@article {pmid41309532,
year = {2025},
author = {Shakib, SH and Antimisiaris, D},
title = {Analysis of polypharmacy in older adults pre and post COVID-19.},
journal = {Expert review of clinical pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17512433.2025.2596347},
pmid = {41309532},
issn = {1751-2441},
abstract = {BACKGROUND: Increased diagnoses burden is a characteristic of post COVID sequelae. Concomitant increased polypharmacy burden is a consequence yet there are few publications on the topic. The aim of this report is to help characterize post COVID polypharmacy in older adults.

RESEARCH DESIGN AND METHODS: Using data from a large health system, pre and post COVID disease and medication burden was analyzed. Within-person difference was tested. Multiple linear regression determined predictive post COVID increases in clinical burden. Qualitative characterization was supported by multidisciplinary literature review.

RESULTS: In patients ≥61 years the mean increase in diagnoses and medications per post COVID patient was 7.37 and 13.23 respectively. The largest increase in diagnoses was seen in patients aged 71-80 and people of Black race. The largest increase in medications was in patients aged 81-90 and females. Each additional pre-covid diagnosis and medication was associated with a 0.10 unit, and 0.12 unit increase respectively post-COVID-19.

CONCLUSIONS: Each pre-COVID diagnoses and medication were associated with quantifiable increase post-COVID, with higher risk with advanced age, Black race and female gender. Single health system data may inhibit generalizability of our findings. Clinicians should be vigilant and prepared to manage post COVID-19 polypharmacy.},
}

@article {pmid41308689,
year = {2025},
author = {Amdal, CD and Falk, RS and Alanya, A and Schlichting, M and Roychoudhury, S and Bhatnagar, V and Wintner, LM and Regnault, A and Ingelgård, A and Coens, C and le Cessie, S and Holzner, B and Chang, J and Taphoorn, M and Cislo, P and Giesinger, JM and Cappelleri, JC and Pawar, V and Ten Seldam, S and Papadopoulos, EJ and Calvert, MJ and Joseph, KL and Bottomley, A and Griebsch, I and Arraras, JI and Astrup, GL and Basch, E and Belančić, A and Brundage, M and Campbell, A and Rerhou Rantell, K and Cocks, K and Cherny, N and Eremenco, S and Ferrer, M and Fiero, MH and Gerlinger, C and Goetghebeur, E and Grouven, U and Lauer, A and Aiyegbusi, OL and Machingura, A and Mizusawa, J and Molenberghs, G and Aa Petersen, M and Reijneveld, JC and Ringash, J and Rumpold, G and Rutherford, C and Quinten, C and Sail, K and Sasseville, M and Sauerbrei, W and Schiel, A and Smith, AW and Snyder, C and Velikova, G and Wang, XS and Bjordal, K and Pe, M and , },
title = {SISAQOL-IMI consensus-based guidelines to design, analyse, interpret, and present patient-reported outcomes in cancer clinical trials.},
journal = {The Lancet. Oncology},
volume = {26},
number = {12},
pages = {e683-e693},
doi = {10.1016/S1470-2045(25)00520-0},
pmid = {41308689},
issn = {1474-5488},
mesh = {Humans ; *Patient Reported Outcome Measures ; *Neoplasms/therapy/drug therapy ; Consensus ; Quality of Life ; *Research Design/standards ; *Clinical Trials as Topic/standards ; Randomized Controlled Trials as Topic/standards ; },
abstract = {Standardising the implementation of patient-reported outcomes (PROs) in clinical trials is crucial for evaluating the benefits and risks of cancer treatments. The Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) has developed 146 consensus-based recommendations for designing, analysing, interpreting, and presenting PROs in cancer clinical trials. This initiative, undertaken from 2021 to 2025, involved experts, including statisticians, PRO measurement experts, clinicians, and patient representatives from 41 organisations representing regulatory agencies, academia, the pharmaceutical industry, health-technology assessment bodies, and patient advocates. SISAQOL-IMI provides guidance on the implementation of PROs in randomised controlled trials and single-arm trials, terminology, definitions and the selection of PRO score interpretation thresholds, and for visualising PRO results for different audiences. To facilitate the implementation of these standards, in addition to this Policy Review, four key outputs are available: an interactive table, a guidebook, plain language materials, and a glossary.},
}

Humans
*Patient Reported Outcome Measures
*Neoplasms/therapy/drug therapy
Consensus
Quality of Life
*Research Design/standards
*Clinical Trials as Topic/standards
Randomized Controlled Trials as Topic/standards

@article {pmid41305454,
year = {2025},
author = {Miftahof, J and Bernauer, B and Tan, CS},
title = {Neurological Manifestations of SARS-CoV-2.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
doi = {10.3390/v17111432},
pmid = {41305454},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/complications/pathology/virology ; Animals ; *SARS-CoV-2/pathogenicity ; Disease Models, Animal ; Brain/virology/pathology ; *Nervous System Diseases/virology/pathology/etiology ; Central Nervous System/virology/pathology ; },
abstract = {Neurocognitive symptoms have emerged as notable sequelae of SARS-CoV-2 infection (COVID-19). Although primarily a respiratory virus, SARS-CoV-2 has been associated with central nervous system (CNS) changes observed in both clinical and experimental settings. To better understand these effects and their pathological mechanisms, we conducted a systematic literature search of published studies and employed a qualitative, analytical approach to identify and synthesize key findings from peer-reviewed studies, including large-scale retrospective clinical cohorts, human autopsy reports, animal models (murine, non-human primate), and in vitro brain organoid systems. While viral components were detected in post mortem central nervous system tissues, COVID-19 neuropathology appears to stem primarily from immune-mediated inflammation and vascular injury rather than direct CNS infection. Persistent glial activation and BBB disruption may underlie the long-term neurological symptoms reported in long COVID-19. Although animal models offer mechanistic insight, species-specific differences necessitate cautious extrapolation to human pathology. Further investigation into the chronic effects of SARS-CoV-2 on the brain is essential to guide long-term clinical management and therapeutic development.},
}

Humans
*COVID-19/complications/pathology/virology
Animals
*SARS-CoV-2/pathogenicity
Disease Models, Animal
Brain/virology/pathology
*Nervous System Diseases/virology/pathology/etiology
Central Nervous System/virology/pathology

@article {pmid41305428,
year = {2025},
author = {Chiang, KC and Chiu, CEN and Altaf, M and Cheng, MTK and Gupta, RK},
title = {Mechanisms of Cell-Cell Fusion in SARS-CoV-2: An Evolving Strategy for Transmission and Immune Evasion.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
doi = {10.3390/v17111405},
pmid = {41305428},
issn = {1999-4915},
mesh = {Humans ; *SARS-CoV-2/immunology/physiology/pathogenicity/genetics ; *COVID-19/transmission/immunology/virology ; *Immune Evasion ; Cell Fusion ; *Virus Internalization ; Giant Cells/virology ; Animals ; Antibodies, Neutralizing/immunology ; },
abstract = {Early studies on the evolution of SARS-CoV-2 revealed mutations that favored host transmission of the virus and more efficient viral entry. However, cell-free virus spread is vulnerable to host-neutralizing antibodies. As population immunity developed, mutations that confer escape from neutralization were selected. Notably, cell syncytia formation wherein an infected cell fuses with a noninfected cell is a more efficient route of transmission that bypasses humoral immunity. Cell syncytia formation has been implicated in the pathogenicity of SARS-CoV-2 infection whilst compromising host transmission due to impaired whole virion release. Therefore, understanding the mechanisms of virus-mediated cell-cell fusion will aid in identifying and targeting more pathogenic strains of SARS-CoV-2. Whilst the general kinetics of cell-cell fusion have been known for decades, the specific mechanisms by which SARS-CoV-2 induces fusion are beginning to be elucidated. This is partially due to emergence of more reliable, high throughput methods of quantifying and comparing fusion efficiency in experimental models. Moreover, the ongoing inflammatory response and emerging health burden of long COVID may point to cell-cell fusion in the pathogenesis. In this review, we synthesize current understanding of SARS-CoV-2-mediated cell-cell fusion and its consequences on immune escape, viral persistence, and the innate immune response.},
}

Humans
*SARS-CoV-2/immunology/physiology/pathogenicity/genetics
*COVID-19/transmission/immunology/virology
*Immune Evasion
Cell Fusion
*Virus Internalization
Giant Cells/virology
Animals
Antibodies, Neutralizing/immunology

@article {pmid41304297,
year = {2025},
author = {An, M and Dong, X and Gao, Y and Ouyang, J and Ding, H and Zhu, Z and Bao, L and Feng, Y and Tian, W and Wang, P and Han, X and Shang, H},
title = {Immune Suppression, Preexisting Immunity, and Mutation Tendency Shaped SARS-CoV-2 Evolution in Persistent Infection.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112613},
pmid = {41304297},
issn = {2076-2607},
support = {2023YFC3041500//the National Key Research and Development Program of China/ ; 2023-PT320-01//the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; },
abstract = {SARS-CoV-2 evolution in persistent infection, which may induce long COVID-19, is predominantly manifested in immunocompromised hosts, who act as the viral reservoirs for future outbreaks. Therefore, understanding the evolutionary mechanisms of novel variants that can evade preexisting immune responses is critical to guide public health measures and develop vaccines tailored for vulnerable populations. We used next-generation sequencing and phylogenetic methods to delineate the evolutionary and mutational profiles of SARS-CoV-2 variants using serial oropharyngeal swab samples from 5 individuals with persistent infections. Our results revealed that the intra-host evolutionary patterns of different variants varied significantly, and the evolutionary rate in 3 immunocompromised hosts was 20 times higher than in 2 other patients. These variations likely stem from differences in immune suppression status, the strength of preexisting immune responses, and the extent of error-generating mutations. There were 15 intra-host single-nucleotide variants (iSNVs) in the spike gene among at least two variants, suggesting convergent evolution. Although most new iSNVs do not reach fixation, some of them belong to lineage-defined mutations in variants of concern (VOCs) and recent variants of interest (VOIs). The observations indicate that persistent infections serve as sources for novel, potentially harmful variants, whereas the viral evolutionary dynamics are impacted by virological, immunological, and genetic factors. Thus, there is an urgent need for individualized monitoring and management of immunocompromised hosts to prevent outbreaks caused by the viral seeds generated from them and to study viral factors associated with post-acute COVID-19 sequelae.},
}

@article {pmid41304256,
year = {2025},
author = {Mateescu, DM and Ilie, AC and Cotet, I and Guse, C and Muresan, CO and Pah, AM and Badalica-Petrescu, M and Iurciuc, S and Craciun, ML and Avram, A and Margan, MM and Enache, A},
title = {Gut Microbiome Dysbiosis in COVID-19: A Systematic Review and Meta-Analysis of Diversity Indices, Taxa Alterations, and Mortality Risk.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112570},
pmid = {41304256},
issn = {2076-2607},
support = {"Victor Babes" University of Medicine and Pharmacy Timisoara//"Victor Babes" University of Medicine and Pharmacy Timisoara/ ; },
abstract = {COVID-19 is associated with gut microbiome alterations that may influence disease outcomes through immune and inflammatory pathways. This systematic review and meta-analysis evaluated global evidence on gut dysbiosis in COVID-19. We searched PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library up to 5 October 2025 (PROSPERO CRD420251160970). Alpha-diversity indices and microbial taxa log-fold changes (logFC) were analyzed using random-effects models. The pooled standardized mean difference (SMD) for the Shannon index was -0.69 (95% CI -0.84 to -0.54; I[2] = 42%), confirming reduced microbial diversity. Faecalibacterium prausnitzii showed a significant pooled depletion (logFC = -1.24; 95% CI -1.68 to -0.80; k = 10; I[2] = 74%), while Enterococcus spp. was increased (logFC = 1.45; 95% CI 1.12-1.78). Egger's test did not suggest publication bias (p = 0.32). Gut dysbiosis was consistently associated with reduced microbial diversity and enrichment of pathogenic taxa, correlating with increased disease severity and mortality (HR = 1.67). These findings highlight the potential of microbiome profiling as a prognostic tool in COVID-19, although clinical translation requires further validation.},
}

@article {pmid41304215,
year = {2025},
author = {Arruda, ISA and Cavalcante, CDS and Rubens, RS and Castro, LNPF and Nóbrega, YKM and Dalmolin, TV},
title = {Changes in the Gut Microbiota of Patients After SARS-CoV-2 Infection: What Do We Know?.},
journal = {Microorganisms},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/microorganisms13112529},
pmid = {41304215},
issn = {2076-2607},
support = {DPI/BCE nº 01/2025//University of Brasilia/ ; FAPDF nº 09/2023//Fundação de Apoio à Pesquisa do Distrito Federal/ ; },
abstract = {COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut-lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain-gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19.},
}

@article {pmid41303228,
year = {2025},
author = {Al-Zamil, M and Kulikova, NG and Zalozhnev, DM and Shnayder, NA and Petrova, MM and Garganeeva, NP and Zhukova, NG and Tutinina, OV and Naprienko, MV and Smekalkina, LV},
title = {Using the International Index of Erectile Function-15 in Comparative Analysis Between Transcutaneous Electrical Nerve Stimulation of the Pudendal Nerve and Low-Level Laser Therapy in the Treatment of Erectile Dysfunction After COVID-19.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/jcm14228193},
pmid = {41303228},
issn = {2077-0383},
abstract = {Background: Erectile dysfunction (ED) is one of the manifestations of long COVID-19 and in most cases has an endothelial and neurogenic nature. Many experimental and clinical investigations have revealed the high efficacy of transcutaneous electrical nerve stimulation (TENS) of the pudendal nerve and low-level laser therapy (LLLT) in the treatment of ED. Purpose: To compare LLLT and TENS, and investigate the dynamics of their efficacy when combined in the treatment of patients with post-COVID-19 ED using the International Index of Erectile Function-15 (IIEF-15). Materials and Methods: This interventional, randomized controlled trial enrolled 82 patients with ED following COVID-19. All patients had their first ED diagnosis after COVID-19 within one month of the onset of respiratory symptoms. The duration of patients' ED was not less than six months, but less than one year. Patients were divided into four groups, one of which received sham LLLT and TENS (n = 20). The remaining patients underwent effective treatment using LLLT (n = 21), TENS (n = 21), and combined LLLT and TENS (n = 20). To study the effectiveness of the treatment, IIEF-15 and an assessment of tactile sensation in the genital area before and after the treatment, as well as 3 months after the end of the treatment, were used. Results: Both LLLT and TENS had a significant effect in improving erectile function, of 38% (p ≤ 0.01) and 27% (p ≤ 0.01), respectively. The improvement in erectile function after LLLT was higher than after TENS by 8.2% (p ≤ 0.05), but the combination of these methods exceeds the result of using LLLT alone by 20% (p ≤ 0.01). The reduction in hypoesthesia after LLLT did not exceed 17.4% (p ≤ 0.05). However, after TENS, the reduction in hypoesthesia reached 48.7% (p ≤ 0.01), and with a combination of the two methods, it reached 60.9% (p ≤ 0.01). Treatment outcomes in LLLT, TENS, and LLLT + TENS groups were stable for 3 months. Conclusions: According to IIEF-15 dynamics, LLLT and TENS are both very beneficial in treatment of post-COVID-19 ED, with LLLT showing a moderately better outcome than TENS. LLLT and TENS were found to have significant positive therapeutic effects on orgasm, sexual desire, and sexual satisfaction, among other aspects of sexual function. Nevertheless, the combination of LLLT and TENS proved to be much more successful in enhancing all IIEF domains, expanding the therapeutic effect spectrum, and improving the TENS effect following LLLT application. Only after TENS did genital hypoesthesia reliably regress, and the effect was amplified when TENS and LLLT were combined.},
}

@article {pmid41303176,
year = {2025},
author = {Olarinde, F and Nunes-Silva, A and Sanchez-Ramirez, DC and Molgat-Seon, Y and Villar, R},
title = {Using Active Standing Orthostatic Stress Test to Assess Physiological Responses in Individuals with Long COVID: A Systematic Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/jcm14228139},
pmid = {41303176},
issn = {2077-0383},
abstract = {Background/Objectives: Individuals experiencing long COVID (LC) frequently report orthostatic intolerance symptoms, which may be linked to autonomic and cardiovascular dysfunction. The active standing test provides a simple, clinically relevant means to assess these impairments. This systematic review aims to determine the use of the active standing orthostatic stress test in evaluating cardiovascular, autonomic, and respiratory responses in people experiencing LC. Methods: A systematic search, according to PRISMA guidelines, was conducted in PubMed, MEDLINE, EMBASE, CINAHL, and Scopus for articles published between 2020 and 2025. This study was registered in PROSPERO CRD-42024615872. Studies were included if they used the active standing test, enrolled adults (≥18 years), included both long COVID and healthy control groups, used continuous beat-to-beat measurements, and reported physiological outcomes. Risk of bias was assessed using the nine-point Newcastle-Ottawa Scale. Results: Three studies (216 participants experiencing LC and 186 controls) met the inclusion criteria. Across studies, LC individuals consistently exhibited elevated heart rate in both supine and standing positions. However, blood pressure findings were more variable: only one study reported 13% of participants met orthostatic hypotension criteria, while another found significant increases in diastolic blood pressure during standing. Long COVID groups also showed reduced heart rate variability compared to controls. Conclusions: Individuals experiencing LC show elevated heart rate and impaired autonomic function during active standing, with subgroup-specific blood pressure changes. These alterations may contribute to dizziness, fatigue, and reduced activity tolerance. Incorporating active standing into clinical assessment could aid early identification of autonomic dysfunction and inform rehabilitation strategies, though more research is urgently needed.},
}

