluated. An extensive series of measurements were performed to identify pathophysiological mechanisms potentially responsible for the symptoms. In long COVID patients, all items evaluating quality of life (SF-36 questionnaire) had lower scores (P < 0.01) compared to control. The habitual level of physical activity, muscle size and strength, maximal aerobic power and the ventilatory thresholds, peak cardiac function, the mechanical efficiency of cycling, pulmonary V ̇ O 2 ${\dot V_{{{\mathrm{O}}
_2}}
}$
kinetics, microvascular/endothelial function (hyperemic response in the common femoral artery during passive leg movements), skeletal muscle oxidative metabolism (peak fractional O2 extraction and muscle V ̇ O 2 ${\dot V_{{{\mathrm{O}}
_2}}
}$
recovery kinetics by the repeated occlusions test, by near-infrared spectroscopy) were not different in the two groups. Evidence of ventilatory inefficiency was described in a subgroup of long COVID patients. More than 2 years after the original SARS-CoV-2 infection, a discrepancy was observed between the persistence of debilitating symptoms of fatigue/exercise intolerance and the absence of several investigated pathophysiological mechanisms. The discrepancy may be due to factors that remain to be elucidated.},
}

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

@article {pmid40613609,
year = {2025},
author = {Cooper, J and Haroon, S and Crowe, F and Nirantharakumar, K and Jackson, T and Fitzsimmons, L and Hathaway, E and Flanagan, S and Marshall, T and Jackson, LJ and Gunathilaka, N and D'Elia, A and Morris, SG and Greenfield, S},
title = {Perspectives of Health Care Professionals on the Use of AI to Support Clinical Decision-Making in the Management of Multiple Long-Term Conditions: Interview Study.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e71980},
pmid = {40613609},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; *Health Personnel/psychology ; *Clinical Decision-Making ; *Attitude of Health Personnel ; Interviews as Topic ; *Multiple Chronic Conditions/therapy ; Male ; Female ; Primary Health Care ; },
abstract = {BACKGROUND: Managing multiple long-term conditions (MLTC) is complex. Clinical management guidelines are typically focused on individual conditions and lack a robust evidence base for patients with MLTC. MLTC management is largely delivered in primary care, where health care professionals (HCPs) have identified the need for more holistic yet efficient models of care that can address patients' medical, pharmacological, social, and mental health needs. Artificial intelligence (AI) has proven effective in tackling complex, data-driven challenges in various fields, presenting significant opportunities for MLTC care. However, its role in managing patients with multifaceted psychosocial needs remains underexplored. The implementation of AI tools in this context introduces opportunities for innovation and challenges related to clinical appropriateness, trust, and ethical considerations. Understanding HCPs' experiences of MLTC management and the factors influencing their attitudes toward using AI in complex clinical decision-making is crucial for successful implementation.

OBJECTIVE: We aimed to explore the perspectives of primary care HCPs on managing MLTC and their attitudes toward using AI tools to support clinical decision-making in MLTC care.

METHODS: In total, 20 HCPs, including general practitioners, geriatricians, nurses, and pharmacists, were interviewed. A patient case study was used to explore how an AI tool might alter the way in which participants approach clinical decision-making with a patient with MLTC. We derived concepts inductively from the interview transcripts and structured them according to the 5 categories of the model by Buck exploring determinants of attitudes toward AI. These included the concerns and expectations that contributed to the minimum requirements for HCPs to consider using an AI decision-making tool, as well as the individual characteristics and environmental influences determining their attitudes.

RESULTS: HCPs' perspectives on managing MLTC were grouped into three main themes: (1) balancing multiple competing factors, including accounting for patients' social circumstances; (2) managing polypharmacy; and (3) working beyond single-condition guidelines. HCPs typically expected that AI tools would improve the safety and quality of clinical decision-making. However, they expressed concerns about the impact on the therapeutic clinician-patient relationship that is fundamental to the care of patients with MLTC. The key prerequisites for clinicians adopting AI tools in this context included improving public and patient trust in AI, saving time and integrating with existing systems, and ensuring that the rationale behind a recommendation is apparent to enable a final decision made by an experienced human clinician.

CONCLUSIONS: This is the first study to examine the attitudes of HCPs toward using AI decision-making tools in the context of managing MLTC. HCPs were optimistic about AI's potential to improve decision-making safety and quality but emphasized that the human touch remains essential for patients with complex needs. We identified critical requirements for AI adoption, including addressing patients' perceptions, time efficiency, and the preservation of clinician and patient autonomy.

RR2-10.1136/bmjopen-2023-077156.},
}

Humans
*Artificial Intelligence
*Health Personnel/psychology
*Clinical Decision-Making
*Attitude of Health Personnel
Interviews as Topic
*Multiple Chronic Conditions/therapy
Male
Female
Primary Health Care

@article {pmid40682988,
year = {2025},
author = {Carvalho, LLM and Goulart, CDL and Pierazzo, GDD and Cordeiro-Costa, EL and Borghi-Silva, A and Garcia-Araújo, AS},
title = {Associations between lung and endothelial function in long COVID: Two years after acute infection.},
journal = {Heart & lung : the journal of critical care},
volume = {74},
number = {},
pages = {168-173},
doi = {10.1016/j.hrtlng.2025.07.011},
pmid = {40682988},
issn = {1527-3288},
abstract = {BACKGROUND: endothelial cells may be a primary source for the initiation and spread of Acute Respiratory Distress Syndrome (ARDS) caused by SARS-CoV-2, resulting in severe endothelial injury and widespread thrombosis.

OBJECTIVE: The objective of this study was to evaluate the influence of lung function on the vascular response of patients with long COVID.

METHODS: This is an observational and cross-sectional study. Only one visit was performed, during which the evaluation form was completed and the post-COVID-19 Functional Status Scale (PCFS) was applied. In addition, participants underwent the assessment of flow-mediated vasodilation in the brachial artery and the assessment of pulmonary function.

RESULTS: A total of 32 participants were included, of which 19 (59 %) were women. The mean age was 55.8 ± 8.6 years, with a mean weight of 88.96 ± 21.66 kg. The participants had an average time of 32.25 months since the acute phase. The patients had an average of FEV₁/FVC 81.15±14.7 (%) and KCO 93.72±7.95 (%). FMD had an average of -0.21±11.24 (%), indicating still impaired endothelial function. We found correlation between basal diameter (-0.21 [-4.26 to 3.84]) vs lung function variables, especially with the variable KCO (%) (p < 0.001; r = 0.560). When we perform simple linear regression KCO (%) indicates that this variable alone influences 29 % of the response to the basal diameter of the participants.

CONCLUSION: Two years after recovery from COVID-19 infection, the patients present changes in endothelial function, which have important implications for individuals when it comes to cardiovascular health.},
}

@article {pmid40680857,
year = {2025},
author = {Melkumyan, K and Simonyan, S and Shingala, D and Torossian, H and Mkrtumyan, K and Tulbenjyan, M and Hovhannisyan, Y and Yenkoyan, K},
title = {3-Year Assessment of Cognitive and Olfactory Disturbances Among COVID-19 Convalescent Patients Grouped by Olfactory Hallucination Status in Armenia: A Qualitative and Quantitative Study.},
journal = {Clinical medicine (London, England)},
volume = {},
number = {},
pages = {100489},
doi = {10.1016/j.clinme.2025.100489},
pmid = {40680857},
issn = {1473-4893},
abstract = {BACKGROUND: Smell disturbances, memory, and mood changes are frequently reported as long-COVID symptoms that can be debilitating and long-lasting, having a detrimental impact on a patient's quality of life and possibly contributing to depression and a decline in cognitive abilities.

OBJECTIVE: This study aims to investigate long-term post-COVID cognitive and olfactory disturbances among the COVID-19 convalescent adult Armenian population aged between 18 and 65 years. The assessment extends to the differentiation of various olfactory distortions and association between various olfactory and cognitive variables grouped by participants' olfactory hallucination status.

DESIGN: Explanatory sequential mixed-methods design was employed. Through three follow-up visits, the quantitative phase evaluated olfactory and cognitive abnormalities following COVID-19, comparing those with and without olfactory hallucinations. Through in-depth interviews, the qualitative phase investigated how participants perceived these symptoms and their impact on their quality of life.

PARTICIPANTS: The quantitative study participants were those who self-reported subjective disturbances in the olfactory perception 14 days following a COVID-19 diagnosis, as confirmed by a positive PCR test at the time of diagnosis. The qualitative study participants were those who self-reported persistent olfactory disturbances post-visit 3.

RESULTS: The study found that olfactory hallucinations lead to more pronounced depression as compared to non-hallucinogenic types of olfactory disturbances. It was determined that a significant predictor of parosmia is persistent anosmia up to four months following COVID-19 infection.

CONCLUSION: The long-term olfactory disturbances post-COVID-19 infection have a better prognosis among participants without olfactory hallucination as compared to participants with olfactory hallucination.},
}

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

@article {pmid40680016,
year = {2025},
author = {Dorney, J and Ebna Mannan, I and Malicki, C and Wisk, LE and Elmore, J and O'Laughlin, KN and Morse, D and Gatling, K and Gottlieb, M and Santangelo, M and L'Hommedieu, M and Gentile, NL and Saydah, S and Hill, MJ and Huebinger, R and Martin, KR and Idris, AH and Kean, E and Schaeffer, K and Rodriguez, RM and Weinstein, RA and Spatz, ES and , },
title = {Impact of SARS-CoV-2 on healthcare and essential workers: A longitudinal study of PROMIS-29 outcomes.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0324755},
pmid = {40680016},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/psychology/virology ; *Health Personnel/psychology/statistics & numerical data ; Male ; Female ; Adult ; Longitudinal Studies ; Middle Aged ; SARS-CoV-2/isolation & purification ; Employment ; Patient Reported Outcome Measures ; Pandemics ; United States/epidemiology ; Frontline Workers ; },
abstract = {IMPORTANCE: The mandatory service of essential workers during the COVID-19 pandemic was associated with high job stress, increased SARS-CoV-2 exposure, and limited time for recovery following infection. Understanding outcomes for frontline workers can inform planning for future pandemics.

OBJECTIVE: To compare patient-reported outcomes by employment type and SARS-CoV-2 status.

DESIGN: Data from the INSPIRE registry, which enrolled COVID-positive and COVID-negative adults between 12/7/2020-8/29/2022 was analyzed. Patient-reported outcomes were collected quarterly over 18 months.

SETTING: Participants were recruited across eight US sites.

PARTICIPANTS: Employed INSPIRE participants who completed a short (3-month) and long-term (12-18 month) survey.

EXPOSURE: SARS-CoV-2 index status and employment type (essential healthcare worker [HCW], essential non-HCW, and non-essential worker ["general worker"]).

MAIN OUTCOMES AND MEASURES: PROMIS-29 (mental and physical health summary) and PROMIS Cognitive SF-CF 8a (cognitive function) scores were assessed at baseline, short-term (3-months), and long-term (12-18 months) timepoints using GEE modeling.