@article {pmid41302967,
year = {2025},
author = {Alghamdi, F and Meertens, R and Obotiba, AD and Harries, LW and Appleby, S and Mokbel, K and Knapp, KM and Strain, WD},
title = {Assessment of Health-Related Quality of Life and Biomarkers in Long COVID: A 12-Month Longitudinal Feasibility Cohort.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
doi = {10.3390/jcm14227931},
pmid = {41302967},
issn = {2077-0383},
support = {part of PhD project//Qassim University/ ; },
abstract = {Background/Objectives: Long COVID (LC) causes persistent symptoms, including fatigue, musculoskeletal (MSK) pain, and a lower quality of life. It is hypothesised that chronic low-grade inflammation in LC could impact bone, joints, and muscle microcirculation, but evidence is limited. Our aim is to assess health-related quality of life (HRQoL) and circulating inflammation, bone turnover markers (BTM), and vitamin D in LC individuals to explore their potential association with MSK function. Methods: Prospective longitudinal cohort; LC n = 45, well-recovered (WR) n = 40; 12 ± 2 months follow-up. Baseline and follow-up assessments included evaluations of HRQoL and pain-rating questionnaires, and blood analysis of inflammatory and bone turnover markers (BTM). Results: More females were in the LC group. LC reported significantly lower HRQoL compared to WR, with no change over 12 months. LC had higher vitamin D levels at baseline, median 29.46 ng/mL (23.75; 35.06) compared to WR 20.36 ng/mL (15.995; 27.65) (p = 0.0021). Both groups experienced significant increases in vitamin D after 12 months: WR median from 21.4 ng/mL (16.34; 27.89) to 29.58 ng/mL (25.33; 41.74), (p =< 0.001) and LC median from 32.695 ng/mL (23.665; 35.1) to 35.89 ng/mL (30.1; 41.2), (p = 0.0023). Pain rating showed LC also experienced more hand pain at baseline median 1 (0; 5), (p = 0.003). There were no differences between groups in BTM or cytokines over time. Conclusions: This feasibility cohort showed that LC is associated with a reduction in HRQoL and joint symptoms; however, no significant changes were observed in the inflammatory markers, indicating the need for ongoing monitoring. Future studies should explore MSK, muscle function via imaging, and ways to enhance musculoskeletal health and well-being.},
}

@article {pmid41302639,
year = {2025},
author = {Perestiuk, V and Sverstyuk, A and Kosovska, T and Volianska, L and Boyarchuk, O},
title = {A Predictive Model for the Development of Long COVID in Children.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
doi = {10.3390/ijerph22111693},
pmid = {41302639},
issn = {1660-4601},
support = {0123U100301//Ministry of Health of Ukraine/ ; },
mesh = {Humans ; Child ; *COVID-19/epidemiology/complications ; Child, Preschool ; Infant ; Male ; Female ; Adolescent ; Cross-Sectional Studies ; Risk Factors ; SARS-CoV-2 ; *Models, Theoretical ; },
abstract = {BACKGROUND/OBJECTIVES: Machine learning is an extremely important issue, considering the potential to prevent the onset of long-term complications from coronavirus disease or to ensure timely detection and effective treatment. The aim of our study was to develop an algorithm and mathematical model to predict the risk of developing long COVID in children who have had acute SARS-CoV-2 viral infection, taking into account a wide range of demographic, clinical, and laboratory parameters.

METHODS: We conducted a cross-sectional study involving 305 pediatric patients aged from 1 month to 18 years who had recovered from acute SARS-CoV-2 infection. To perform a detailed analysis of the factors influencing the development of long-term consequences of coronavirus disease in children, two models were created. The first model included basic demographic and clinical characteristics of the acute SARS-CoV-2 infection, as well as serum levels of vitamin D and zinc for all patients from both groups. The second model, in addition to the aforementioned parameters, also incorporated laboratory test results and included only hospitalized patients.

RESULTS: Among 265 children, 138 patients (52.0%) developed long COVID, and the remaining 127 (48.0%) fully recovered. We included 36 risk factors of developing long COVID in children (DLCC) in model 1, including non-hospitalized patients, and 58 predictors in model 2, excluding them. These included demographic characteristics of the children, major comorbid conditions, main symptoms and course of acute SARS-CoV-2 infection, and main parameters of complete blood count and coagulation profile. In the first model, which accounted for non-hospitalized patients, multivariate regression analysis identified obesity, a history of allergic disorders, and serum vitamin D deficiency as significant predictors of long COVID development. In the second model, limited to hospitalized patients, significant risk factors for long-term sequelae of acute SARS-CoV-2 infection included fever and the presence of ≥3 symptoms during the acute phase, a history of allergic conditions, thrombocytosis, neutrophilia, and altered prothrombin time, as determined by multivariate regression analysis. To assess the acceptability of the model as a whole, an ANOVA analysis was performed. Based on this method, it can be concluded that the model for predicting the risk of developing long COVID in children is highly acceptable, since the significance level is p < 0.001, and the model itself will perform better than a simple prediction using average values.

CONCLUSIONS: The results of multivariate regression analysis demonstrated that the presence of a burdened comorbid background-specifically obesity and allergic pathology-fever during the acute phase of the disease or the presence of three or more symptoms, as well as laboratory abnormalities including thrombocytosis, neutrophilia, alterations in prothrombin time (either shortened or prolonged), and reduced serum vitamin D levels, are predictors of long COVID development among pediatric patients.},
}

Humans
Child
*COVID-19/epidemiology/complications
Child, Preschool
Infant
Male
Female
Adolescent
Cross-Sectional Studies
Risk Factors
SARS-CoV-2
*Models, Theoretical

@article {pmid41302566,
year = {2025},
author = {Sui, SX and Yu, L},
title = {Patient and Professional Perspectives on Long COVID: A Systematic Literature Review and Meta-Synthesis.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
doi = {10.3390/ijerph22111620},
pmid = {41302566},
issn = {1660-4601},
mesh = {Humans ; *COVID-19/psychology ; *Health Personnel/psychology ; SARS-CoV-2 ; Qualitative Research ; },
abstract = {BACKGROUND: Post-COVID-19 condition ('long COVID') involves fluctuating symptoms across multiple organ systems and disability or functional loss, which may be episodic, continuous, or permanent. Qualitative research is essential to capture lived experiences and explain how social and health system contexts may influence improvement, recovery, and service use. We synthesised perspectives from people living with long COVID and healthcare professionals to inform service design and policy.

METHODS: We conducted a systematic review and qualitative meta-synthesis. MEDLINE, Embase, PsycINFO, CINAHL, Scopus, and Web of Science were searched for studies published between 1 January 2020 and 19 August 2025. Eligible studies reported qualitative data from adults with long COVID (≥12 weeks after acute infection) and/or healthcare professionals in any setting. We excluded non-qualitative, non-primary, or non-English reports. Two reviewers independently screened, extracted, and appraised studies using the Critical Appraisal Skills Programme checklist. Data were synthesised thematically. The protocol was registered with the Open Science Framework.

FINDINGS: Of 1544 records screened, 49 studies met the inclusion criteria: 41 involving patients, two involving professionals, and six involving both. Eight patient themes (including symptom burden, identity disruption and stigma) and four professional themes (including recognition, care coordination and holistic care models) were identified. Recognition emerged as a cross-cutting mechanism: validation and consistent pacing guidance facilitated engagement and safer activity, whereas invalidation and inconsistent advice were associated with distress, avoidance, and disengagement. Trajectories showed gradual expansion of multidisciplinary care models, but major capacity and equity gaps persisted. Most studies had low methodological concerns, although heterogeneity in populations and settings was substantial.

INTERPRETATION: Long COVID is a chronic, biological condition that also intersects with social and psychological dimensions, and may present with episodic, continuous, or progressive trajectories. Healthcare services must prioritise early validation, provide consistent pacing and relapse prevention guidance, expand access to multidisciplinary and peer-supported rehabilitation, integrate mental healthcare, strengthen coordinated pathways, and support graded return to work. Explicit attention to equity is required to avoid widening disparities.},
}

Humans
*COVID-19/psychology
*Health Personnel/psychology
SARS-CoV-2
Qualitative Research

@article {pmid41301920,
year = {2025},
author = {Knauer, TS and Mardin, CY and Rech, J and Michelson, G and Stog, A and Zott, J and Steußloff, F and Güttes, M and Sarmiento, H and Ilgner, M and Jakobi, M and Hohberger, B and Schottenhamml, J},
title = {Evaluation of Stereopsis Performance, Gaze Direction and Pupil Diameter in Post-COVID Syndrome Using Machine Learning.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112828},
pmid = {41301920},
issn = {2227-9059},
support = {2490-PC-2021-V14//Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit/ ; GRK 2504/1//Deutsche Forschungsgemeinschaft/ ; 01EO2105//Bundesministerium für Forschung, Technologie und Raumfahrt/ ; },
abstract = {Background/Objectives: Post-COVID syndrome (PCS) encompasses symptoms that persist for at least 12 weeks after the onset of a COVID-19 infection and cannot be explained by other causes. The most common symptoms are fatigue, cognitive impairments, and physical limitations. The objective diagnosis of PCS is still challenging, as specific biomarkers are lacking. One possibility to measure cognitive impairment is the virtual-reality-oculomotor-test-system (VR-OTS, Talkingeyes & More, Germany). It shows stereoscopic stimuli in a VR-environment to the test person. While working on the visual tasks, many features are recorded. These features can be categorized into three groups: stereopsis performance, gaze direction, and pupil diameter. The aim of this study was to investigate which of these three feature groups is best to distinguish patients with PCS from a healthy control group. Methods: In total, 429 patients with PCS were recruited within the disCOVer 1.0 and disCOVer 2.0 study at the Department of Ophthalmology, Universitätsklinikum (Erlangen, Germany). All patients received VR-OTS measurements. From these measurements, a total of 95 features were extracted, which can be categorized into three groups: gaze direction, pupil diameter, and stereopsis performance. In the first step, support vector machines (SVMs) were trained on these different feature sets and evaluated using the area under receiver operating characteristic (AUROC) as the evaluation metric. In the second step, the same procedure was repeated with each feature independently to investigate which were most the predictive per group. Results: The SVM using the pupil diameter features yielded an AUROC of 0.73, the one using the gaze direction features resulted in an AUROC of 0.68. and the stereopsis performance features produced an AUROC of 0.66. The SVM using all VR-OTS data showed an AUROC of 0.68. For the single features, the index of pupillary activity (IPA) showed the best discrimination. Moreover, all features that were evaluated at different difficulties showed the same pattern-that the more difficult test proved to be more predictive. Conclusions: The study showed that VR-OTS can distinguish between patients with PCS and healthy control probands. Since different features showed a better performance than others, it makes sense for further studies to use a subset of the available features for further analysis.},
}

@article {pmid41301889,
year = {2025},
author = {Ivanovska, M and Homadi, MS and Angelova, G and Taskov, H and Murdjeva, M},
title = {Differential Characteristics and Comparison Between Long-COVID Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112797},
pmid = {41301889},
issn = {2227-9059},
abstract = {Long-COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are disabling diseases characterised by ongoing fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome typically follows viral infections, whereas Long-COVID exclusively follows SARS-CoV-2 infection, with overlapping but distinct features. This review uses comprehensive searches of online databases to compare their clinical presentations, pathophysiologies, and treatments. Both Long-COVID and ME/CFS appear to involve multifactorial mechanisms, including viral persistence, immune dysregulation, endothelial dysfunction, and autoimmunity, though their relative contributions remain uncertain. Symptom management strategies are consistent, however. Cognitive behaviour therapy has been successful, and there are minimal drug treatments. Graded exercise therapy occupies a contested place, recommending individualised pacing and multidisciplinary rehabilitation. Common and exclusive mechanisms must be identified to formulate valuable therapies. A more significant body of research focusing on immune dysfunction as a pathogenic mechanism for advancing the disease and enabling more effective therapies and diagnostics is needed.},
}

@article {pmid41301758,
year = {2025},
author = {García-Onrubia, J and Vazirani, R and Feltes, G and Sánchez-Del Hoyo, R and Viana-Llamas, MC and Raposeiras-Roubín, S and Romero, R and Alfonso-Rodríguez, E and Uribarri, A and Santoro, F and Becerra-Muñoz, V and Pepe, M and Castro-Mejía, AF and Signes-Costa, J and Gonzalez, A and Marín, F and Lopez-País, J and Cerrato, E and Vázquez-Cancela, O and Espejo-Paeres, C and López Masjuan, Á and Velicki, L and El-Battrawy, I and Ramakrishna, H and Fernandez-Ortiz, A and Nuñez-Gil, IJ},
title = {The Long-Term Outcomes of Corticosteroid Use in COVID-19 Patients with Cardiovascular Disease: A Propensity-Matched Analysis from the Multi-Center International Prospective Registry (HOPE-2).},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112665},
pmid = {41301758},
issn = {2227-9059},
abstract = {Introduction: Corticosteroid therapy has been demonstrated to improve prognosis and reduce mortality in patients with severe Coronavirus Disease 2019 (COVID-19) infection by attenuating the exaggerated inflammatory response that emerges in the late phase of infection. However, its impact on patients with pre-existing cardiovascular disease, who are at higher risk of complications, has not been specifically studied. The aim of this study is to evaluate the effect of corticosteroid therapy on mortality and long-term COVID-19 symptoms in this high-risk population. Methods: We analyzed the prospective registry HOPE-2. Patients with previous cardiovascular disease were selected, and 18-month all-cause death was defined as the primary endpoint. Long-term COVID-19 symptoms were considered as secondary endpoints. A total of 1188 patients with previous heart disease were included, of which 453 received corticosteroid treatment. Propensity score matching analysis in a 1:1 fashion was performed based on baseline variables that exhibited a p-value < 0.05 in the univariant analysis and outcome variables that defined corticosteroid use, with a final matched population of 796 patients. Results: In patients with pre-existing heart disease, corticosteroid treatment was not associated with differences in 18-month all-cause mortality (p = 0.52). However, a shorter duration of hospitalization (median: 8 days [IQR: 4-14] and 11 days [IQR: 7-18]; p < 0.001) was observed in patients who received corticosteroids. No significant differences in long-term COVID-19 symptoms were observed between the two groups. Conclusions: In patients with pre-existing heart disease, the absence of a clear harmful effect suggests that the positive effects of corticosteroids may be offset by their potential adverse effects which could contribute to the persistence of long COVID symptoms. This finding may reflect a differential response to corticosteroids in this high-risk subgroup, highlighting the need for further studies to clarify the role of this therapy in such patients.},
}

@article {pmid41301729,
year = {2025},
author = {Quach, TC and Wilson, A and Sum-Ping, O and Lomba, S and Geng, LN and Shafer, R and Miglis, MG and Yang, PC and Grossman, L and Ricciardiello, G and Bonilla, H},
title = {Can Low Cortisol Predict Long COVID? A Controversial Issue.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biomedicines13112636},
pmid = {41301729},
issn = {2227-9059},
abstract = {Cortisol dysregulation has been proposed as a biomarker of long COVID (LC), but findings remain inconsistent. Prior reports suggested low cortisol levels in LC, yet collection times and study designs varied substantially. To evaluate morning serum cortisol distributions in an independent LC cohort, accounting for circadian timing and sleep patterns, we performed a retrospective cross-sectional study of consecutive adults seen at the Stanford Long COVID Clinic between 14 February 2022 and 31 July 2024 (IRB #62996). Eligible participants had confirmed SARS-CoV-2 infection, symptoms persisting ≥3 months per NASEM criteria, completion of the Alliance Sleep Questionnaire (ASQ), and a morning serum cortisol measured using the Roche Elecsys[®] Cortisol II assay. Analyses were restricted to collections between 05:00-10:00, categorized as early morning peak (EMP: 05:00-08:00) or mid-morning (MMP: 08:01-10:00). Cortisol was classified as low (<6.2 μg/dL), normal (6.2-19.4 μg/dL), or elevated (>19.4 μg/dL). Among 86 LC patients (69.8% female; mean age 45.4 ± 12.9 years), the mean serum cortisol level was 15.67 ± 6.76 μg/dL. Overall, 62.8% of patients had cortisol within the reference range, 36.0% had elevated levels, and only 1.2% (n = 1) had a low value. Cortisol distributions were comparable across the EMP and MMP collection windows, with no statistically significant differences observed by sleep alignment. Inflammatory markers, including CRP and D-dimer, were largely within reference ranges across all cortisol strata. Contrary to earlier reports, low morning cortisol was rare in this LC cohort; most values were normal or elevated. Findings underscore the importance of circadian timing when interpreting cortisol in LC and highlight the need for prospective studies with serial measurements to determine biomarker utility.},
}

@article {pmid41300187,
year = {2025},
author = {Pour Mohammadi, S and Etesamipour, R and Mercado Romero, F and Noroozi Fashkhami, M and Peláez, I},
title = {Physical Symptoms and Neurocognitive Complaints in Long COVID: Associations with Gender, Age, Education, and Clinical Factors.},
journal = {Brain sciences},
volume = {15},
number = {11},
pages = {},
doi = {10.3390/brainsci15111180},
pmid = {41300187},
issn = {2076-3425},
abstract = {Long COVID is frequently accompanied by neurocognitive complaints, yet the combined effects of demographic and clinical factors remain unclear. This study examined individuals six months after their most recent SARS-CoV-2 infection using a Demographic/Infection-History form, a Physical and Neurocognitive Symptom Checklist (binary), and the Post-COVID Cognitive Impairment Scale (memory, attention; 5-point Likert). Participants were recruited through convenience sampling from multiple community and online sources. Inclusion criteria required confirmed prior COVID-19 infection, self-perceived or clinically documented Long COVID symptoms, and no history of neurological or severe psychiatric disorders. The final sample consisted of 212 participants (mean age = 39.7 years, SD = 10.5), of whom 67.9% were female, and most held a master's (35.4%) or bachelor's (28.3%) degree. Difficulties with retaining new information (57.8%) and concentrating (52.1%) were the most frequent neurocognitive complaints, while severe fatigue after mild activity (23.2%) and chronic fatigue (22.7%) were the most common physical symptoms. Confusion and decision-making difficulty were more frequent among younger participants; women reported greater difficulty retaining new information, and difficulty concentrating varied by education level. A multivariable regression model explained 7% of the variance in total cognitive complaints, identifying education level (β = -0.18, p < 0.01) and number of physical symptoms (β = 0.19, p < 0.01) as significant predictors. Higher educational attainment was associated with fewer cognitive complaints, whereas a greater burden of physical symptoms predicted higher complaint scores. Persistent cognitive difficulties in Long COVID appear closely related to physical symptom burden and protective factors such as education, rather than to infection frequency or sensory dysfunction duration. Findings highlight the need for routine cognitive screening, fatigue-focused management, and longitudinal multimodal research to elucidate underlying mechanisms and recovery pathways.},
}

@article {pmid41299665,
year = {2025},
author = {Dalle Carbonare, L and Minoia, A and Zouari, S and Braggio, M and Cominacini, M and Gaglio, SC and Piritore, FC and Lorenzi, P and Meneghel, M and Dervishi, K and Corsi, A and Pedrinolla, A and Giuriato, G and Fiore, A and Celesia, A and Guerricchio, L and Venturelli, M and Schena, F and Donadelli, M and Mottes, M and Romanelli, MG and Perduca, M and Guardavaccaro, D and Crisafulli, E and Zipeto, D and Barile, L and Valenti, MT},
title = {Extracellular vesicles from long COVID patients promote RUNX2-mediated cellular stress via dysregulated miR-204 and p53 pathway activation.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {508},
pmid = {41299665},
issn = {1478-811X},
support = {Excellence Project 2023-2027 of the Department of Neuroscience, Biomedicine and Movement Sciences of the University of Verona//MUR/ ; PRIN 2022 - Projects of Relevant National Interest, funded by the European Union - NextGenerationEU, PNRR, Mission 4, Component 2, Investment 1.1, project Title "Fine definition of systemic and mucosal response in SARS-CoV-2 vaccinated subjects" - CUP code B53D23003410006.//MUR/ ; },
mesh = {Humans ; *Extracellular Vesicles/metabolism ; *MicroRNAs/metabolism/genetics ; *Tumor Suppressor Protein p53/metabolism ; *COVID-19/metabolism/pathology ; *Core Binding Factor Alpha 1 Subunit/metabolism/genetics ; Human Umbilical Vein Endothelial Cells/metabolism ; Signal Transduction ; SARS-CoV-2 ; Female ; Male ; Mesenchymal Stem Cells/metabolism ; Stress, Physiological ; },
abstract = {BACKGROUND: Subjects with Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), experience a wide range of symptoms, including fatigue and respiratory disturbances, affecting their quality of life. Despite the increasing prevalence of Long COVID, the underlying pathogenic mechanisms remain poorly understood. Extracellular vesicles (EVs) are known to be involved in various processes, such as tissue repair and the transmission of viral particles. However, the specific characteristics and functional roles of EVs derived- from patients with Long COVID (LC-EVs) are poorly characterized.

METHODS: To uncover systemic mechanisms underlying Long COVID, we performed a comprehensive characterization of patient-derived extracellular vesicles (EVs) via Nanoparticle Tracking analysis (NTA), Atomic Force Microscopy (AFM), Transmission Electron Microscope (TEM) and flow cytometry. These EVs were applied to lung cells, Mesenchymal Stem Cell (MSCs), Human Umbilical Vein Endothelial Cells (HUVECs) and Aortic Smooth Muscle Cells (ASMCs), revealing stress responses through SESN1, SESN2, and p53 activation. We further assessed mitochondrial respiration to evaluate metabolic dysfunction, and conducted targeted transfection experiments to dissect the molecular pathways involved, shedding light on EV-driven cellular reprogramming.

RESULTS: Thus, we observed that Long COVID (LC) patients experienced breathlessness and leg discomfort during exertion. Our data highlighted that LC-EVs induce aberrant RUNX2 expression and activate the p53/p21 pathway in lung cells as well stress responses. Additionally, LC-EVs impair mitochondrial function and cellular adaptability under metabolic stress, reducing maximal respiration and ATP production at high cell densities. Protein interaction analysis showed RUNX2 involvement in key biological processes and post-transcriptional regulation by hsa-miR-204-5p was identified. Finally, LC-EVs also activated stress pathways and increased RUNX2, SESN, p53, and p21 levels in endothelial cells, aortic smooth muscle cells, and mesenchymal stem cells.

CONCLUSIONS: In conclusions, these findings provide new insights into the role of extracellular vesicles in Long COVID, revealing their involvement in cellular stress and impaired mitochondrial function.},
}

Humans
*Extracellular Vesicles/metabolism
*MicroRNAs/metabolism/genetics
*Tumor Suppressor Protein p53/metabolism
*COVID-19/metabolism/pathology
*Core Binding Factor Alpha 1 Subunit/metabolism/genetics
Human Umbilical Vein Endothelial Cells/metabolism
Signal Transduction
SARS-CoV-2
Female
Male
Mesenchymal Stem Cells/metabolism
Stress, Physiological

@article {pmid41299639,
year = {2025},
author = {Gamillscheg-Müllner, P and Łaszewska, A and Hoffmann, K and Simon, J and Mayer, S},
title = {Barriers, facilitators, and the role of central coordination: understanding long COVID-19 healthcare access in a universal healthcare system.},
journal = {Archives of public health = Archives belges de sante publique},
volume = {83},
number = {1},
pages = {286},
pmid = {41299639},
issn = {0778-7367},
support = {SO68900010//Medical University of Vienna and the University of Vienna/ ; SO68900010//Medical University of Vienna and the University of Vienna/ ; SO68900010//Medical University of Vienna and the University of Vienna/ ; },
}

@article {pmid41295749,
year = {2025},
author = {Westman, H and Hammarström, P and Nyström, S},
title = {SARS-CoV-2 Spike Protein Amyloid Fibrils Impair Fibrin Formation and Fibrinolysis.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00550},
pmid = {41295749},
issn = {1520-4995},
abstract = {Long COVID, or postacute sequelae of COVID-19 from SARS-CoV-2 infection, is a persistent debilitating disease affecting multiple systems and organs. Long COVID pathophysiology is a complex and not fully established process. One prevailing theory is that the formation of fibrin amyloid microclots (fibrinaloids), due to SARS-CoV-2 infection, can induce persistent inflammation and capillary blockage. An association between the amyloidogenic Spike protein of SARS-CoV-2 and impaired fibrinolysis was made when it was observed that fibrin clots formed in the presence of a mixture of amyloid fibrils from the spike protein mediated resistance to plasmin lysis. Here, we use purified components from the coagulation cascade to investigate the molecular processes of impaired fibrinolysis using seven amyloidogenic SARS-COV-2 Spike peptides. Five of seven Spike amyloid fibrils appeared not to substantially interfere with the fibrinogen-fibrin-fibrinolysis process in vitro, while two spike fibrils were active in different ways. Spike601 amyloid fibrils (sequence 601-620) impaired thrombin-mediated fibrin formation by binding and sequestering fibrinogen but did not affect fibrinolysis. On the contrary, fibrin clots formed in the presence of Spike685 amyloid fibrils (sequence 685-701) exhibited a marked resistance to plasmin-mediated fibrinolysis. We conclude that Spike685 amyloid fibrils can induce dense fibrin clot networks as well as incorporate fibrin into aggregated structures that resist fibrinolysis. Our study proposes a molecular mechanism for how the Spike protein of SARS-CoV-2 could contribute to the formation of fibrinolysis-resistant microclots observed in long COVID.},
}

@article {pmid41293716,
year = {2025},
author = {Mancini, DM and Brunjes, DL and Cook, D and Soto, T and Blate, M and Quan, P and Yamazaki, T and Norweg, A and Natelson, BH},
title = {Abnormal breathing patterns and hyperventilation are common in patients with chronic fatigue syndrome during exercise.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1669036},
pmid = {41293716},
issn = {2296-858X},
abstract = {INTRODUCTION: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience symptoms of fatigue, dyspnea, mental fog, and worsening fatigue after physical or mental efforts. Some of these patients have been found to hyperventilate. In long COVID patients, many of whom also have ME/CFS, dysfunctional breathing (DB) has been described. Whether patients with ME/CFS, independent of COVID-19, experience dysfunctional breathing is unknown, as well as how it may relate to hyperventilation.

METHODS: We performed serial 2-day cardiopulmonary exercise testing (CPET) in 57 patients with ME/CFS and 25 age- and activity-matched control participants. Peak oxygen consumption (VO2), ventilatory efficiency slope (VE/VCO2), O2 saturation, end-tidal CO2 (PetCO2), heart rate, and mean arterial blood pressure were measured in all patients during upright incremental bicycle exercise. Ventilatory patterns were reviewed using minute ventilation (VE) versus time, respiratory rate, and tidal volume versus minute ventilation graphs. Chronic hyperventilation (HV) was defined as a PETCO2 of <34 mm Hg that persisted during low-intensity exercise. Dysfunctional breathing was characterized by a 15% increase in oscillations in minute ventilation during at least 60% of the exercise duration or by a scatterplot pattern of respiratory rate and tidal volume plotted versus minute ventilation.

RESULTS: The patients with ME/CFS had an average age of 38.6 ± 9.6 years, and a mean body mass index (BMI) of 24.1 ± 3.4, which was comparable to the sedentary controls. All participants performed maximal exercise, achieving a respiratory exchange ratio (RER) of >1.05. For the patients with ME/CFS, peak VO2 averaged 22.3 ± 5.3 mL/kg/min, which was 79 ± 20% of predicted and comparable to that observed in the sedentary controls (23.4 ± 4.6 mL/kg/min; 81 ± 12%; p = NS). A total of 24 patients with ME/CFS (42.1%) met the criteria for dysfunctional breathing compared to four sedentary controls (16%) (p < 0.02). In total, 18 patients with ME/CFS (32%) had hyperventilation compared to one sedentary control participant (4%) (p < 0.01), and nine patients with ME/CFS had both hyperventilation and dysfunctional breathing, whereas no sedentary participant exhibited both. The patients with ME/CFS and hyperventilation had significantly higher VE/VCO2 ratios (HV+: 34.7 ± 7.2; HV-: 28.1 ± 3.8; p < 0.001). A total of 15 of 18 patients with hyperventilation (83%) had either elevated VE /VCO2 ratios (n = 15) or dysfunctional breathing (n = 9) compared to 44% (n = 17) of the 40 non-hyperventilators (p < 0.01).

CONCLUSION: Dysfunctional breathing and hyperventilation are common in patients with ME/CFS and could present a new therapeutic target for these patients.},
}

@article {pmid41293426,
year = {2025},
author = {Sørensen, L and Agergaard, J and Nielsen, TB and Schiøttz-Christensen, B and Laursen, CH and Leth, S and Nielsen, CV and Oestergaard, LG},
title = {Construct validity of self-reported and interview-guided administration methods of the Danish version of the post-COVID-19 functional Status scale.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1690892},
pmid = {41293426},
issn = {2673-6861},
abstract = {INTRODUCTION: The Post-COVID-19 Functional Status (PCFS) scale was quickly adopted into COVID-19 research and clinical practice worldwide to monitor functional status and recovery. The scale has been translated into Danish, and three different administration methods have been employed. However, clinicians have expressed concerns about the scale's ability to capture work-related functional limitations. Therefore, the purpose of this study was to evaluate the construct validity of three different administration methods of the Danish version of the PCFS scale.

METHODS: This cross-sectional study included patients with long COVID who completed three versions of the PCFS scale: a questionnaire-based version, a flowchart-based version, and an interview-based version. The construct validity was evaluated following the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines by testing predefined hypotheses that compared the PCFS scale with sick leave and EuroQoL Five-dimensions Five level (EQ-5D-5l).

RESULTS: A total of 437 patients, with a mean age 48 years, 75% female, and 59% on sick leave, were included in this study. Statistically significant differences between the three administration methods were found. Of the 234 patients on sick leave, only 50%-54% had a PCFS grade ≥3 which was below our predefined hypothesis. Furthermore, correlations between the PCFS scale and EQ-5D-5l was lower than hypothesized.

CONCLUSION: None of the three administration methods effectively captured work-related functional limitations associated with being on part-time or full-time sick leave. Additionally, correlations with quality of life were lower than expected. Overall, the construct validity of the PCFS scale was only partially supported.},
}

@article {pmid41291987,
year = {2025},
author = {Rhodes, S and Tutbury, M},
title = {Suggestions for managing long Covid in primary care in Aotearoa New Zealand: a qualitative study.},
journal = {Journal of primary health care},
volume = {},
number = {},
pages = {},
doi = {10.1071/HC25143},
pmid = {41291987},
issn = {1172-6156},
abstract = {Introduction In Aotearoa New Zealand, the responsibility for management of long Covid sits with primary care. GPs are often the first point of contact for these patients in a system that is already overburdened. Globally, patient experiences of accessing support for long Covid are varied. To date, the perspectives of New Zealanders living with the condition, on how best to support their care, have not been sought. Aim The aim of this study is to explore what a long Covid service should offer from the perspectives of those living with the condition. Methods Participants were recruited via the New Zealand long haulers Facebook group and individual interviews and discussions were conducted using Zoom. These were semi-structured with a few loosely structured questions to encourage discussion. Data were analysed using Braun and Clarke's thematic analysis. Results Eighteen participants were recruited. Four themes were identified in the data: practical guidance to support the health care journey; training and collaboration between health professionals; personalised care; and opportunity for health system change. Discussion Overall, participants appeared to want interdisciplinary knowledge sharing; collaborative services with clear lines of communication and a person-centred approach to care. Many of these proposed suggestions for a long Covid clinic align with the Ministry of Health recommendations. However, to date, there is no addition support from Government to support these long Covid service recommendations.},
}

@article {pmid41286763,
year = {2025},
author = {Assavanopakun, P and Wangkawong, S and Kiratipaisarl, W and Sirikul, W and Promkutkao, T and Promkutkeo, S and Kitro, A},
title = {The hidden burden: prevalence and risk factors of long COVID among university students in Chiang Mai, Thailand.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {4123},
pmid = {41286763},
issn = {1471-2458},
support = {No.074/2566//Faculty of Medicine, Chiang Mai University/ ; },
mesh = {Humans ; Thailand/epidemiology ; Female ; *COVID-19/epidemiology ; *Students/statistics & numerical data ; Male ; Cross-Sectional Studies ; Universities ; Prevalence ; Young Adult ; Risk Factors ; Adult ; Surveys and Questionnaires ; Adolescent ; COVID-19 Vaccines/administration & dosage ; SARS-CoV-2 ; },
abstract = {BACKGROUND: As the COVID-19 pandemic transitions to an endemic phase, long COVID symptoms following SARS-CoV-2 infection have emerged as a new global health challenge. However, its impact on university students remains underexplored. This study aimed to assess the prevalence of long COVID symptoms and identify its predictive factors.

METHODS: A cross-sectional study was conducted from February to August 2023 among Thai university students in Chiang Mai. An online questionnaire collected data on demographics, COVID-19 history, vaccination, and health status. Multivariable binary logistic regression was used to identify factors associated with long COVID.

RESULTS: A total of 997 students participated (60.5% female, mean age 20.6 years). Of these, 60.9% had received at least three COVID-19 vaccine doses, and 21.4% had received more than three mRNA vaccine doses. The prevalence of long COVID symptoms was 21.9% (n = 218). Common symptoms included respiratory issues (54.6%), neurological complaints (50.4%), psychological symptoms (42.7%), and poor sleep quality (34.9%). Significant predictors of long COVID included severe initial infection (aOR = 15.3; 95% CI: 5.3-44.3; p < 0.001), longer illness duration (aOR = 1.05; 95% CI: 1.0-1.1; p = 0.031), and poor sleep quality (aOR = 2.1; 95% CI: 1.4-3.1). Each additional dose of mRNA vaccine reduced the likelihood of severe outcomes by 14% (aOR = 0.86; 95% CI: 0.8-1.0; p = 0.044).