RESULTS: Of the 1,463 participants: 53.5% were essential workers (51.4% HCWs, 48.6% non-HCWs) and 46.5% were general workers. Most associations between outcomes and employment type became non-significant after adjusting for sociodemographics, comorbidities, COVID-19 vaccination, and SARS-CoV-2 variant period. However, among COVID-negative participants, essential HCWs had higher cognitive scores at baseline (β: 3.91, 95% CI [1.32, 6.50]), short term: (β: 3.49, 95% CI: [0.80, 6.18]) and long-term: (β: 3.72, 95% CI: [0.98, 6.46]) compared to general workers. Among COVID-positive participants, essential non-HCWs had significantly worse long-term physical health summary scores (β:-1.22, 95% CI: [-2.35, -0.09]) compared to general workers.

CONCLUSIONS AND RELEVANCE: Differences in outcomes by worker status were largely explained by baseline characteristics. However, compared to general workers, essential HCW status had higher cognitive function in the absence of SARS-CoV-2 infection at all timepoints, while essential non-HCWs were most vulnerable to poor recovery in long-term physical health following SARS-CoV-2 infection. Preparation efforts for future pandemics may consider enhanced protection and post-infection resources for frontline workers.},
}

Humans
*COVID-19/epidemiology/psychology/virology
*Health Personnel/psychology/statistics & numerical data
Male
Female
Adult
Longitudinal Studies
Middle Aged
SARS-CoV-2/isolation & purification
Employment
Patient Reported Outcome Measures
Pandemics
United States/epidemiology
Frontline Workers

@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 {pmid40676931,
year = {2025},
author = {Abdul-Azees, PA and Marinkovic, M and Singh, BB and Dean, DD and Chen, XD and Goldberg, MP and Restrepo, MI and Loomer, PM and Yeh, CK},
title = {The Impact of Aging Oral Health on Long COVID-19.},
journal = {Journal of dental research},
volume = {},
number = {},
pages = {220345251349805},
doi = {10.1177/00220345251349805},
pmid = {40676931},
issn = {1544-0591},
abstract = {At least 10% of individuals infected with SARS-CoV-2 develop a variety of multisystem symptoms lasting more than 12 wk known as postacute sequelae of COVID-19 (PASC) or "long COVID." While the precise pathogenesis of PASC remains unclear, immune dysregulation is widely recognized as a key factor. Moreover, PASC disproportionately affects older individuals who are prone to age-related immune system decline, which further exacerbates the risk and severity of PASC. The oral cavity, a primary site for initial SARS-CoV-2 infection, may contribute to the development and persistence of PASC. Emerging evidence suggests that changes in age-related oral health, such as periodontitis, salivary gland (SG) dysfunction, and gustatory and olfactory impairments, may create an environment conducive to forming an oral reservoir of intact virus or viral antigens, which may contribute to the chronicity of PASC. Alternatively, the pathogenesis of PASC may increase the risk of a wide range of oral health issues, such as dental diseases, dry mouth, and sensory dysfunction (e.g., taste and smell) that are frequently reported by patients with PASC. This review highlights how aging facilitates oral SARS-CoV-2 infection, co-infection with other viruses may drive PASC in aging patients, aging and PASC dysregulate the oral microbiome, SARS-CoV-2 infection promotes molecular mechanisms involved in oral tissue aging, aging oral health affects susceptibility to developing PASC, and inflammation associated with PASC exacerbates dysregulation of metabolic/enzymatic pathways of aging oral mucosa and diseases of the periodontal apparatus, SGs, and taste. It underscores the urgent need to comprehensively address the interplay between aging oral health and PASC, which will help mitigate long-term complications and improve overall health outcomes for affected individuals.},
}

@article {pmid40672484,
year = {2025},
author = {Yadaw, AS and Sahner, DK and Sid, E and Chew, EY and Pichard, D and Mathé, EA},
title = {Impact of Preexisting Rare Diseases on COVID-19 Severity, Reinfection, and Long COVID, and the Modifying Effects of Vaccination and Antiviral Therapy: A Retrospective Study from the N3C Data Enclave.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.07.09.25331138},
pmid = {40672484},
abstract = {BACKGROUND: Over 10,000 rare diseases (RDs) affect more than 300 million people globally, yet their influence on COVID-19 severity, reinfection risk, and long COVID remains poorly understood. This study evaluates the impact of RDs on these outcomes and examines the effectiveness of vaccination and antiviral treatments among individuals with and without RDs.

METHODS: We conducted a retrospective cohort study using harmonized electronic health records (EHRs) from the National COVID Cohort Collaborative (N3C), encompassing 21,704,702 individuals, including 4,825,605 with confirmed SARS-CoV-2 infection between Jan 1, 2020, and Jan 4, 2024. RDs were defined using 12,003 conditions curated from GARD and Orphanet, mapped to OMOP concepts, and classified into 18 RD classes based on medical specialty involvement. Primary outcomes included: (1) COVID-19 severity (hospitalization and life-threatening disease), (2) long COVID, and (3) SARS-CoV-2 reinfection. We applied multivariable logistic regression with inverse probability of treatment weighting and reported adjusted odds ratios with 95% confidence intervals and associated p-values. Models were controlled for demographics, comorbidities, and exposure to vaccination and antiviral treatments.

FINDINGS: Of 21,704,702 individuals, we identify 4,825,605 COVID-19 positive individuals, 6.36% had RDs, with markedly higher rates of rare disease (RD) patients that have life-threatening illness (16% vs. 6.1% without life-threatening illness) and that are hospitalized (13% vs. 6.0% without hospitalization). Otorhinolaryngologic diseases showed the highest risk of life-threatening outcomes (OR 4.51; 95% CI 3.81-5.33), followed by developmental defect during embryogenesis (OR 1.84; 95% CI 1.72-1.98) and cardiac conditions (OR 1.79; 95% CI 1.51-2.11). Hospitalization risk was highest for otorhinolaryngologic (OR 2.90; 95% CI 2.61-3.23), developmental defect during embryogenesis (OR 2.06; 95% CI 1.97-2.16), and hematologic and endocrine diseases (OR 1.81; 95% CI 1.75-1.87 and OR 1.81; 95% CI 1.64-1.99, respectively).In patients with RDs, vaccination alone or antiviral treatment alone was associated with reduced odds of life-threatening COVID-19 disease compared to non-vaccinated individuals (OR 0.71; 95% CI 0.66-0.77 and OR 0.33; 95% CI 0.26-0.42, respectively). The combination of both vaccination and antiviral treatment showed the greatest reduction in odds ratio (OR 0.24; 95% CI 0.20-0.27). Similar results were observed in patients without RDs. In contrast, vaccination or antiviral therapy alone, compared to no intervention, did not significantly reduce long COVID risk in RD patients, although these interventions alone did result in a lower odds ratio in patients without RD. However, their combination was protective in both groups. Vaccination alone, compared to no vaccination, also reduced the risk of reinfection across RD and non-RD populations.

INTERPRETATION: RD patients face elevated risks of severe COVID-19 outcomes. While vaccination and antivirals significantly reduce the acute severity of illness, their impact on long COVID appears limited in this population. Notably, vaccination was protective against COVID-19 reinfection in both RD and non-RD populations. These findings highlight the need for targeted strategies to protect RD patients beyond current interventions, particularly in preventing long-term complications.

FUNDING: This work was supported in part by the intramural and extramural programs at NCATS (ZIA ZICTR000410).},
}

@article {pmid40671933,
year = {2025},
author = {Zeballos, RS and da Silva Helbingen, MF and Melo, PMP and Alves, FEC and Salvino, CR and Seródio, EP and de Carvalho, ERM},
title = {Post spike syndrome (PSS): Simple solution leading to resolving results, five cases report.},
journal = {IDCases},
volume = {41},
number = {},
pages = {e02278},
pmid = {40671933},
issn = {2214-2509},
abstract = {UNLABELLED: Post-Spike Syndrome (PSS) is an emerging condition associated with the Spike protein, originating from both SARS-CoV-2 infection and mRNA-based therapies. This case series explores the significant clinical impact of PSS, characterized By gut dysbiosis, systemic inflammation, and immune activation, leading to multisystem manifestations such as fatigue, brain fog, neuropathies, and reactivation of pre-existing diseases. A simple therapeutic approach was applied to five patients, resulting in notable symptom improvement.

METHODS: This case series includes five patients diagnosed with interstitial granulomatous dermatitis, polymyalgia rheumatica, peripheral polyneuropathy, drug-refractory epilepsy, and trigeminal neuralgia. A common pathophysiological mechanism-vasculitis triggered by both SARS-CoV-2 and mRNA-based therapies-was hypothesised. The patients exhibited a satisfactory response to the proposed therapeutic strategy. This is an observational and descriptive study, with data collected retrospectively from medical records at a private clinic in São Paulo, Brazil.

CONCLUSION: It is crucial to raise awareness within the medical community About SPIKEOPATHY, particularly in cases of classic pathologies that do not respond to conventional treatments. We believe PSS is currently underestimated. A broad intervention including a focus on restoring the microbiome, in particular Bifidobacterium associated with ivermectin and nattokinase was used as a therapeutic strategy. In other studies, Bifidobacterium has already been shown to significantly reduce harmful bactéria in post-COVID patients. Further studies are needed to confirm these findings and expand our understanding of PSS management.},
}

@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 {pmid40670209,
year = {2025},
author = {Zhou, YT and Chang, TH and Lin, CW and Shang, CY and Chen, SH and Shih, AT and Chen, FL and Gau, SS and Chang, LY},
title = {The impact of COVID-19 on psychophysiology and quality of life among children during omicron surge in Taiwan.},
journal = {Pediatrics and neonatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pedneo.2025.04.005},
pmid = {40670209},
issn = {2212-1692},
abstract = {BACKGROUND: Taiwan experienced an outbreak of the COVID-19 omicron variant in March 2022. We investigated the impact of COVID-19 on the psychophysiology and quality of life of children.

METHODS: We enrolled children under 18 from June to November 2023, dividing them into three groups based on their COVID-19 history: simple COVID, long COVID, and non-COVID. We collected demographic data and symptoms and conducted various surveys including the Modified Medical Research Council dyspnea scale, Pediatric Quality of Life Inventory Multidimensional Fatigue Scale, Patient Health Questionnaire-9, International Positive and Negative Affect Schedule Short-Form, Family APGAR, social and school behaviors, and family cohesion.

RESULTS: Of the 797 subjects, 573 (71.9 %) were confirmed cases, and 224 (28.1 %) were not infected. Fourteen percent (84/573) reported symptoms lasting over three months and were classified into the long COVID group. The long COVID group had significantly more physical and psychological symptoms than the non-COVID group (all p < 0.05). Compared to the simple COVID and non-COVID groups, the long COVID group showed significantly more fatigue, higher severe mMRC grades, greater depression tendencies, higher negative affect scores, and lower well-being (all p < 0.001). Additionally, depressive children in the COVID group experienced more stress about returning to school (p = 0.01), more family dysfunction (p = 0.01), less family support (p = 0.008), and fewer problem-solving abilities in their families (p = 0.008).