CONCLUSION: A minority of Thai university students reported long COVID symptoms. Vaccination, especially with multiple mRNA doses, was linked to reduced risk. Early detection and targeted support during recovery may help mitigate long-term health consequences in this group.},
}

Humans
Thailand/epidemiology
Female
*COVID-19/epidemiology
*Students/statistics & numerical data
Male
Cross-Sectional Studies
Universities
Prevalence
Young Adult
Risk Factors
Adult
Surveys and Questionnaires
Adolescent
COVID-19 Vaccines/administration & dosage
SARS-CoV-2

@article {pmid41286257,
year = {2025},
author = {Staab, KR and McIntosh, MJ and Puliyakote, ASK and Hahn, AD and AlArab, N and Percy, JL and Lanning, T and Theeler, J and Linkenmeyer, C and Wharff, CJ and Bruening, E and Sieren, JC and Hoffman, EA and Comellas, AP and Hoth, KF and Fain, SB},
title = {Long COVID: lung pathophysiology and its relationship with cognitive dysfunction.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-26568-y},
pmid = {41286257},
issn = {2045-2322},
support = {NIH NCATS S10OD026960, NIH CTSA program grant UM1TR004403, NIH NHLBI R01HL169765, NIH NHLBI R01HL126771/NH/NIH HHS/United States ; COVID-19 and Emerging Respiratory Viruses Research Award//American Lung Association/ ; },
abstract = {Post-acute sequelae of COVID-19 (Long COVID) includes physical and cognitive symptoms that can last long after acute infection. Links between lung pathophysiology and cognitive dysfunction in Long COVID remain largely unexplored. Long COVID participants were recruited from a post-COVID-19 clinic. Participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) symptom questionnaires for Sleep Disturbance, Anxiety, Depression, and Cognitive Function, the National Institute of Health Toolbox Cognition Battery (NIHTB-CB), pulmonary function tests (spirometry, diffusion capacity of the lung), structural and functional brain magnetic resonance imaging (MRI), and [129]Xe MRI for ventilation and regional pulmonary gas exchange evaluation, at the same study visit. Bivariate relationships between lung and cognitive function in Long COVID were assessed using Spearman partial correlations, adjusted for age. Twelve participants (age = 54 ± 11 yrs.; 10 females) that were 32 ± 5 months from infection were evaluated. PROMIS symptom scores indicated reduced perceived cognitive function in everyday life along with increased fatigue, anxiety, depressive symptoms, and sleep disturbance. However, objective cognitive function performance on NIHTB-CB were broadly within normal limits. Lower [129]Xe MRI gas exchange was correlated with more severe symptoms of sleep disturbance, reduced executive functioning performance, and elevated cerebral perfusion via brain MRI. These results are suggestive of a link between lung pathophysiology and cognitive dysfunction in this Long COVID population with enduring respiratory and cognitive symptoms more than two years after infection.},
}

@article {pmid41285857,
year = {2025},
author = {Green, R and Marjenberg, Z and Lip, GYH and Banerjee, A and Wisnivesky, J and Delaney, BC and Peluso, MJ and Wynberg, E and Abduljawad, S},
title = {A systematic review and meta-analysis of the impact of vaccination on prevention of long COVID.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {10326},
pmid = {41285857},
issn = {2041-1723},
abstract = {Long COVID affects millions worldwide and its prevention is a critical public health strategy. While prior analyses show primary vaccination prevents long COVID in subsequent infections, the effect of booster vaccination on long COVID after Omicron infections is unclear. This systematic review identifies 31 observational studies, of which 11 are suitable for pairwise meta-analyses. The pooled odds ratio (OR) of long COVID in those vaccinated (any dose) versus unvaccinated is 0.77 (95% confidence interval [CI] 0.70-0.85; p < 0.0001; 10 studies). ORs were also lower for primary course vaccination versus unvaccinated (OR 0.81; 95% CI 0.79-0.83; p < 0.0001; 3 studies), booster vaccination versus unvaccinated (OR 0.74; 95% CI 0.63-0.86; p = 0.0001; 4 studies), and booster vaccination versus primary course vaccination (OR 77; 95% CI 0.65-0.92; p = 0.0044; 3 studies). These findings indicate that booster vaccination can provide additional protection against long COVID, highlighting the importance of seasonal vaccination against new SARS-CoV-2 variants. They should, however, be interpreted cautiously, given the small number of studies and the low quality of evidence.},
}

@article {pmid41285594,
year = {2025},
author = {Lubell, J},
title = {To Ground Research in the Lived Experience of Patients and Caregivers, Give Us a Voice!.},
journal = {Annals of family medicine},
volume = {23},
number = {6},
pages = {570-572},
doi = {10.1370/afm.240494},
pmid = {41285594},
issn = {1544-1717},
mesh = {Humans ; *Caregivers/psychology ; Female ; *Biomedical Research ; Fatigue Syndrome, Chronic/therapy/psychology ; },
abstract = {My daughter has been diagnosed with a range of chronic conditions, including Hyper-mobile Ehlers-Danlos Syndrome and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). I have approached my role as caregiver in the same way I approach my day job leading social science research: reading the literature, carefully observing her condition, and developing hypotheses about her conditions and how they might be treated. I now have more than 7 years of longitudinal observation-a wealth of data-but no easy way to share with the medical research community the hypotheses these observations have engendered and my ideas about how to productively structure future research to accelerate progress toward treatments for her and others like her. In this essay, I share my thoughts on why patient and caregiver observations and hypotheses are important and how the medical research field might tap into them to make faster progress toward effective treatments for complex medical conditions.},
}

Humans
*Caregivers/psychology
Female
*Biomedical Research
Fatigue Syndrome, Chronic/therapy/psychology

@article {pmid41283027,
year = {2025},
author = {Cousins, O and Jokela-Pansini, M and Alwan, NA and Barnard, E and Dainow, J and Dalton, C and Davies, G and Faghy, MA and Gilmour, E and Patel, I and Sherwood, O and Westerhof, L and Greenhough, B},
title = {Co-creating a social science research agenda for Long Covid.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1654488},
pmid = {41283027},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/therapy ; *Social Sciences ; Surveys and Questionnaires ; Female ; Male ; *Research ; SARS-CoV-2 ; Adult ; Middle Aged ; Health Personnel ; },
abstract = {INTRODUCTION: Our objective was to understand how social scientific research could best address the needs and concerns of patients, families, carers, healthcare professionals, academics, private and public sector professionals, and volunteers from Long Covid charities and support groups and people with lived experience of Long Covid. We worked with different stakeholders to develop a list of research priorities that particularly focused on social science as this is where our collective expertise lies, but similar methods could also be used to set research priorities in the natural sciences, medicine or the humanities.

METHODS: We used purposive sampling and conducted two online surveys. The first online survey (N = 57) asked participants to identify their top five questions of concern, which resulted in a list of 253 questions. These questions were then consolidated, refined and edited down to 55 questions, categorized by topic. In the second survey (N = 66), we asked participants to select and rank their top 10 questions from this refined list. The final output was a ranked list of nine questions based on those prioritized by at least 50% of the respondents.

RESULTS: Nine research questions were developed concerning (i) treatments, therapies, and strategies; (ii) financial support; (iii) repeated reinfections; (iv) training of healthcare professionals; (v) mental health impact; (vi) future of research funding; (vii) airborne transmissions of COVID-19; (viii) developing therapeutics informed by patients' experiences; and (ix) socioeconomic impacts of Long Covid. Many of the issues raised mirror those discussed in previous work in the UK and internationally, but additional novel themes emerged, underscoring the value of this collaborative approach.

CONCLUSION: Our survey revealed the value of including the voices of diverse individuals affected by Long Covid and those working in this area and highlighted priorities for social science in the field of Long Covid research.},
}

Humans
*COVID-19/therapy
*Social Sciences
Surveys and Questionnaires
Female
Male
*Research
SARS-CoV-2
Adult
Middle Aged
Health Personnel

@article {pmid41282857,
year = {2025},
author = {Dunckley, N and Zhang, N and Adler, CH and Shill, HA and Mehta, S and Driver-Dunckley, E and Belden, CM and Atri, A and Choudhury, P and Kuramoto, A and Serrano, GE and Beach, TG},
title = {Post-Acute COVID-19 Effects on Diagnostic Conversion Rates And Standardized Cognitive and Motor Test Scores in a Longitudinal Study of Independent, Community-Recruited Elderly Subjects.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.20.25338408},
pmid = {41282857},
abstract = {There is considerable concern about the long-term consequences of COVID-19 infection, generally referred to as post-acute sequelae, including declines in cognitive and motor abilities. The degree to which COVID-19 contributes additional burden to normal aging trajectories remains unclear. Additionally, the impact of COVID-19 on subjects under study for age-related neurological diseases is a potential confounder that needs definition. This study investigated whether having had a COVID-19 illness was associated with a differential decline in cognitive or motor function in older adults, utilizing data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and Brain and Body Donation Program (BBDP), a longitudinal clinicopathological study based in metropolitan Phoenix, Arizona. Subjects were included if they 1) had completed a questionnaire about their experience with COVID-19 illness 2) were classified as cognitively normal at pre-pandemic diagnostic cognitive consensus conferences and 3) had one or more subsequent diagnostic conferences between July 1, 2020 and August 30, 2025. All subjects had serial standardized research-dedicated clinical evaluations including the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale (UPDRS). Specific objectives were to compare, between those who reported having had or not having had COVID-19, rates of conversion to cognitive impairment or dementia as well as pre-pandemic and final MoCA and UPDRS motor scores. A total of 100 subjects self-reported having had COVID-19 while 71 denied having had it. Their related acute illness severity was generally mild, with only 10% having had hospital treatment and none having required ventilator support. Post-acute symptoms were also mild; only 1 subject reported having "long Covid". Both cognitive and motor performance, as measured by MoCA and UPDRS part 3 scores, declined slightly (not statistically significant) over the study period. Conversion of cognitive diagnosis from normal to impaired or dementia occurred in 26% of those having had COVID-19 and in 32% of those not having had COVID-19; the difference was not significant. All subjects diagnosed with PD at the start of the study were also diagnosed with PD at the end of the study; no subjects converted from not having to having probable PD. Logistic regression analysis indicated that subjects' report of having had COVID-19 was not significantly associated with conversion to cognitive impairment or dementia while greater age, male sex, possession of one or more apolipoprotein E-ε4 alleles, and a diagnosis of probable PD all conferred a significantly greater likelihood of conversion. The results suggest that having a mild COVID-19 illness is not associated with greater declines on cognitive or motor screening tests than would be expected from age-related changes alone. Limitations of this analysis include small sample sizes, potential misclassification of COVID-19 status, and reliance on relatively crude clinical metrics that may miss significant functional changes. Additionally, we were unable to separately assess for varying COVID-19 severity dependent on whether or not the subject had been vaccinated, the number and type of vaccinations, and the particular SARS-CoV-2 variants that were circulating at the time of illness.},
}

@article {pmid41282756,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, MM and Gebo, K and Nash, D and , },
title = {Long COVID Longitudinal Symptoms Burden Clusters Within A National Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.01.25339283},
pmid = {41282756},
abstract = {BACKGROUND: Long COVID is clinically heterogeneous, with evolving symptom trajectories that complicate classification. Prior clustering studies often rely on Electronic Health Records data, risking underreporting. We used longitudinal, community-based data to characterize symptom clusters and risk factors.

METHODS: We analyzed CHASING COVID Cohort participants with confirmed SARS-CoV-2 infection between December 2020 and December 2022, ≥12 months of follow-up, and long COVID (≥1 new symptom and concurrent activity limitation 3-12 months post-infection, both absent pre-infection). The infection in this window was the index infection; those with pre-index long COVID were excluded. Symptoms were self-reported pre-infection and at ∼3, 6, 9, and 12 months. Missing data were handled via multiple imputation by chained equations (30 datasets). Longitudinal K-means clustering was performed within each imputed dataset, with hierarchical aggregation to derive final assignments. Multivariable logistic regression (adjusting for age, sex) assessed associations of demographic, clinical, and social factors with cluster membership. Within the highest-burden cluster, hierarchical clustering identified symptom phenotypes.

RESULTS: Of 1,787 infected participants, 511 met criteria (22% ≥50 years; 55% female; 60% White non-Hispanic; 54% mental health disorder; 7.2% immunodeficiency; 21% ≥2 comorbidities; 30% prior infection; 24% never vaccinated pre-index). Three clusters emerged: highest, moderate, and lowest burden. The highest-burden cluster (median 6 symptoms at 6 and 9 months) was characterized by fatigue (57%-74%), concentration difficulty, post-exertional malaise, myalgia, sleep disturbance, gastrointestinal symptoms, headache, irritability, and mobility limitations (each ∼46%-53%). The moderate cluster peaked at 3 symptoms (fatigue 42%); the lowest remained ∼1 symptom (fatigue 24% at 12 months). Older age (aOR 2.68, 95% CI 1.59-4.53), female sex (2.36, 1.48-3.76), mental health disorder (2.65, 1.65-4.25), and immunodeficiency (4.23, 1.71-10.51) were associated with highest vs lowest burden. Within the highest-burden cluster, three phenotypes emerged: neurological/multisystemic, psychiatric/neurological, and physical/respiratory.

CONCLUSIONS: Distinct long-COVID clusters and phenotypes underscore heterogeneity and support tailored management and risk stratification.},
}

@article {pmid41282714,
year = {2025},
author = {Pearson, ML and Laraway, BJ and Elias, ER and Bilousova, G and Haendel, MA and , },
title = {Understanding Comorbidities in Hypermobile Ehlers-Danlos Syndrome: Could a Viral Infection Lead to a Diagnosis?.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.22.25338573},
pmid = {41282714},
abstract = {UNLABELLED: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a complex, underdiagnosed connective tissue disorder characterized by widespread symptoms affecting multiple organ systems. Recent clinical observations suggest that individuals with hEDS may be at increased risk for persistent symptoms following COVID-19, commonly referred to as Long COVID. Using data from over 23 million patients across the United States, we examined associations between hEDS, COVID-19 infection, Long COVID, and related chronic conditions. We identified nearly 30,000 individuals with hEDS and found that the estimated prevalence was approximately 1 in 800, higher than previously recognized. While rates of COVID-19 infection were similar between patients with hEDS and matched controls, those with hEDS were significantly more likely to develop Long COVID. This risk was especially elevated among patients with hEDS with overlapping conditions commonly seen in post-viral syndromes, including autonomic dysfunction, immune dysregulation, and chronic fatigue. Specifically, individuals with postural orthostatic tachycardia, mast cell-related symptoms, or chronic fatigue syndrome had the highest rates of Long COVID. Cumulative incidence analysis revealed that many patients received an hEDS diagnosis only after a COVID-19 infection, suggesting that viral illness may exacerbate or reveal previously unrecognized symptoms. Patients with hEDS also exhibited higher odds of having additional risk factors for severe or prolonged illness, including chronic lung and autoimmune conditions, depression, and cerebrovascular disease. These findings highlight a previously unrecognized vulnerability in patients with hEDS and underscore the need for greater clinical awareness of their heightened risk for persistent post-COVID illness. Improved screening, earlier diagnosis, and integrated care pathways are urgently needed to support this complex and underserved patient population.

AUTHOR SUMMARY: We studied patients with hypermobile Ehlers-Danlos Syndrome (hEDS), a connective tissue condition that affects joints, skin, and many body systems. This condition is often misunderstood or overlooked, leaving many people undiagnosed. During the COVID-19 pandemic, people with hEDS appeared to experience more long-term symptoms after infection, a condition often called Long COVID. Here, we analyzed the health records of millions of patients in the United States to better understand post-viral outcomes.Patients with hEDS were more likely to be diagnosed with Long COVID compared to similar patients without hEDS. This was especially true for those who also had conditions such as chronic fatigue, immune conditions, or issues with heart rate and blood pressure regulation. In many cases, people were diagnosed with hEDS for the first time only after they had COVID-19, suggesting the virus may worsen or reveal symptoms that had been previously missed.Our findings show that hEDS may be more common than previously thought and that such patients face higher risks after COVID-19. Greater awareness and earlier recognition of hEDS could improve care for many patients with complex, long-lasting symptoms.},
}

@article {pmid41282703,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, M and Gebo, K and Nash, D},
title = {Effect of a Third COVID-19 Vaccine Dose on the Incidence of Long COVID Among Adults Who Completed a Primary Vaccine Series: a Target Trial Emulation in a Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.03.25339444},
pmid = {41282703},
abstract = {BACKGROUND: Evidence on whether a third COVID-19 vaccine dose lowers long COVID risk is mixed. We estimated the effect of receiving >=1 third dose versus completing only a primary series on 6 and 12 month long COVID incidence using a target trial emulation in a U.S. community cohort.

METHODS: We analyzed the CHASING COVID Cohort, a prospective, community based study of U.S. adults. Eligible participants were >=18 years, had completed a two dose primary series, had no prior long COVID, and had no SARS-CoV-2 infection in the 3 months before time zero. Strategies compared were: receive a third dose at time zero vs. not receive a third dose during follow up. Long COVID was defined as >=1 new symptom at or beyond 3 months post infection with concurrent activity limitation, both absent in the prior year. Follow up was 6 and 12 months. We used a per protocol analog: participants were artificially censored upon deviating from their assigned strategy or lost to follow up, with inverse probability weights to address selection due to censoring and time varying confounding. We fit weighted pooled logistic models to estimate weighted incidence, differences, and ratios at each horizon.

RESULTS: Across 16 sequential trials (18,930 person trials; 4,044 unique individuals), 3,321 person trials received a third dose at time zero and 15,609 did not. At 6 months, weighted long COVID incidence was 0.9% (95% CI, 0.5%, 1.3%) with a third dose vs. 1.0% (0.8%, 1.1%) without (risk difference (RD), -0.1%; 95% CI, -0.5%, 0.4%; risk ratio (RR), 0.93; 95% CI, 0.54, 1.44). At 12 months, incidence was 4.9% (4.1%, 5.9%) with a third dose vs. 4.5% (4.1%, 4.8%) without (RD, 0.4%; 95% CI, -0.5%, 1.4%; RR, 1.09; 95% CI, 0.90, 1.33).

CONCLUSION: In this community based target trial emulation, receiving a third COVID-19 vaccine dose did not meaningfully reduce 6 or 12 month long COVID incidence compared with completing only a primary series.},
}

@article {pmid41282682,
year = {2025},
author = {Shen, Y and Shahn, Z and Robertson, M and Gebo, K and Nash, D},
title = {Natural History of Self-reported Symptoms Following SARS-CoV-2 Infection: A Target Trial Emulation in a Prospective Community-Based Cohort.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.01.25339316},
pmid = {41282682},
abstract = {BACKGROUND: The natural history of symptoms after SARS-CoV-2 infection remains uncertain because many studies are not representative, ignore background symptom prevalence, lack longitudinal tracking, and omit appropriate controls. Using a prospective, community-based cohort with repeated symptom measures, we estimated post infection risks of long COVID symptoms versus contemporaneous uninfected controls.

METHODS: We analyzed the CHASING COVID Cohort, a U.S. longitudinal study with surveys and serology (March 2020 to December 2023). Infection status (January 2021 to December 2022) was determined from self-reported PCR/antigen results, serology, or CSTE probable criteria. We emulated 24 monthly target trials comparing individuals newly infected at time zero with those remaining uninfected. Outcomes were new onset long COVID symptoms not reported pre-infection, assessed overall and within three clusters (neurological, autonomic, exercise intolerance) at 4 to 8 and 9 to 12 months post infection. Inverse probability of treatment and censoring weights adjusted for confounding and informative loss to follow up.

RESULTS: The analysis included 1,055 infected and 52,310 uninfected person-trials. At 4 to 8 months, the adjusted risk of any long-COVID symptom was 22.6% (95% CI 20.5, 24.8) among infected versus 11.3% (11.1, 11.5) among uninfected (adjusted risk difference [aRD], 11.3% [9.2, 13.5]; adjusted risk ratio [aRR], 2.01 [1.81, 2.20]). At 9 to 12 months, risks were 19.2% (17.0, 21.3) vs 12.4% (12.2, 12.7) (aRD, 6.7% [4.6, 8.9]; aRR, 1.54 [1.37, 1.72]). Across all three clusters, infected participants had consistently higher risks at both intervals.

CONCLUSIONS: SARS-CoV-2 infection was associated with elevated risk of new-onset long-COVID symptoms persisting up to 12 months. Using a national community based cohort, contemporaneous uninfected controls, and target trial emulation clarifies the burden attributable to infection and supports ongoing surveillance and targeted prevention and care.},
}

@article {pmid41282213,
year = {2025},
author = {Staab, KR and McIntosh, MJ and Puliyakote, ASK and Hahn, AD and Alarab, N and Percy, JL and Lanning, T and Theeler, J and Linkenmeyer, C and Wharff, CJ and Bruening, E and Sieren, JC and Hoffman, EA and Comellas, AP and Hoth, KF and Fain, SB},
title = {Long COVID: Lung Pathophysiology and its Relationship with Cognitive Dysfunction.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7464124/v1},
pmid = {41282213},
issn = {2693-5015},
abstract = {Post-acute sequelae of COVID-19 (Long COVID) includes physical and cognitive symptoms that can last long after acute infection. Links between lung pathophysiology and cognitive dysfunction in Long COVID remain largely unexplored. Long COVID participants were recruited from a post-COVID-19 clinic. Participants completed Patient-Reported Outcomes Measurement Information System (PROMIS) symptom questionnaires for Sleep Disturbance, Anxiety, Depression, and Cognitive Function, the National Institute of Health Toolbox Cognition Battery (NIHTB-CB), pulmonary function tests (spirometry, diffusion capacity of the lung), structural and functional brain magnetic resonance imaging (MRI), and 129 Xe MRI for ventilation and regional pulmonary gas exchange evaluation, at the same study visit. Bivariate relationships between lung and cognitive function in Long COVID were assessed using Spearman partial correlations, adjusted for age. Twelve participants (age=54±11 yrs.; 10 females) that were 32±5 months from infection were evaluated. PROMIS symptom scores indicated reduced perceived cognitive function in everyday life along with increased fatigue, anxiety, depressive symptoms, and sleep disturbance. However, objective cognitive function performance on NIHTB-CB were broadly within normal limits. Lower 129 Xe MRI gas exchange was correlated with more severe symptoms of sleep disturbance, reduced executive functioning performance, and elevated cerebral perfusion via brain MRI. These results are suggestive of a link between lung pathophysiology and cognitive dysfunction in this Long COVID population with enduring respiratory and cognitive symptoms more than two years after infection.},
}

@article {pmid41282195,
year = {2025},
author = {Dominguez, JC and Fowler, KC and Koralnik, IJ and Liow, K and Ampil, E and Zhi, Q and Laxamana, L and Berroya, R and Noris, CJ and Meropol, SB and Troxel, AB},
title = {Analysis of the National Institutes of Health COVID-19 Neuro Databank by geographic region and income status.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7371770/v1},
pmid = {41282195},
issn = {2693-5015},
abstract = {Background While COVID-19 is more commonly known to present and persist in terms of respiratory symptoms, evidence for neurologic manifestations is limited. Objectives This study aims to provide an epidemiological overview of neurologic manifestations of COVID-19. It compares the demographic and clinical profiles of patients based on geographic location and country income classification. Moreover, it describes the neurologic manifestations of Long COVID. Methods This was a cross-sectional analysis of a multi-country cohort of patients with COVID-19-associated neurologic symptoms enrolled in the COVID-19 Neuro Databank from January 2020 to February 2025. Demographic, clinical and health system-related factors were described. Comparisons among geographic regions and income classifications were performed via analysis of variance and chi-square tests or Fisher's exact tests. Results Majority of the 3,901 patients were from the United States (U.S.) and from high-income countries. The mean age was 57.27±18 years and 54% were males. Neurologic comorbidities were highest in the U.S. whereas non-neurologic comorbidities. Asia had the greatest frequency of severe COVID and mortality. Vaccination and use of COVID-19 medication was lowest in Africa. There were significant associations between COVID-19 vaccination and use of COVID-19 medications with income level. The five leading COVID-19-associated neurologic conditions were neurocognitive disorders, fatigue, headache, anosmia, and ageusia. A subset of Long COVID was identified as thought disorders, fatigue, mood disorders, stroke, headache, and neurocognitive disorders. Conclusions This study provides insight into the varying profile and burdens of COVID-19 associated neurologic conditions and the health inequities during the pandemic among geographic and income groups.},
}

@article {pmid41280901,
year = {2025},
author = {Fricke, F and Mai, F and Wossidlo, C and Steinbeck, F and Bergmann-Ewert, W and Kordt, M and Kraft, K and Müller, B and Reisinger, EC and Müller-Hilke, B},
title = {Transcriptome analysis of classical blood cells reveals downregulation of pro-inflammatory genes in the classical monocytes of long COVID patients.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1710783},
pmid = {41280901},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/genetics/blood ; *Monocytes/immunology/metabolism ; Male ; Female ; Gene Expression Profiling ; *SARS-CoV-2/immunology ; Middle Aged ; Down-Regulation ; Adult ; *Transcriptome ; Inflammation/genetics/immunology ; Single-Cell Analysis ; Cytokines/blood ; Aged ; Leukocytes, Mononuclear/immunology ; },
abstract = {INTRODUCTION: Despite extensive research, the pathogenesis and predispositions underlying long COVID (long-term coronavirus disease 2019) remain poorly understood.

METHODS: To address this, we analyzed the immunological landscapes of 44 patients with long COVID and 44 matched convalescents using single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and validated the findings with plasma cytokine measurements via Luminex technology.

RESULTS: While the immune cell compositions showed minimal quantitative differences only among natural killer (NK) cells, the transcriptome analyses identified distinct gene expression patterns, particularly in classical monocytes: patients with long COVID exhibited downregulation of the inflammation-associated genes, including IL1B and CXCL2. Imputation of the transcription factor activity hinted at a reduced inflammasome activity (via SNAI1) and an impaired monocyte differentiation (via ATF2) in long COVID. The RNA velocity data supported the presence of immature classical monocytes in these patients.

DISCUSSION: These findings show that monocytes might be dysregulated and/or exhausted in patients with long COVID.},
}

Humans
*COVID-19/immunology/genetics/blood
*Monocytes/immunology/metabolism
Male
Female
Gene Expression Profiling
*SARS-CoV-2/immunology
Middle Aged
Down-Regulation
Adult
*Transcriptome
Inflammation/genetics/immunology
Single-Cell Analysis
Cytokines/blood
Aged
Leukocytes, Mononuclear/immunology

@article {pmid41280592,
year = {2025},
author = {},
title = {Erratum: An audit of 12 cases of long COVID following the Lightning Process intervention examining benefits and harms.},
journal = {Journal of family medicine and primary care},
volume = {14},
number = {10},
pages = {4407},
pmid = {41280592},
issn = {2249-4863},
abstract = {[This corrects the article on p. 796 in vol. 14, PMID: 40115575.].},
}

@article {pmid41279626,
year = {2025},
author = {Liu, JA and Chaulagain, S and Creisher, PS and Zhong, W and Zhang, T and Taddese, M and Shi, K and Park, HS and Hcnir, H and Arnold, AP and Baric, RS and Barahona, NB and Engler-Chiurazzi, EB and Zwezdaryk, KJ and Thio, CL and Balagopal, A and Harkema, JR and Thompson, EA and Pekosz, A and Cox, AL and Klein, SL},
title = {Mechanisms of sex differences in acute and long COVID sequelae in mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.13.682101},
pmid = {41279626},
issn = {2692-8205},
abstract = {While males are more likely to suffer severe outcomes during acute COVID-19, a greater proportion of females develop post-acute sequalae of COVID-19 (PASC) despite similar rates of infection. To identify mechanisms of PASC, mice were infected with SARS-CoV-2 and viral, inflammatory, and behavioral outcomes were evaluated through 84 days post infection. Sex differences were not observed in virus replication or persistence of viral RNA in pulmonary or extrapulmonary tissues in acute or PASC phases. Following recovery from infection, female mice exhibited persistent neurocognitive and behavioral impairments, along with greater frequencies of inflammatory myeloid subsets, neuroinflammation, and dysregulated T cell subsets, including Tregs. Sex differences in inflammation and cognitive phenotypes during PASC were mediated by the presence of two X chromosomes. XX animals independent of chromosome Y presented with neuroinflammation and PASC along with infection-induced upregulation of the X-linked genes Xist and Tlr7 that regulate inflammation and chronic disease outcomes.},
}

@article {pmid41278460,
year = {2025},
author = {Zheng, T and Gao, R and Liu, Y and Wang, Y and Wu, C and Guo, L and Chen, L and Wang, X and Xiao, Y and Zhong, J and Zhang, R and Wang, Y and Ren, X and Cao, B and Ren, L and Wang, J},
title = {T cell-driven sustained inflammation and immune dysregulation mimicking immunosenescence for up to three years post-COVID-19.},
journal = {Immunity & inflammation},
volume = {1},
number = {1},
pages = {11},
pmid = {41278460},
issn = {3059-4774},
abstract = {UNLABELLED: Long COVID has emerged as a major global health concern, yet the long-term trajectory of immune recovery and its contribution to persistent symptoms remain to be elucidated. Here, we conducted a three-year longitudinal follow-up of the 47 COVID-19 patients and applied single-cell RNA sequencing (scRNA-seq) and multiplex cytokine profiling to comprehensively characterize the peripheral immune landscape during convalescence. We observed persistent immune dysregulation up to three years post-infection, characterized by chronic inflammation and impaired restoration of naïve CD4[+] T cells, naïve CD8[+] T cells, and SLC4A10[+] MAIT cells-features reminiscent of immunosenescence. Notably, Th17 cells, rather than monocytes, emerged as key drivers of chronic inflammation beyond one year. We identified two distinct Th17 subsets: RORC[+] Th17 cells and LTB[+] Th17 cells. While RORC[+] Th17 cells were negatively correlated with inflammatory cytokine levels, LTB[+] Th17 cells showed proinflammatory features and were positively associated with long COVID symptoms. Sustained elevation of S100A8 and IL-16 in follow-up patients may contribute to the persistent presence of LTB[+] Th17 cells. Together, our study provides an in-depth longitudinal map of immune remodeling in COVID-19 convalescents, revealing key cellular and molecular drivers of sustained inflammation up to three years post-infection.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44466-025-00012-2.},
}

@article {pmid41277895,
year = {2025},
author = {Cabello Fernandez, C and Didone, V and Lesoinne, A and Slama, H and Fery, P and Rousseau, AF and Moutschen, M and , and Collette, F and Willems, S},
title = {Cognitive and affective psychoeducation for Long COVID: a randomized controlled trial.},
journal = {Brain communications},
volume = {7},
number = {6},
pages = {fcaf447},
pmid = {41277895},
issn = {2632-1297},
abstract = {Long COVID is a complex condition characterized by persistent symptoms, including cognitive difficulties and fatigue, which significantly impact daily functioning. Although various intervention strategies inspired by approaches used in the rehabilitation of other neurological conditions have been developed to address these issues, evidence of their efficacy in Long COVID populations remains limited. This study aimed to compare the effectiveness for cognitive complaints of two psychoeducational interventions-one focused on cognitive difficulties and the other on affective symptoms in Long COVID patients with cognitive problems. COVCOG (Long COVID: treatment of cognitive difficulties) is a randomized controlled trial using a parallel two-group design. Long COVID patients underwent neuropsychological assessments at pre-, 2- and 8-month post-intervention. The intervention comprised four 90-min sessions of either a cognitive-focused or an affective-focused psychoeducational programme. The effects were measured on cognitive complaints (primary outcome), cognitive performance, fatigue, sleep difficulties, quality of life, psychological distress, and impact on work and daily activities (secondary outcomes). Linear mixed models (LMMs) were used. One hundred and thirty Long COVID patients were randomized. One hundred and twenty-two (mean age: 47 ± 10; 69.7% female) were included (63 in the cognitive group and 59 in the affective group). The low dropout rate (12% at 2 months and 9% at 8 months post-intervention) and the patients' substantial active engagement-92% attended all intervention sessions-assured the feasibility of both interventions. LMM analysis revealed a statistically significant improvement with time in subjective cognitive complaints, objective cognitive performance (attention, working memory and long-term memory), quality of life, fatigue, sleep, some psychological distress subscales and work impairment (all Ps < 0.03, with small to moderate effect sizes), but no group-by-time interaction, suggesting that trajectories did not differ between arms. However, some improvements are specific to one intervention or the other. Designed specifically for this population, both psychoeducative interventions provide insights into improving the management of Long COVID patients with cognitive problems. Longer treatment may be needed for more meaningful improvements. Clinicaltrials.gov: NCT05167266.},
}

@article {pmid41277355,
year = {2025},
author = {Foscolou, A and Pratti, T and Detopoulou, P and Argyri, K and Nikolaou, G and Kouskouti, A and Malikourti, A and Petrogianni, M and Shurdha, E and Psaroudaki, E and Panoutsopoulos, GI and Vamvakas, S and Gioxari, A},
title = {Dietary n-3 Polyunsaturated Fatty Acids From Fish Are Associated With Better Healthy Aging Indicators: Results of the DIAPELH Study.},
journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association},
volume = {38},
number = {6},
pages = {e70169},
doi = {10.1111/jhn.70169},
pmid = {41277355},
issn = {1365-277X},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Fatty Acids, Omega-3/administration & dosage ; Aged ; Male ; Female ; Cross-Sectional Studies ; *Healthy Aging/physiology ; Greece/epidemiology ; Middle Aged ; *Fishes ; Animals ; Diet, Mediterranean/statistics & numerical data ; *Seafood ; COVID-19/epidemiology ; *Diet ; Cognition ; Aged, 80 and over ; Depression/prevention & control ; SARS-CoV-2 ; Aging ; },
abstract = {INTRODUCTION: Promoting healthy aging is a public health goal, especially in regions with a high proportion of older adults, such as Greece. This cross-sectional study investigated the association of fish n-3 PUFA intake with indicators of healthy aging among older Greek Peloponnesian adults.