CONCLUSION: The long COVID group had more severe physical and psychological symptoms, family dysfunction, and school-related stress, indicating a need for further assistance.},
}

@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 {pmid40668129,
year = {2025},
author = {Wambui, D and Fiellin, M and Majka, C and Espineli, C and Flattery, J and Vergara, X},
title = {Prevalence and Risk Factors for Long COVID among California Workers Captured by a Doctor's First Report-Based Surveillance System.},
journal = {Journal of occupational and environmental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1097/JOM.0000000000003497},
pmid = {40668129},
issn = {1536-5948},
abstract = {OBJECTIVE: To understand prevalence and risk factors for long COVID among California workers.

METHODS: Using a cross-sectional study design, we analyzed 4,496 Doctor's First Reports of Occupational Injury or Illness (DFRs) used for tracking work-related COVID-19 exposure or illnesses. Logistic regression was used to assess the risk factors.

RESULTS: With a prevalence of 11%, long COVID cases were slightly higher among male workers, workers aged between 45 - 54 years, and those in essential industries. Over 30 days of lost work was 13 times more prevalent among long COVID cases compared to acute cases. Age, presenting symptoms, and working in mixed essential industries increased long COVID risk.

CONCLUSION: These findings highlight long COVID burden on workers' health and productivity. Proactive measures are crucial to safeguard workers' health.},
}

@article {pmid40667921,
year = {2025},
author = {Barbosa, DAM and Ferraz-Pereira, KN and Conceição, EHD and Santos, REA and Lins, ID and Maior, CS and Araujo, AV and DO Vale Gomes, AL},
title = {Olfaction and taste disorders in Covid-19: prevalence, long-term persistence and impact on quality of life and eating habits of health professionals.},
journal = {Anais da Academia Brasileira de Ciencias},
volume = {97},
number = {3},
pages = {e20240392},
doi = {10.1590/0001-3765202520240392},
pmid = {40667921},
issn = {1678-2690},
mesh = {Humans ; *COVID-19/complications/epidemiology ; *Taste Disorders/epidemiology/etiology/virology ; *Olfaction Disorders/epidemiology/etiology/virology ; Female ; Male ; Prevalence ; Adult ; Middle Aged ; *Health Personnel/statistics & numerical data ; *Quality of Life ; *Feeding Behavior ; SARS-CoV-2 ; Surveys and Questionnaires ; Brazil/epidemiology ; },
abstract = {The objective was to assess the prevalence and long-term persistence of olfactory and taste disorders among health professionals in the context of COVID-19. The study was carried out with 53 professionals, who were divided into 3 groups: (1) IgA and/or IgG positive for SARS-CoV-2 with loss of smell and/or taste (n=37); (2) IgA and/or IgG positive for SARS-CoV-2 without loss of smell and/or taste (n=7); and (3) IgA and IgG negative for SARS-CoV-2 (n=9). The collection of information was made using questionnaires by telephone contact. Symptoms of malaise and loss of smell and/or taste revealed an association with COVID-19 test results. Of the 53 participants, 39 reported impaired smell and taste, 37 with a positive diagnosis, and 2 with a negative diagnosis. Of the 53 professionals, 31 had Long COVID; the longest-lasting symptoms were loss of smell and taste. The study showed that there is a high prevalence of olfactory and/or taste alterations, both in the short and the long term, in individuals who tested positive for COVID-19.},
}

Humans
*COVID-19/complications/epidemiology
*Taste Disorders/epidemiology/etiology/virology
*Olfaction Disorders/epidemiology/etiology/virology
Female
Male
Prevalence
Adult
Middle Aged
*Health Personnel/statistics & numerical data
*Quality of Life
*Feeding Behavior
SARS-CoV-2
Surveys and Questionnaires
Brazil/epidemiology

@article {pmid40667844,
year = {2025},
author = {Hung, CT and Wang, LM and Lee, YJ and Suk, CW and Kok, CY},
title = {Association of Nirmatrelvir/Ritonavir and the Risk of Long COVID Among US Adults: A Multicenter Retrospective Cohort Study.},
journal = {Journal of medical virology},
volume = {97},
number = {7},
pages = {e70494},
doi = {10.1002/jmv.70494},
pmid = {40667844},
issn = {1096-9071},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; Retrospective Studies ; Male ; *Ritonavir/therapeutic use ; Female ; Middle Aged ; *COVID-19 Drug Treatment ; Adult ; *Antiviral Agents/therapeutic use ; *COVID-19/epidemiology ; Aged ; United States/epidemiology ; SARS-CoV-2/drug effects ; },
abstract = {Nirmatrelvir/ritonavir (NMV-r) is an oral antiviral agent authorized for treating acute COVID-19, but its effectiveness in reducing long COVID risk remains uncertain. This multicenter retrospective cohort study aimed to evaluate the association between NMV-r and the risk of long COVID. Electronic health record data from the TriNetX US Collaborative Network were used. Adults aged ≥ 18 years with a positive COVID-19 test between January 1, 2022 and June 30, 2024 were included. NMV-r users were those who received NMV-r within 5 days of testing positive, while those who did not receive NMV-r within this period were the nonusers. The outcome was time to the first diagnosis of incident post-COVID conditions, including general, pulmonary, cardiac, thromboembolic, neurologic, mental, musculoskeletal, gastrointestinal, and kidney symptoms. Propensity score matching was performed to balance baseline characteristics and Cox proportional hazards models were used to estimate the risk of long COVID between NMV-r users and nonusers. Both groups included 218 825 patients after matching. Overall, the risk of long COVID was similar between NMV-r users and nonusers (HR, 0.99; 95% CI, 0.98-1.01). Symptom-specific analyses revealed mixed effects, with NMV-r use associated with an increased risk of cough and sleeping disorders but a decreased risk for other long COVID symptoms. Sensitivity analyses showed consistent results with the main analysis. In conclusion, NMV-r use was not associated with a reduced risk of long COVID. Future research is needed to explore its heterogeneous effects on post-COVID conditions.},
}

Humans
Retrospective Studies
Male
*Ritonavir/therapeutic use
Female
Middle Aged
*COVID-19 Drug Treatment
Adult
*Antiviral Agents/therapeutic use
*COVID-19/epidemiology
Aged
United States/epidemiology
SARS-CoV-2/drug effects

@article {pmid40667466,
year = {2025},
author = {Fradkin, T and Schmidt-Kastner, R},
title = {A data-mining analysis of host solute carrier family proteins in SARS-CoV-2 infection with reference to brain endothelial cells and the blood-brain barrier in COVID-19.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1563040},
pmid = {40667466},
issn = {1664-2295},
abstract = {BACKGROUND: The brain vasculature is a key player in neurological manifestations of COVID-19. Infection of brain endothelial cells with SARS-CoV-2 along with circulating cytokines may cause dysfunction of the blood-brain barrier (BBB). Solute carrier transporters (SLCs) in brain endothelial cells regulate substrate transport across the BBB. Here, it was hypothesized that transport functions of SLCs will be impaired by interactions with viral proteins, and subsequently, data-mining studies were performed.

METHODS: Virus-host protein-protein interaction data for SARS-CoV-2 infection were retrieved from the BioGRID database, filtered for SLCs, and then annotated for relevant expression in brain endothelial cells using a mouse brain transcriptomics database. Host SLCs expressed in brain endothelial cells were further explored using publicly available databases and information in the literature. Functional Annotation Clustering was performed using DAVID, and Enrichr served for pathway analysis. Substrates were retrieved from NCBI Gene. Links to monogenic disorders were retrieved from Online Mendelian Inheritance in Man™ and screened for disorders of the nervous system. Interactome data for viral proteins of SARS-CoV-2 were retrieved from BioGRID. Reports for host SLCs in viral receptor functions, viral entry mechanisms, and other major roles in the viral cycle were explored in databases (VThunter) and literature. ATP-binding cassette transporters (ABCs) were studied in parallel.

RESULTS: N = 80 host SLCs showed relevant expression in brain endothelial cells whereby amino acid transporter stood out. N = 24/80 host SLCs were linked to monogenic disorders of the nervous system. N = 9/29 SARS-CoV-2 viral proteins had strong links to SLCs and key functions in viral infection (e.g., interferon response). SLCs serving as viral receptors and with closely associated functions were significantly enriched among all known listed viral receptors (chi-square test, p = 0.001). Literature searches for host SLCs revealed involvement of a subset of SLCs in infection mechanisms for SARS-CoV-2 and more broadly for other viruses. N = 17 host ABCs were found in brain endothelial cells where they may serve as efflux transporters.

DISCUSSION: This hypothesis-generating work proposes a set of N = 80 host SLCs expressed in endothelial cells as contributors to BBB impairment after SARS-CoV-2 infection. Theoretically, persistent dysfunction of SLCs at the BBB, in particular insufficient transport of amino acids, could be one of many reasons for cognitive changes in long-COVID. Functions of SLCs in viral entry and associated roles deserve close attention.},
}

@article {pmid40663544,
year = {2025},
author = {, },
title = {Correction: Association between long COVID and nonsteroidal anti-inflammatory drug use by patients with acute-phase COVID-19: A nationwide Korea National Health Insurance Service cohort study.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0328398},
doi = {10.1371/journal.pone.0328398},
pmid = {40663544},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0312530.].},
}

@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 {pmid40661336,
year = {2025},
author = {Rasouli, R and Hartl, B and Konecky, SD},
title = {Low-intensity ultrasound lysis of amyloid microclots in a lab-on-chip model.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {13},
number = {},
pages = {1604447},
pmid = {40661336},
issn = {2296-4185},
abstract = {Amyloid fibrin(ogen) microclots are misfolded protein aggregates with β-sheet structures that have been associated with Long COVID and numerous thrombo-inflammatory diseases. These microclots persist in circulation and obstruct microvasculature, impair oxygen transport and promote chronic inflammation. Conventional thrombolytic therapies such as recombinant tissue plasminogen activator (rtPA) show limited efficacy against these microclots due to their structure and composition. In this study, we assess the impact of low intensity focused ultrasound (LIFU) stimulation on amyloid microclot fragmentation, the role of cavitation in this process and investigate whether microbubble-assisted ultrasound can enhance their lysis. Amyloid microclot models were generated using freeze-thaw cycles followed by incubation. Microclots were exposed to ultrasound waves at 150, 300, 500 kHz, and 1 MHz under four conditions: ultrasound alone (US), ultrasound with microbubbles (MB + US), ultrasound with rtPA (rtPA + US), and ultrasound with both microbubbles and rtPA (MB + rtPA + US). Low-frequency ultrasound at 150 kHz resulted in a significant clot lysis with up to three-fold reduction in both clot size and the number of large clots. The addition of microbubbles enhanced clot lysis at 150, 300, and 500 kHz. These findings suggest that ultrasound, particularly at 150 kHz is a promising method for amyloid microclot lysis. The combination of ultrasound with microbubbles and rtPA further improved clot fragmentation, rendering it a potential therapeutic tool for conditions like Long COVID.},
}

@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 = {},
number = {},
pages = {},
doi = {10.1080/17460441.2025.2534056},
pmid = {40660830},
issn = {1746-045X},
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.},
}

@article {pmid40660536,
year = {2025},
author = {Takezawa, H},
title = {Successful treatment of long-COVID postural tachycardia syndrome with epipharyngeal abrasive therapy in an adolescent patient: A case report.},
journal = {Medicine},
volume = {104},
number = {28},
pages = {e43333},
pmid = {40660536},
issn = {1536-5964},
mesh = {Adolescent ; Humans ; *COVID-19/complications ; *Postural Orthostatic Tachycardia Syndrome/therapy/etiology ; },
abstract = {RATIONALE: Postural orthostatic tachycardia syndrome (POTS) is a type of autonomic dysfunction that can occur following coronavirus disease (COVID-19) infection, particularly in adolescents. Treatment options are limited and often ineffective. We report a case of long COVID-associated POTS that responded favorably to epipharyngeal abrasive therapy (EAT), a treatment targeting chronic inflammation in the epipharynx.