METHODS: In total, 449 individuals > 60 years of age were enroled. Sociodemographic, anthropometrical, medical, mobility, balance, lifestyle, dietary, cognitive and mental characteristics were assessed through validated questionnaires and procedures.

RESULTS: Analyses revealed that n-3 PUFA intake was associated with fewer depression symptoms (p < 0.001), higher cognition levels (p = 0.012) and levels of healthy aging (p < 0.001), derived from Successful Aging Index (SAI). In parallel, n-3 PUFA intake was associated with higher adherence to the Mediterranean diet (p < 0.001). Additionally, n-3 PUFA intake was inversely correlated with the presence of long COVID-19 symptomatology (p = 0.036). No association of n-3 PUFA intake with mobility or physical performance and balance (all ps> 0.05) was detected.

CONCLUSION: The results underscore the significance of nutrition in older adults, highlighting the possible protective impact of n-3 PUFAs on maintaining functionality. Future prospective studies may validate these associations and contribute to the development of targeted nutritional strategies for older adults.},
}

Humans
*Fatty Acids, Omega-3/administration & dosage
Aged
Male
Female
Cross-Sectional Studies
*Healthy Aging/physiology
Greece/epidemiology
Middle Aged
*Fishes
Animals
Diet, Mediterranean/statistics & numerical data
*Seafood
COVID-19/epidemiology
*Diet
Cognition
Aged, 80 and over
Depression/prevention & control
SARS-CoV-2
Aging

@article {pmid41277094,
year = {2025},
author = {Mustonen, T and Kytölä, P and Lantto, H and Lager, E and Vangelova-Korpinen, V and Virrantaus, H and Sulg, A and Stålnacke, S and Posharina, T and Luukkonen, R and Uusitalo, A and Piirilä, P and Kanerva, M},
title = {Characterization of sympathicotonia in post-covid condition (long covid) and healthy controls using long-term electrodermal activity (EDA) follow-up.},
journal = {Clinical physiology and functional imaging},
volume = {45},
number = {6},
pages = {e70037},
doi = {10.1111/cpf.70037},
pmid = {41277094},
issn = {1475-097X},
support = {101057553//European Union's Horizon Europe research and innovation/ ; Y780022061//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; Y780024073//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; Y780023041//Helsinki University Central Hospital Research Funding for HUS Medical Diagnostic Center/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/complications/physiopathology/diagnosis ; Middle Aged ; *Galvanic Skin Response ; Adult ; *Sympathetic Nervous System/physiopathology ; Case-Control Studies ; Time Factors ; Aged ; Post-Acute COVID-19 Syndrome ; Follow-Up Studies ; },
abstract = {PURPOSE: After SARS-CoV-2 infection, some patients develop post-COVID condition (PCC), often associated with sympathicotonia. This study aimed to characterize sympathicotonia in PCC patients using a novel long-term electrodermal activity (EDA) analysis via a smart ring and evaluate its clinical applicability.

METHODS: Seventeen PCC patients were recruited from a Long Covid outpatient clinic, and 18 healthy controls volunteered. PCC patients were divided based on self-reported symptoms into those with or without sympathicotonia. A 14-day EDA monitoring was conducted. Sympathetic nervous system (SNS) activity was expressed as a double normalized index of electrodermal activity (DNE), with higher levels indicating higher SNS activity. Orthostatic tests were performed to identify orthostatic sympathicotonia. DNE levels, representing EDA, were compared to self-reported and orthostatic sympathicotonia.

RESULTS: DNE levels did not differ between PCC patients with (N = 12) or without (N = 5) self-reported sympathicotonia or compared with nonsympathetic controls. When dividing all participants by orthostatic test results, DNE levels were lower during day (08:00-14:00; p < 0.05) but higher during late night (00:00-02:00; p < 0.05) in those with orthostatic sympathicotonia (N = 21) compared to those without (N = 14), with the 24-h comparison significant (p = 0.022). Among PCC patients, DNE levels were higher in orthostatic nonsympathicotonic (N = 7) than orthostatic sympathicotonic (N = 10) during morning (09:00-12:00; p < 0.05), with the 24-h comparison significant (p = 0.044).

CONCLUSION: Self-reported symptoms did not distinguish sympathicotonia. However, individuals with orthostatic test-identified sympathicotonia had heightened EDA, indicating increased sympathetic activity, particularly during late night. PCC was not identifiable by EDA. Long-term EDA monitoring may provide an objective tool for detecting sympathicotonia independently of self-reported symptoms.},
}

Humans
Male
Female
*COVID-19/complications/physiopathology/diagnosis
Middle Aged
*Galvanic Skin Response
Adult
*Sympathetic Nervous System/physiopathology
Case-Control Studies
Time Factors
Aged
Post-Acute COVID-19 Syndrome
Follow-Up Studies

@article {pmid41274384,
year = {2025},
author = {Schmitz, B and Garbsch, R and Schäfer, H and Bär, C and Chatterjee, S and Riemekasten, G and Schulze-Forster, K and Heidecke, H and Schultheiß, C and Binder, M and Mooren, FC},
title = {Autonomic dysfunction and vasoregulation in Long COVID-19 are linked to anti-GPCR autoantibodies.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2025.10.034},
pmid = {41274384},
issn = {1097-6825},
abstract = {BACKGROUND: SARS-CoV-2-triggered autoantibodies (AAB) targeting G protein-coupled receptors (GPCRs) have been suggested to contribute to the post-acute sequelae of COVID-19 (Post-COVID-19 Syndrome, PCS).

OBJECTIVE: To characterize AABs involved in autonomic dysfunction such as rhythm control and vasoregulation in patients with post-acute sequelae of COVID-19 and profile the peripheral B- and T-cell receptor (B/TCR) architecture to identify immunogenetic imprints of autoimmunity.

METHODS: Anti-GPCR AABs were characterized in patients with post-acute sequelae of COVID-19 with known alteration in autonomic nervous system functions assessed by heart rate variability (HRV). Adaptive immune receptor repertoire sequencing (AIRR-seq) was used to profile peripheral BCR and TCR architecture. COVID-19 patients with severe or moderate acute disease, after recovery, and pre-pandemic healthy individuals served as controls. Cardio- and vasoactive effects of AABs were analyzed using 24h and exercise test blood pressure measurements. The direct effect of AABs on electromechanical coupling was tested in human induced pluripotent stem cell cardiomyocytes.

RESULTS: AABs including AGT1/2Rab, ADRB1/2ab, M1/3Rab, and CXCR3ab were associated with HRV alterations. Analysis of the broad BCR repertoire metrics revealed high similarity between PCS patients and healthy controls for clonality and diversity measures. The level of somatic hypermutation as proxy for antigen-experience was equal to healthy controls. Elevated CXCR3ab levels were linked to higher 24h mean arterial pressure, while patients with elevated M1Rab and CXCR3ab levels showed higher blood pressure during stress tests. AABs had no effect on beat frequence and amplitude of cardiomyocyte contraction in vitro.

CONCLUSIONS: These findings suggest that AABs play a modulatory role in sympathetic nervous system-mediated regulation of cardiac rhythm and vascular function in PCS. AAB levels did not correlate with B- and T-cell receptor repertoire metrics or TRBV gene usage.},
}

@article {pmid41273342,
year = {2025},
author = {Zuccarelli, L and Baldassarre, G and Bondesan, A and Caroli, D and De Micheli, R and Tringali, G and Favaretto, T and Suraj-Prazmowska, J and Kurpinska, A and Majerczak, J and Chlopicki, S and Zoladz, JA and Sartorio, A and Grassi, B},
title = {Impaired nitric oxide-dependent endothelial function in young male individuals with obesity before the onset of symptoms and complications.},
journal = {Experimental physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/EP093109},
pmid = {41273342},
issn = {1469-445X},
support = {//Italian Ministry of Health - ricerca corrente/ ; 2020EM9A8X//Ministero dell'Istruzione dell'Università e della Ricerca/ ; 2022LBBKHX//Ministero dell'Istruzione dell'Università e della Ricerca/ ; G53D23005610006//Ministero dell'Istruzione dell'Università e della Ricerca/ ; P2022XX7YL//Ministero dell'Istruzione dell'Università e della Ricerca/ ; G53D2300747000//Ministero dell'Istruzione dell'Università e della Ricerca/ ; //'Long-COVID syndrome: pathophysiology of the impaired exercise tolerance'/ ; //'Central (cardiorespiratory) and peripheral (muscular) determinants of functional deterioration in COPD: new biomarkers for evaluating disease severity and acute exacerbations?'/ ; N43/DBS/000221//Jagiellonian University Collegium Medicum/ ; N43/DBS/000315//Jagiellonian University Collegium Medicum/ ; 06/IDUB/2019/94//qLIFE Priority Research Area under the Excellence Initiative - Research University Programme at the Jagiellonian University/ ; },
abstract = {Endothelial dysfunction drives obesity-related complications. Doppler ultrasound measurement of blood flow during 1-min passive leg movements (PLM) is a valuable non-invasive tool for assessing endothelial function and nitric oxide (NO)-mediated vasodilation. The objectives of this work were t o identify endothelial dysfunction biomarkers in young individuals with obesity (OB) using the PLM test; to evaluate the effects of a rehabilitation programme on these biomarkers; and to explore associations between PLM data, oxidative metabolism and blood biomarkers of microvascular impairment. Fifteen male OB (age 17 ± 4 years; body mass 121.4 ± 24.1 kg; body mass index 39.3 ± 7.5 kg m[-2]) were tested before (PRE) and after (POST) a 3-week multidisciplinary body mass reduction programme. Fifteen age-matched normal-weight males (CTRL) underwent PRE measurements. Participants performed an incremental exercise, a PLM test and underwent blood biomarker analysis. Peak oxygen uptake and ventilatory thresholds (mL kg[-1] min[-1]) were ∼40% lower in OB versus CTRL (P < 0.001) and improved by ∼8% in OB POST versus PRE (P < 0.05). Plasma nitrite concentration was lower in OB (0.18 ± 0.09 µmol L[-1]) versus CTRL (0.51 ± 0.49; P = 0.02). Baseline blood flow, normalized for appendicular muscle mass, was similar between the two groups, whereas peak blood flow, Δpeak (difference between peak and baseline) and the area under the blood flow versus time curve were significantly lower in OB PRE, with improvements in OB POST. Several blood biomarkers of endothelial barrier function and permeability differed in OB versus CTRL. The blunted PLM-induced hyperaemic response and lower plasma nitrite levels indicate impaired endothelial function in young individuals with obesity, occurring before the onset of cardiovascular and metabolic complications.},
}

@article {pmid41272382,
year = {2025},
author = {Dornas, W and Reis, JP and Belilo, TE and Vaz, LG and Nasser, HH and de Souza Maia, ML and Figueiredo, A and Tcherniacovski, AG and Montenegro, LCC and Yang, X and C Santiago, H},
title = {Persistent inflammatory cytokine signature in long Covid-19 patients: a meta-analysis.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41272382},
issn = {1568-5608},
abstract = {Post-acute sequelae of Covid-19 (PASC) refer to persistent symptoms lasting weeks to months after acute SARS-CoV-2 infection. However, identifying biological mechanisms, potential therapeutic targets, and modifiable environmental risk factors remains necessary. Here, we analyzed cytokine levels in patients with PASC through a systematic literature search of the PubMed/MEDLINE, Web of Science, and Scopus databases, including articles published up to December 2024. A total of 33 studies (comprising 3294 patients) were included, addressing the long-term sequelae following acute Covid-19 infection. Levels of IL-6, IL-2, MCP-1/CCL2, TNF-α, IFN-γ, and IP-10/CXCL10 were higher in Covid-19 patients with PASC compared to those without PASC, suggesting an inflammatory basis for the persistence of symptoms. Conversely, little or no difference was observed for IL-1β, IL-7, IL-10, IL-4, IL-17A, IL-8, and IL-1α. To assess the duration of the sustained inflammatory response post-infection, cytokine measurements were categorized as < 6 months or ≥ 6 months after diagnosis. IL-6, MCP-1/CCL2, TNF-α, and IFN-γ remained elevated in both time windows, while IL-1β, IL-8, IP-10/CXCL10, IL-2, and IL-10 showed increased levels beyond 6 months post-Covid-19 diagnosis. Our findings indicate that persistent elevation of inflammatory cytokine is associated with PASC, contributing to a better understanding of the immune pathology underlying chronic dysfunction related to Covid-19.},
}

@article {pmid41271803,
year = {2025},
author = {Bansal, A},
title = {Economic burden of long COVID: macroeconomic, cost-of-illness and microeconomic impacts.},
journal = {NPJ primary care respiratory medicine},
volume = {35},
number = {1},
pages = {53},
pmid = {41271803},
issn = {2055-1010},
mesh = {Humans ; *COVID-19/economics/epidemiology ; *Cost of Illness ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Global Health ; Unemployment ; },
abstract = {Long COVID, defined by symptoms persisting three months post-SARS-CoV-2 infection, presents a significant global health and economic challenge, with global prevalence estimated at 36% (ranging from 1-92%). This brief communication consolidates current knowledge on its economic impacts, including macroeconomic, cost-of-illness, and microeconomic impacts, which are estimated at an average annual burden of $1 trillion globally and $9000 per patient in the USA, with some individuals covering substantial out-of-pocket expenses. Annual lost earnings in the USA alone are estimated at approximately $170 billion. Long COVID was associated with increased unemployment, financial distress, and work impairment for up to three years post-infection. This paper highlights discrepancies in impact estimation methodologies and calls for standardised metrics especially in emerging economies. Key research gaps include the absence of comprehensive longitudinal studies on individual and aggregated economic burden, specific long COVID phenotypes and biomarkers, and cost-effectiveness evaluations of interventions.},
}

Humans
*COVID-19/economics/epidemiology
*Cost of Illness
SARS-CoV-2
Post-Acute COVID-19 Syndrome
Global Health
Unemployment

@article {pmid41271424,
year = {2025},
author = {Seboka, BT and Smith, J and Whitmore, K and Baranow, B and Howden, E and Kulkarni, J and Huynh, QL and H Marwick, T},
title = {Depression as a moderator and mediator of functional status in patients with Long COVID: a cross-sectional and longitudinal observational study from the PERCEIVE cohort in Australia.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e099776},
doi = {10.1136/bmjopen-2025-099776},
pmid = {41271424},
issn = {2044-6055},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *COVID-19/psychology/complications/epidemiology/physiopathology ; Longitudinal Studies ; Middle Aged ; *Depression/epidemiology ; Adult ; SARS-CoV-2 ; Aged ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; Tasmania/epidemiology ; Victoria/epidemiology ; },
abstract = {BACKGROUND: In patients with post-acute sequelae of COVID-19 (PASC), depression has been associated with symptom severity, the duration since infection and ongoing functional impairment. However, the interconnections between these factors remain inadequately understood.

OBJECTIVES: This study aimed to explore the roles of depressive symptoms in moderating and mediating the relationships between post-COVID-19 conditions and functional capacity.

METHODS: The PERCEIVE study recruited 1794 participants from Victoria and Tasmania through online advertisements based on possible PASC for a cross-sectional study. Of these, 461 participated in the longitudinal study. Post-COVID-19 duration and symptoms were recorded, and depressive symptoms and functional capacity were self-reported using the 9-item Patient Health Questionnaire and the Duke Activity Status Index (DASI), respectively. The association of depression with functional capacity was explored using ordinary least squares (OLS) regression, with companion OLS models, Sobel-Goodman tests and 1000 bootstrap iterations to assess mediation. Longitudinal data were analysed to assess changes in functional capacity and depressive symptoms over time, with mediation analysis using mixed models to explore depression as a mediator.

RESULTS: Participants had a mean DASI score of 35 (SD 21). Fatigue (18%), shortness of breath (11%) and chest pain (6%) were common symptoms, with severe depression linked to fatigue (93%) and shortness of breath (66%). The severity of post-COVID-19 symptoms was associated with severe depression (β=6.31, 95% CI 5.42 to 7.21) and reduced functional capacity (β=-6.40, 95% CI -9.20 to -3.61), with depression mediating 36% of the association between post-COVID-19 symptom severity and functional capacity. PASC was associated with higher depression scores (β=2.06, 95% CI 1.15 to 2.97) and lower functional capacity (β=-3.99, 95% CI -6.21 to -1.77), with depression mediating 51% of the association between PASC and reduced functional capacity. The longitudinal analysis suggested that depression is associated with the relationship between PASC and changes in functional capacity over time (unstandardised estimate=-5.16, p<0.001).