PATIENT CONCERNS: A previously healthy adolescent developed persistent fatigue, headache, dizziness, insomnia, and orthostatic intolerance lasting over 3 months after a COVID-19 infection. The symptoms severely impaired daily functioning, rendering the patient bedridden.

DIAGNOSES: Based on clinical symptoms and a positive orthostatic test showing excessive postural tachycardia without hypotension, the patient was diagnosed with POTS associated with long COVID. Chronic epipharyngitis was also noted upon endoscopic examination.

INTERVENTIONS: The patient underwent weekly sessions of EAT for a total of 120 days. No additional pharmacologic treatment was provided during this period.

OUTCOMES: The patient showed marked improvement in symptoms, including increased tolerance to standing, reduced fatigue, and improved sleep quality. Objective improvement was confirmed through repeat orthostatic testing. The patient resumed school attendance and daily activities without limitation.

LESSONS: This case highlights the potential effectiveness of EAT in treating long COVID-related POTS in adolescents. EAT may offer a nonpharmacological treatment option by addressing underlying chronic epipharyngeal inflammation, a possible contributor to autonomic dysfunction.},
}

Adolescent
Humans
*COVID-19/complications
*Postural Orthostatic Tachycardia Syndrome/therapy/etiology

@article {pmid40656219,
year = {2025},
author = {Maccarone, MC and Contessa, P and Passarotto, E and Regazzo, G and Masiero, S},
title = {Balance rehabilitation and Long Covid syndrome: effectiveness of thermal water treatment vs. home-based program.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1588940},
pmid = {40656219},
issn = {2673-6861},
abstract = {INTRODUCTION: Balance concerns are increasingly recognized as a common presentation in patients with Long Covid. This study investigates the effects of two distinct rehabilitation programs on balance in a cohort of sixty participants experiencing medium-to-long-term symptoms following SARS-CoV-2 infection.

METHODS: Individuals were enrolled and randomly assigned to either a spa resort rehabilitation program or a supervised home-based rehabilitation program. The study assessed balance and proprioception by analyzing the center of pressure trajectory during a standing task performed with eyes open and closed before, after, and at a 3- and 6-month follow-up after the rehabilitation program.

RESULTS: Results indicated that, right after rehabilitation, participants who enrolled in the home-based program demonstrated more significant improvements in mean stay time and in the standard deviation of oscillations in the antero-posterior direction than those who enrolled in a spa-resort program. On the other hand, at the 3-month follow-up, individuals who enrolled in the spa-resort program exhibited improvements in the standard deviation of oscillations in the antero-posterior direction, indicating ongoing benefits over time.

DISCUSSION: These findings suggest that appropriate rehabilitation programs, whether at home or in spa resorts, can contribute to enhancing overall physical function in these patients.},
}

@article {pmid40656206,
year = {2025},
author = {Weaver, SS and Carry, M and Bertolli, J and Godino, J and Struminger, B and Taren, D and Scott, JD and Sharp, SP and Samaniego, J and Bean, DR and Issa, A and Lin, JS and Unger, ER and Ramers, CB},
title = {Assessing the influence of lived-experience experts on healthcare providers in a virtual community of practice: a qualitative study.},
journal = {Frontiers in health services},
volume = {5},
number = {},
pages = {1562651},
pmid = {40656206},
issn = {2813-0146},
abstract = {Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other poorly understood post-acute infection syndromes (PAIS) can present with unexplained symptoms or conditions that may be misunderstood by healthcare providers, causing delays in diagnosis and care. To address these issues, the Centers for Disease Control and Prevention (CDC) funded the Long COVID and Fatiguing Illness Recovery Program (LC&FIRP), initiated as a pilot project to assess whether providing tele-mentoring and other online education for primary care providers could help them improve the quality of life and support the recovery of their patients with these conditions. The LC&FIRP multi-disciplinary team-based care approach is built on the Extension for Community Healthcare Outcomes (ECHO) learning model, which is an evidence-based virtual learning framework developed by the University of New Mexico and designed to disseminate and implement best practices, especially in under-resourced areas. A distinctive feature of LC&FIRP was the inclusion of lived-experience experts. To explore the influence of lived-experience experts on the care patients received, we collected the educational recommendations provided by the lived-experience experts during webinar sessions (January 2022-March 2024) and grouped these by themes. The major themes that emerged included validation of patients' illness experience; attitudes and beliefs about Long COVID, ME/CFS, and PAIS; understanding patients' challenges and communicating with empathy; navigating referrals; recognizing and supporting disability; and supporting self-care. Investigators also interviewed patients of the Family Health Centers of San Diego (FHCSD) about their experiences receiving care from participating primary care providers and employed content analysis methods to code interview transcripts to identify themes among patients' perspectives. Positive comments from the patients about topics emphasized by the lived-experience experts provided evidence of providers' uptake and application of the experts' recommendations and support the value of involving lived-experience experts in medical education to improve health services.},
}

@article {pmid40656138,
year = {2025},
author = {Dhaouadi, N and Souissi, D and Yacoub, SB and Skhiri, A and Harizi, C and Fakhfakh, R and Boujdaria, R},
title = {Long COVID symptoms in the COVID unit of the emergency Department of Abderrahmen Mami Hospital in Tunisia: prevalence, main symptoms, and associated factors.},
journal = {The Pan African medical journal},
volume = {50},
number = {},
pages = {109},
pmid = {40656138},
issn = {1937-8688},
mesh = {Humans ; Tunisia/epidemiology ; Male ; Female ; Retrospective Studies ; *COVID-19/epidemiology/complications/physiopathology ; Middle Aged ; *Emergency Service, Hospital ; Prevalence ; Risk Factors ; Aged ; Adult ; Cohort Studies ; *Hospitalization/statistics & numerical data ; Aged, 80 and over ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: the COVID-19 pandemic has been evolving since 2019, affecting over 536 million individuals and causing more than six million deaths. After the acute phase, the onset or persistence of symptoms grouped under the name of long COVID is reported. The variability of symptomatology makes this a relevant subject of study, since more than one million cases of COVID-19 have been reported in Tunisia. The aim of our study was to determine the prevalence and potential risk factors for long COVID.

METHODS: we conducted a retrospective cohort study of patients admitted to the COVID unit of the emergency department of Abderrahmane Mami Hospital in Tunisia from April 1st to August 1st, 2021. The National Institute of Health Care definition of long COVID (November 2021) was adopted.

RESULTS: overall, 1,271 patients were admitted during the study period. After excluding deceased and unreachable patients by telephone, 454 were included in the analysis. The mean age was 58.6 ± 13.9 years, with a male predominance (53.7%). The prevalence of long COVID was 84.8%. The most common manifestations were breathing discomfort, asthenia, memory problems, tiredness, and arthralgia. In multivariable analysis, female sex was identified as a risk factor for long COVID (aOR: 1.732, 95% CI 1.002-2.995; p = 0.049).

CONCLUSION: the high prevalence of long COVID observed in our study highlights the need for post-COVID follow-up among affected patients. Our findings suggest that women had a higher risk of developing long COVID, indicating the benefit of individualized monitoring and care programs for this group.},
}

Humans
Tunisia/epidemiology
Male
Female
Retrospective Studies
*COVID-19/epidemiology/complications/physiopathology
Middle Aged
*Emergency Service, Hospital
Prevalence
Risk Factors
Aged
Adult
Cohort Studies
*Hospitalization/statistics & numerical data
Aged, 80 and over
Post-Acute COVID-19 Syndrome

@article {pmid40655185,
year = {2025},
author = {Li, S and Zhao, H and Zhang, M and Yuan, T and Chai, D and Shen, Z and Qin, C and Li, Y and Pan, M},
title = {Long COVID in Elderly COPD Patients: Clinical Features, Pulmonary Function Decline, and Proteomic Insights.},
journal = {International journal of chronic obstructive pulmonary disease},
volume = {20},
number = {},
pages = {2337-2347},
pmid = {40655185},
issn = {1178-2005},
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/physiopathology/diagnosis/complications/epidemiology ; *COVID-19/physiopathology/diagnosis ; Aged ; Male ; Female ; *Proteomics/methods ; *Lung/physiopathology ; SARS-CoV-2 ; Aged, 80 and over ; Time Factors ; Respiratory Function Tests ; Age Factors ; Risk Factors ; *Pneumonia, Viral/physiopathology/diagnosis ; Fatigue/physiopathology ; },
abstract = {BACKGROUND: Elderly patients with chronic obstructive pulmonary disease (COPD) face a heightened risk of developing long coronavirus disease (COVID); however the exact clinical characteristics and underlying mechanisms remain unclear.

METHODS: We enrolled 85 elderly COPD patients, of whom 43 reported newly onset persistent fatigue (the most dominant complaint of long COVID) within 1 year after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and they were allocated to the Long-COVID group. The remaining 42 patients were assigned to the Control group. Patients completed questionnaires, pulmonary function tests, chest CT, routine laboratory tests, and blood proteomic analysis.

RESULTS: Long-COVID patients had a longer course of COPD (> 5 years, 76.8% vs 52.4%) and duration of SARS-CoV-2 infection (10.0 days vs 7.0 days) (All P < 0.05), higher symptom burden, worse pulmonary ventilation function and a more rapid decrease in DLCO (All P < 0.05). Proteomic analysis indicated disruptions in inflammation and energy metabolism, potentially underlying long COVID in these patients. The machine learning model identified wheezing, the duration of SARS-CoV-2 infection, EIF2S3 (eukaryotic translation initiation factor 2 subunit gamma), current FEV1/FVC (%), and the course of COPD as key features distinguishing Long-COVID patients, and exhibited excellent performance.

CONCLUSION: Elderly COPD patients with a longer COPD course and duration of COVID-19 are more prone to develop long COVID, with decreased pulmonary ventilation and diffusion ability. Disordered inflammation regulation and energy metabolism may be the potential mechanisms, highlighting the importance of monitoring inflammation and metabolic dysregulation in elderly COPD patients after recovery from COVID-19.},
}

Humans
*Pulmonary Disease, Chronic Obstructive/physiopathology/diagnosis/complications/epidemiology
*COVID-19/physiopathology/diagnosis
Aged
Male
Female
*Proteomics/methods
*Lung/physiopathology
SARS-CoV-2
Aged, 80 and over
Time Factors
Respiratory Function Tests
Age Factors
Risk Factors
*Pneumonia, Viral/physiopathology/diagnosis
Fatigue/physiopathology