CONCLUSION: Depression plays a key role in exacerbating post-COVID-19 functional impairment. This observation underscores the need for targeted physical and mental health interventions to enhance long-term recovery for those with severe conditions.},
}

Humans
Male
Female
Cross-Sectional Studies
*COVID-19/psychology/complications/epidemiology/physiopathology
Longitudinal Studies
Middle Aged
*Depression/epidemiology
Adult
SARS-CoV-2
Aged
Severity of Illness Index
Post-Acute COVID-19 Syndrome
Tasmania/epidemiology
Victoria/epidemiology

@article {pmid41269680,
year = {2025},
author = {Pant, S},
title = {Resistance Training Improves Long COVID Outcomes.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2025.19746},
pmid = {41269680},
issn = {1538-3598},
}

@article {pmid41269415,
year = {2025},
author = {de Almeida Gomes, I and Braga-Neto, P and Matos, TL and da Silva, EL and de Oliveira, LLB and Lima, LB and Tavares-Júnior, JWL and Moura, AEF and de Andrade, MH and de Maria Frota Vasconcelos, T and Oriá, RB and Oliveira, DN and Sobreira-Neto, MA and Souza, PFN and de Moraes, MEA and Mesquita, FP and Montenegro, RC},
title = {Associations Between APOE Polymorphisms, Neurological Symptoms, and Cognitive Assessments in Long COVID Patients: An Analysis of SNPs rs7412 and rs429358.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {113},
pmid = {41269415},
issn = {1559-1182},
mesh = {Humans ; *Polymorphism, Single Nucleotide/genetics ; Male ; Female ; *COVID-19/genetics/complications/psychology ; *Apolipoproteins E/genetics ; Middle Aged ; *Cognition/physiology ; Aged ; Genetic Predisposition to Disease ; Genetic Association Studies ; Alleles ; Genotype ; Adult ; },
abstract = {Long COVID has been associated with persistent neurological symptoms that impair cognitive function and quality of life, raising questions about the role of genetic factors in symptom severity and persistence. Apolipoprotein E (APOE) polymorphisms, known for their relevance in neurodegenerative diseases, may significantly influence neurological outcomes in long COVID patients. This study aimed to investigate the relationship between APOE polymorphisms, specifically single nucleotide polymorphisms (SNPs) rs7412 and rs429358, and neurological and cognitive symptoms in long-term COVID patients. APOE genotypes were identified through the analysis of SNPs rs7412 and rs429358. Cognitive and behavioral assessments were conducted using the Mini-Mental State Examination (MMSE), the Pfeffer Functional Activities Questionnaire, the Beck Inventory for mood assessment and the Epworth Sleepiness Scale (ESS). Statistical analyses included Mann-Whitney U test, chi-square or Fisher's exact test, and odds ratio calculation, using R Studio and GraphPad Prism. The results indicated that the ε2ε3 genotype was associated with lower scores on the BECK, suggesting fewer depressive symptoms, while the ε3ε3 genotype was linked to an increase in depressive symptoms. Furthermore, analyses of APOE alleles showed an opposite pattern concerning daytime sleepiness: carriers of the ε2 allele exhibited greater daytime sleepiness, whereas ε3 allele carriers reported less sleepiness, as measured by the ESS. The analysis of the rs7412 SNP revealed significant impacts on both BECK and ESS scores. These findings suggest that APOE polymorphisms, particularly the ε2 and ε3 alleles, play a crucial role in modulating neurological and cognitive symptoms associated with long COVID. The results highlight the potential of genetic screening to identify patients at higher risk of persistent cognitive and emotional alterations, emphasizing the importance of personalized management strategies and the need for further research in diverse populations.},
}

Humans
*Polymorphism, Single Nucleotide/genetics
Male
Female
*COVID-19/genetics/complications/psychology
*Apolipoproteins E/genetics
Middle Aged
*Cognition/physiology
Aged
Genetic Predisposition to Disease
Genetic Association Studies
Alleles
Genotype
Adult

@article {pmid41268552,
year = {2025},
author = {Rosa, BA and Bigham, M and Darling, TL and Arun, A and Singh, KS and Martin, J and Boon, ACM and Mitreva, M},
title = {Hookworm infection modulates lung and intestinal transcriptomic responses to SARS-CoV-2 in Syrian hamsters.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1701728},
pmid = {41268552},
issn = {1664-3224},
mesh = {Animals ; *COVID-19/immunology/genetics/virology ; *SARS-CoV-2/immunology/physiology ; *Transcriptome ; *Lung/immunology/virology/metabolism ; Mesocricetus ; *Intestines/immunology/virology ; Cricetinae ; Disease Models, Animal ; Coinfection/immunology ; *Ancylostoma/immunology ; *Hookworm Infections/immunology ; Humans ; Gene Expression Profiling ; Male ; },
abstract = {BACKGROUND: Helminth infections are widespread in resource-limited settings, and modulate host immune responses, with potential implications for viral coinfections. Intestinal helminths can alter susceptibility to respiratory viruses, but the mechanisms influencing SARS-CoV-2 infection outcomes remain poorly understood.

METHODS: Using the Syrian hamster model, we investigated the impact of prior infection with the human hookworm Ancylostoma ceylanicum on host responses to SARS-CoV-2. Tissue-specific transcriptional responses were compared among four groups: naive, hookworm-only, SARS-CoV-2-only, and coinfected with both pathogens, 3 and 6 days post-viral infection. Viral titers and weight loss were assessed, and RNA-seq transcriptome profiles from lung and intestinal tissues were interrogated to identify differentially expressed genes and cellular pathways.

RESULTS: Prior hookworm infection did not significantly alter viral titers or weight loss compared to SARS-CoV-2 infection alone, but distinct transcriptional signatures compared were identified compared to either single infection. Coinfection uniquely differentially regulated hematopoiesis and B cell-associated genes (e.g., ATF5, IGHM, JCHAIN) in the lungs, and immune and stress response pathways and inflammation-associated genes (e.g. FOLR2, PLA2GF, FABP3) in the intestine. Genes and pathways differentially regulated by SARS-CoV-2 alone, but with attenuated transcriptional responses in the lungs of coinfected hamsters were observed, including the loss of upregulation of toll-like receptor signaling and previously proposed host biomarkers for COVID-19 severity (CHI3L1, HMOX1), Long COVID (FCG4/FCGR3A and FST) and mortality (FST). In the intestine, hookworm-associated suppression of type I interferon-related genes (TAP1, IRF7) was reversed with SARS-CoV-2 coinfection, highlighting pathogen-specific modulation of innate antiviral signaling. Genes and pathways consistently differentially regulated by with SARS-CoV-2 were consistent with expectations, and many hemoglobin pathways were differentially regulated with hookworm in the intestine. CIBERSORT analysis was estimated relative leukocyte abundances in each sample cohort.

CONCLUSION: Our findings demonstrate that A. ceylanicum infection reshapes host transcriptional responses to SARS-CoV-2 in a tissue-specific manner, enhancing B cell immunity in the lung while driving intestinal inflammation. Hookworm-induced immune modulation attenuated key SARS-CoV-2-responsive genes and pathways, suggesting potential mechanisms for reduced disease severity observed in helminth-endemic regions. These findings establish a molecular framework to better understand helminth, SARS-CoV-2 and host immune interactions, with relevance for other respiratory viral infections.},
}

Animals
*COVID-19/immunology/genetics/virology
*SARS-CoV-2/immunology/physiology
*Transcriptome
*Lung/immunology/virology/metabolism
Mesocricetus
*Intestines/immunology/virology
Cricetinae
Disease Models, Animal
Coinfection/immunology
*Ancylostoma/immunology
*Hookworm Infections/immunology
Humans
Gene Expression Profiling
Male

@article {pmid41268373,
year = {2025},
author = {Calleja-Conde, J and Echeverry-Alzate, V and Sánchez-Diez, S and Giné, E and Bühler, KM},
title = {Severe alcohol use and COVID-19: implications for physical and mental health.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1640207},
pmid = {41268373},
issn = {1664-0640},
abstract = {The COVID-19 pandemic has revealed and intensified the vulnerability of individuals with pre-existing medical and behavioral conditions, notably those related to substance use. Among these, chronic alcohol consumption represents a clinically significant, yet often under-addressed, vulnerability factor that may exacerbate both the acute severity and long-term consequences of SARS-CoV-2 infection. This narrative review examines the biological and clinical intersections between alcohol use and COVID-19, focusing on shared mechanisms of immune dysfunction, neuroinflammation, and disruption of the gut-brain axis. We synthesize current findings showing that both conditions compromise innate and adaptive immune responses, alter cytokine signaling, and weaken mucosal and blood-brain barriers. These changes contribute to cognitive and emotional dysregulation and may increase the risk of persistent neuropsychiatric symptoms, including those observed in Long COVID. In addition, we discuss how chronic alcohol use may alter host susceptibility to infection and affect the immune response to vaccination, with implications for treatment outcomes and recovery. Our findings highlight the need to integrate alcohol use disorder into COVID-19 risk assessments, clinical management, and long-term mental health care planning. A multidisciplinary approach is essential to address the overlapping biological pathways that link alcohol-related vulnerability to COVID-19 outcomes.},
}

@article {pmid41267377,
year = {2025},
author = {},
title = {Correction to "The effect of uninterrupted and interrupted sitting on vascular function in adults with long COVID".},
journal = {Physiological reports},
volume = {13},
number = {22},
pages = {e70658},
doi = {10.14814/phy2.70658},
pmid = {41267377},
issn = {2051-817X},
}

@article {pmid41266487,
year = {2025},
author = {Richards-Belle, A and Shafran, R and Rojas, NK and Stephenson, T and Carr, E and Chalder, T and Dalrymple, E and McOwat, K and Simmons, R and Pinto Pereira, SM and , },
title = {Fatigue in children and young people up to 24 months after infection with SARS-CoV-2.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {41105},
pmid = {41266487},
issn = {2045-2322},
support = {COV-LT-0022//National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI)/ ; MR/Y009398/1//UK Medical Research Council/ ; },
mesh = {Humans ; Child ; *COVID-19/complications/virology/epidemiology ; Female ; Male ; *Fatigue/etiology/epidemiology/diagnosis ; Adolescent ; Longitudinal Studies ; SARS-CoV-2/isolation & purification ; Cross-Sectional Studies ; Post-Acute COVID-19 Syndrome ; },
abstract = {Persistent fatigue is common following acute SARS-CoV-2 infection. Little is known about post-infection fatigue trajectories in children and young people (CYP). This paper reports on a longitudinal analysis of the Children and Young People with Long COVID study. SARS-CoV-2-positive participants, aged 11-to-17-years at enrolment, responding to follow-ups at 3-, 6-, 12-, and 24-months post-infection were included. Fatigue was assessed via the Chalder Fatigue Scale (CFQ; score range: 0-11, with ≥4 indicating clinical case-ness) and by a single-item (no, mild, severe fatigue). Fatigue was described cross-sectionally and examined longitudinally using linear mixed-effects models. Among 943 SARS-CoV-2-positive participants, 581 (61.6%) met CFQ case-ness at least once during follow-up. A higher proportion of ever-cases (vs. never-cases) were female (77.1% vs. 54.4%), older (mean age 15.0 vs. 13.9 years), and met Post-COVID Condition criteria 3-months post-infection (35.6% vs. 7.2%). The proportion of CFQ cases increased from 35.0% at 3-months to 40.2% at 24-months post-infection; 15.9% meet case-ness at all follow-ups. Single-item mild/severe responses showed sensitivity (≥0.728) and specificity (≥0.755) for CFQ case ascertainment. On average, CFQ scores increased by 0.448 points (95% CI, 0.252 to 0.645) over 24-months, but there were subgroup differences (e.g., fatigue increased faster in females than males and improved slightly in those meeting Post-COVID Condition criteria 3-months post-infection while worsening in those not meeting criteria). Persistent fatigue was prominent in CYP up to 24 months after infection. Subgroup differences in scores and trajectories highlight the need for targeted interventions. Single-item assessment is a practical tool for screening significant severe fatigue.},
}

Humans
Child
*COVID-19/complications/virology/epidemiology
Female
Male
*Fatigue/etiology/epidemiology/diagnosis
Adolescent
Longitudinal Studies
SARS-CoV-2/isolation & purification
Cross-Sectional Studies
Post-Acute COVID-19 Syndrome

@article {pmid41265281,
year = {2025},
author = {da Silva, EM and de Campos, CM and de Godoy, CG and de Oliveira, DB and Alonso, AC and da Silva, VC and Schmitt, ACB and Ochiai, GS and Viana, BOC and da Silva, JM and de Carvalho, CRF and de Carvalho, CRR and D'Andréa Greve, JM and Pompeu, JE},
title = {Predictors of persistent fatigue one year after severe COVID-19: A prospective cohort study on depression and lung function.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100846},
doi = {10.1016/j.clinsp.2025.100846},
pmid = {41265281},
issn = {1980-5322},
abstract = {BACKGROUND: Fatigue is among the most enduring symptoms of long COVID. However, the relationship between persistent fatigue and factors such as physical performance, lung function, anxiety, and depression in severe cases of COVID-19 remains underexplored.

OBJECTIVES: To assess the prevalence of fatigue and its association with these factors in patients one year after severe COVID-19 hospital discharge.

METHODS: This cohort comprised participants aged 18-years and older diagnosed with COVID-19. Evaluations were conducted at one, four, six-, and twelve-months following hospital discharge. Clinical data were collected, which included assessments of fatigue - Functional Assessment of Chronic Illness Therapy Fatigue subscale, lung capacity ‒ Spirometry, physical performance - 1-minute Sit to Stand Test, psychological aspects - Hospital Anxiety and Depression Scale, and functional capacity - Barthel index.

RESULTS: Of the 162 participants, 50 % experienced fatigue one-month post-discharge and this prevalence gradually decreased to 36 % by the end of one-year period. The fatigue group had a median age of 58-years. It was predominantly composed of women, with a majority identifying as non-white and having a body mass index greater than 30 kg/m[2]. Physical performance assessments within the fatigue group showed no significant changes over time, whereas lung capacity demonstrated significant improvement only at the 12-month mark. Additionally, anxiety and depression levels were significantly higher in the fatigue group over time (p < 0.05).

CONCLUSIONS: Fatigue persisted in 36 % of participants one-year post-hospital discharge. The potential predictors of long-term fatigue were depressive symptoms and impaired lung function observed within the first month after hospital discharge. Therefore, the authors highlight the importance of screening and monitoring these aspects in order to enable early intervention in this population.},
}

@article {pmid41264615,
year = {2025},
author = {Uwakwe, CK and Rangan, ES and Kumar, S and Gutjahr, G and Miao, X and Brooks, AW and Maguire, P and Mishra, T and McGuire, L and Snyder, MP},
title = {Longitudinal wearable sensor data enhance precision of Long COVID detection.},
journal = {PLOS digital health},
volume = {4},
number = {11},
pages = {e0001093},
doi = {10.1371/journal.pdig.0001093},
pmid = {41264615},
issn = {2767-3170},
abstract = {Despite the millions of individuals struggling with persistent symptoms, Long COVID has remained difficult to diagnose due to limited objective biomarkers, often leading to underdiagnosis or even misdiagnosis. To bridge this gap, we investigated the potential of utilizing wearable sensor data to aid in the diagnosis of Long COVID. We analyzed longitudinal heart rate (HR) data from 126 individuals with acute SARS-CoV-2 infections to develop machine learning models capable of predicting Long COVID status using derived HR features, symptom features, or a combination of both feature sets. The HR features were derived across six analytical categories, including time-domain, Poincaré nonlinear, raw signal, Kullback-Leibler (KL) divergence, variational mode decomposition (VMD), and the Shannon energy envelope (SEE), enabling the capture of heart rate dynamics over various temporal scales and the quantification of day-to-day shifts in HR distributions. The symptom features used in the final models included chest pain, vomiting, excessive sweating, memory loss, brain fog, heart palpitations, and loss of smell. The combined HR- and symptom-feature model demonstrated robust predictive performance, achieving an area under the Receiver Operating Characteristic curve (ROC-AUC) of 95.1% and an area under the Precision-Recall curve (PR-AUC) of 85.9%. These values represent a significant improvement of approximately 5% in both the ROC-AUC and PR-AUC over the symptoms-only model. At the population level, this improvement in discrimination could lead to clinically meaningful reductions in misclassification and improved patient outcomes, achieved through a non-invasive diagnostic tool. These findings suggest that wearable HR data could be used to derive an objective biomarker for Long COVID, thereby enhancing diagnostic precision.},
}

@article {pmid41262872,
year = {2025},
author = {Lv, X and Ji, L and Cao, W and Xue, Y and Dai, H and Zhang, S},
title = {Revisiting lung cancer immunotherapy in the era of long COVID: mechanistic insights and therapeutic implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1657691},
pmid = {41262872},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/immunology/complications ; *Immunotherapy/methods ; *Lung Neoplasms/therapy/immunology ; SARS-CoV-2/immunology ; Tumor Microenvironment/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; },
abstract = {In the post-COVID-19 era, understanding the long-term impact of Long COVID on the immune system is essential for deciphering its influence on lung cancer pathogenesis and immunotherapeutic efficacy. This review comprehensively examines how persistent COVID-19 sequelae-manifested as chronic inflammation, pulmonary fibrosis, cytokine dysregulation, and T-cell exhaustion can reshape the lung cancer microenvironment. In addition, the emerging roles of memory B cells and altered neutrophil function in promoting tumorigenesis are discussed. Importantly, we analyze recent clinical evidence suggesting that COVID-19 vaccination may enhance the efficacy of immune checkpoint inhibitors, potentially by modulating host immunity. By integrating mechanistic insights with clinical observations, this review aims to illuminate the challenges and opportunities at the intersection of Long COVID and lung cancer treatment, thereby fostering the development of personalized therapeutic strategies in the post-pandemic era.},
}

Humans
*COVID-19/immunology/complications
*Immunotherapy/methods
*Lung Neoplasms/therapy/immunology
SARS-CoV-2/immunology
Tumor Microenvironment/immunology
Immune Checkpoint Inhibitors/therapeutic use

@article {pmid41262358,
year = {2025},
author = {Goertzen, SM and Lindholm, DA and Walter, RJ and Huprikar, NA and Ganesan, A and Richard, SA and Mende, K and Harrell, TE and Peterson, PG and Simons, M and Tribble, DR and Agan, BK and Burgess, TH and Pollett, SD and Morris, MJ},
title = {Clinical, Radiographic, and Physiological Correlates of Post-COVID-19 Dyspnea in Military Health System Beneficiaries: Results From the Chronic Impairment With Pulmonary Symptoms (ChIPS) Sub-study.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf633},
pmid = {41262358},
issn = {2328-8957},
abstract = {BACKGROUND: Dyspnea has been described in up to 10-30% of patients post-SARS-CoV-2 infection. The underlying pathology for these persistent symptoms remains poorly understood. This study aimed to characterize changes in cardiopulmonary anatomical structure and physiology that may explain ongoing dyspnea after COVID-19.

METHODS: Participants had a history of symptomatic COVID-19, were between 18 and 65 years of age, and without significant pre-existing cardiopulmonary disease. Each participant underwent prospective chest high resolution computed tomography (HRCT), transthoracic echocardiography (TTE), electrocardiogram (ECG), pulmonary function testing (PFT) with lung volumes and diffusing capacity for carbon monoxide (DLCO), impulse oscillometry (IOS), and a six-minute walk test (6MWT) with Borg dyspnea scoring.

RESULTS: Among 115 enrolled participants, 39 had persistent dyspnea. The mean forced expiratory volume at 1 s/forced vital capacity (FEV1/FVC) ratio was higher in those with persistent dyspnea, but within normal ranges for both groups. There were no other statistically significant differences in FEV1, FVC, and DLCO between the groups. Those with ongoing dyspnea had a decreased walk distance (difference of 50.4 m, P = .01). Resting and post-6MWT Borg scores were 0.9 and 1.3 higher in those with persistent dyspnea, respectively (P-values <.001). There were no significant differences in IOS, HRCT, TTE, or ECG findings between groups.

CONCLUSIONS: This study demonstrated a difference in 6MWT distance and Borg scores between those with and without persistent dyspnea. There were no clear PFT, cardiac test, or HRCT findings that explained these persistent symptoms. Overall, this study demonstrates both subjective and objective differences between those with ongoing dyspnea following COVID-19 that are not explained by standard investigations typically ordered in clinical care for chronic dyspnea. These findings underscore the importance of further research into the etiology of post-COVID-19 dyspnea, including other investigations which may detect more subtle alterations in pulmonary physiology.},
}

@article {pmid41260143,
year = {2025},
author = {El Hajjar, AH and Zalaquett, Z and Rosenzveig, A and Syed, AB and Al-Dalakta, A and Majeed, Z and Villalonga, M and Ikram, J and Ehsan, M and Motairek, I and Heine, M and Berglund, F and Wang, TKM and Klein, A},
title = {Investigating Pericarditis Diagnosis in a Tertiary Pericardial Center: A Descriptive Study.},
journal = {JACC. Advances},
volume = {4},
number = {12 Pt 2},
pages = {102335},
doi = {10.1016/j.jacadv.2025.102335},
pmid = {41260143},
issn = {2772-963X},
abstract = {BACKGROUND: Pericarditis diagnosis can be challenging due to its nonspecific presentation, which may lead to frequent misdiagnosis.

OBJECTIVES: In this study, the authors aimed to report the rate of misdiagnosed pericarditis and describe the characteristics of these patients.

METHODS: Between September 2022 and September 2023, patients referred to the Pericardial Center with a diagnosis of pericarditis were enrolled in a prospective registry. Data were collected using a standardized history and physical examination template. Diagnosis was established according to the 2015 European Society of Cardiology guidelines. The prevalence of misdiagnosed pericarditis was calculated. Demographics, comorbidities, symptoms, laboratory results, and imaging were compared between the accurately diagnosed (group 1) and misdiagnosed pericarditis cohorts (group 2).

RESULTS: A total of 170 patients were included; the mean age was 49.1 years. Thirty-five percent of patients were misdiagnosed. Demographics were similar in both groups. Significant differences were found between group 1 and group 2) in coronary artery disease (17.3% vs 5.0%, P = 0.02), valvular disease (23.6% vs 8.3%, P = 0.01), and atrial fibrillation (24.5% vs 6.7%, P < 0.01). Significant late gadolinium enhancement on magnetic resonance imaging, raised inflammatory markers, electrocardiogram changes, and specific pericardial pain were more common in the accurately diagnosed group (P < 0.05). COVID-19 infection was significantly higher in the misdiagnosed group (16.7% vs 6.4%, P < 0.05), whereas cardiac surgery was significantly lower (3.3% vs 18.2%, P < 0.05).

CONCLUSIONS: Thirty-five percent of patients referred to the pericardial center are misdiagnosed with pericarditis. Inflammatory markers and late gadolinium enhancement on magnetic resonance imaging can help refine the diagnosis. COVID-19 infection is associated with higher rates of misdiagnosis.},
}

@article {pmid41259895,
year = {2025},
author = {Ben, ÂJ and Kisiangani, I and Kinya, I and Wynberg, E and de Jong, MD and Schultsz, C and Asiki, G and Vassall, A},
title = {Long-Term Changes in Health-Related Quality of Life and Economic Burden After a SARS-CoV-2 Infection: Analysis of the Long COVID Prospective Cohort Study in Nairobi.},
journal = {Value in health regional issues},
volume = {53},
number = {},
pages = {101545},
doi = {10.1016/j.vhri.2025.101545},
pmid = {41259895},
issn = {2212-1102},
abstract = {OBJECTIVES: To characterize long-term changes in health-related quality of life (HRQoL) and factors associated with catastrophic expenditures and catastrophic costs after a SARS-CoV-2 infection.

METHODS: Data from 291 participants of the Long COVID Prospective Cohort Study in Nairobi were analyzed. Participants were enrolled between 2022 and 2023 and followed up for 12 months. Possible factors and outcomes (HRQoL, catastrophic expenditures, and catastrophic costs) were measured every 3 months. Changes in outcomes over time were assessed using generalized estimating equations.

RESULTS: HRQoL was significantly reduced by 11.4% (95% CI -16.3% to -6.5%), 8.6% (95% CI -12.5% to -4.6%), 6.1% (95% CI -10.5% to -1.8%), and 4.1% (95% CI -7.9% to -0.3%) at 6, 9, 12, and 15 months after a positive polymerase chain reaction test, respectively, compared with the period before COVID-19. HRQoL was significantly reduced by 3.3% (95% CI -6.2% to -0.5%), and 10.9% (95% CI -16.5% to -5.3%), respectively, in participants with any COVID-19-related symptoms or fatigue. Older age (odds ratio [OR] 5.83, 95% CI 2.11 to 16.15), no COVID-19 vaccination (OR 5.83, 95% CI 2.11 to 16.15), any COVID-19-related symptoms (OR 2.22, 95% CI 1.15 to 4.28), and pay cut or reduced income due to COVID-19-related symptoms (OR 17.36, 95% CI 2.28 to 132.07) were associated with high odds of experiencing catastrophic expenditures. Severe/critical SARS-CoV-2 infection (OR 4.77, 95% CI 1.72 to 13.25) and fatigue (OR 2.27, 95% CI 1.03 to 4.96) significantly increased the odds of experiencing catastrophic costs, whereas better HRQoL (OR 0.12, 95% CI 0.02 to 0.57) and social support (OR 0.30, 95% CI 0.09 to 0.93) decreased the odds.

CONCLUSIONS: HRQoL remains reduced up to 15 months after a SARS-CoV-2 infection compared with pre-COVID-19 levels, with participants in better health and socioeconomic status less likely to experience catastrophic expenditures and catastrophic costs.},
}

@article {pmid41259457,
year = {2025},
author = {Hi, EMB and Bianchi, CCR and Gritte, RB and Klauss, PHA and Leal, NFSM and Oliveira, IS and Barros, MFCB and Soriano, FG and Curi, R and Machado, MCC},
title = {Detection of autoantibodies in severe COVID-19 patients two years after hospital discharge.},
journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica},
volume = {58},
number = {},
pages = {e14927},
doi = {10.1590/1414-431X2025e14927},
pmid = {41259457},
issn = {1414-431X},
mesh = {Humans ; *COVID-19/immunology/blood ; Middle Aged ; Male ; Female ; Aged ; *Autoantibodies/blood ; Adult ; Aged, 80 and over ; SARS-CoV-2/immunology ; Young Adult ; Biomarkers/blood ; Brazil ; Patient Discharge ; Procalcitonin/blood ; Antibodies, Antinuclear/blood ; C-Reactive Protein/analysis ; Case-Control Studies ; Rheumatoid Factor/blood ; Severity of Illness Index ; },
abstract = {After SARS-CoV-2 infection, severe COVID-19 may develop with persistent sequelae, even after hospital discharge. This condition may result from tissue damage or immune alterations caused by the virus, including immune dysregulation, hyperinflammation, loss of immune tolerance, excessive neutrophil extracellular trap (NET) production, and antibody cross-reactivity (molecular mimicry), which can promote autoantibody development. This study evaluated autoantibody expression in patients with long COVID-19 and its potential relationship with symptoms. Conducted in Baixada Santista, São Paulo, Brazil, the study involved 55 participants aged 21-85 years who had tested positive for SARS-CoV-2. Blood samples were collected two years post-discharge, and serum was analyzed for inflammatory and autoimmune markers, including antinuclear antibody (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), procalcitonin (PCT), Venereal Disease Research Laboratory test (VDRL), and C-reactive protein (CRP). Results were compared to a control group of 21 individuals who never tested positive for COVID-19. Among severe COVID-19 patients, 26 reacted to ANA, 16 to VDRL, 2 had elevated RF, 12 had increased PCT, and 11 had high CRP, whereas the control group showed no reactive results. Anti-CCP values were not significant. Findings suggest that hyperinflammation may contribute to autoimmunity, particularly in cases of reactive ANA levels, linking COVID-19 symptoms to autoimmune responses.},
}

Humans
*COVID-19/immunology/blood
Middle Aged
Male
Female
Aged
*Autoantibodies/blood
Adult
Aged, 80 and over
SARS-CoV-2/immunology
Young Adult
Biomarkers/blood
Brazil
Patient Discharge
Procalcitonin/blood
Antibodies, Antinuclear/blood
C-Reactive Protein/analysis
Case-Control Studies
Rheumatoid Factor/blood
Severity of Illness Index

@article {pmid41259430,
year = {2025},
author = {Braga, F and Espinosa, G and Monteiro, A and Milani, M and Paiva, J and Milani, JGPO and Franzoni, L and Stein, R and Cipriano, G and Gurgel, JL and Mourilhe-Rocha, R},
title = {Cardiopulmonary Resilience in Highly Active Individuals: Pre-Post COVID-19 Cardiopulmonary Exercise Testing Analysis.},
journal = {Arquivos brasileiros de cardiologia},
volume = {122},
number = {9},
pages = {e20250094},
doi = {10.36660/abc.20250094},
pmid = {41259430},
issn = {1678-4170},
mesh = {Humans ; *COVID-19/physiopathology/complications ; Male ; *Exercise Test/methods ; Female ; Retrospective Studies ; Adult ; Oxygen Consumption/physiology ; Middle Aged ; *Exercise Tolerance/physiology ; SARS-CoV-2 ; Time Factors ; },
abstract = {BACKGROUND: The COVID-19 pandemic has affected millions globally, with persistent impacts extending beyond the acute phase. One such effect is post-COVID (long COVID), characterized by symptoms such as fatigue and exercise intolerance lasting more than 60 days. Although regular exercise is associated with reduced risk of severe outcomes, reports of decreased athletic performance after COVID-19 - even among highly active individuals (HAIs) - have raised concerns regarding the long-term effects on physical health. Cardiopulmonary exercise testing (CPET) is a valuable tool to assess exercise intolerance and to investigate the metabolic and ventilatory consequences of COVID-19.

OBJECTIVES: To evaluate the impact of COVID-19 on cardiopulmonary function in HAIs by analyzing metabolic and ventilatory responses using CPET before and after infection.

METHODS: CPET data were retrospectively analyzed from HAIs of both sexes. Primary outcomes included changes in peak oxygen uptake (V ⋅ O2peak) and ventilatory efficiency (V ⋅ E/ V ⋅ CO2 slope). Statistical significance was set at 5% (p < 0.05).

RESULTS: A total of 43 HAIs (72.1% male; 44 ± 10 years) were included. The median interval between CPETs was 479 days, with testing performed a mean of 44 ± 27 days after COVID-19. V ⋅ O2peak decreased by a mean of 1.5 mL/kg/min (p = 0.017), representing a 3.84% reduction in predicted V ⋅ O2peak values (p = 0.045). V ⋅ E/ V ⋅ CO2 slope increased by 1.2 (p = 0.017).

CONCLUSION: Although HAIs are not immune to the effects of COVID-19, their high baseline physical activity levels appear to confer substantial cardiopulmonary resilience. Only minimal post-infection alterations were observed, which suggests that maintaining fitness may provide protective benefits against long-term sequelae of COVID-19.},
}

Humans
*COVID-19/physiopathology/complications
Male
*Exercise Test/methods
Female
Retrospective Studies
Adult
Oxygen Consumption/physiology
Middle Aged
*Exercise Tolerance/physiology
SARS-CoV-2
Time Factors

@article {pmid41256779,
year = {2025},
author = {Alemdaroğlu, E and Önal, R and Dizdar, D and Güler, T and Altaş, EU and Kutay Ordu Gökkaya, N},
title = {Continuous versus low-intensity interval aerobic exercise in pulmonary rehabilitation after COVID-19.},
journal = {Turkish journal of physical medicine and rehabilitation},
volume = {71},
number = {3},
pages = {385-394},
pmid = {41256779},
issn = {2587-1250},
abstract = {OBJECTIVES: This study aimed to compare the effectiveness of mild-moderate intensity continuous training (CT) and low-intensity interval moderate-intensity training (LIIT) aerobic exercises in pulmonary rehabilitation after coronavirus disease 2019 (COVID-19).

PATIENTS AND METHODS: This prospective study was conducted between January 2021 and January 2022. Sixty-three patients (47 males, 16 females; mean age: 54.3±11.3 years; range, 25 to 81 years) with one or more residual symptoms following COVID-19 infections were randomly included in the CT (n=33) or LIIT (n=30) groups. Fifteen sessions (60 min, 3-5/week) of aerobic exercise (20-min 40% of peak workload for CT; 40% peak workload with 3-min loaded and 1-min nonloaded intervals for LIIT, with 5 min warm-up and cool-down), breathing, and upper extremity strengthening exercises were applied. Outcome measures were symptom-limited submaximal exercise test, and six-minute walk test (6MWT), the modified Medical Research Council (mMRC) dyspnea scale, modified Borg dyspnea scale, and Borg 6-20 rate of perceived exertion scale, hand grip strength, fat-free mass, Hospital Anxiety and Depression Scale (HADS), and 36-item Short-Form Health Survey.

RESULTS: The maximum load and time reached during the exercise test, the 6MWT distance, hand grip strength, mMRC, HADS, and SF-36 scores significantly improved in both groups (p<0.05). Resting modified Borg dyspnea scores, heart rate, rate of perceived exertion, and oxygen supplementation requirement decreased significantly in the LIIT group (p<0.05). All posttreatment measures were similar in both groups (p>0.05). The changes in mMRC, resting heart rate, and 6MWT distance were significantly higher in the LIIT group compared to the CT group (p<0.05).

CONCLUSION: Both CT and LIIT improved functional capacity, dyspnea, tachycardia, depression, and quality of life measures safely and effectively in COVID-19 survivors with residual symptoms. Patients with poor clinical status who cannot tolerate CT after an acute pulmonary condition such as COVID-19 may benefit from LIIT.},
}

@article {pmid41256693,
year = {2025},
author = {Arish, M and Chaudhuri, AS and Tang, J and Narasimhan, H and Fang, A and Tang, J and Wei, X and Li, C and Cheon, IS and Qian, W and Naz, F and Almeida-Santos, G and Young, SP and Parimon, T and Shim, YM and Vassallo, R and Chen, P and Sun, J},
title = {Targeting a macrophage stemness factor to mitigate diseases post respiratory viral infection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.03.680366},
pmid = {41256693},
issn = {2692-8205},
abstract = {Tissue-resident alveolar macrophages (AMs) rely on intrinsic stem-like programs for self-renewal and maintenance, yet the transcriptional networks that support these functions and their relevance to post-viral lung disease remain largely unknown. Here, we identify TCF4 (Tcf7l2) as a critical transcription factor that governs AM maturation and stemness. Loss of TCF4 impaired AM proliferation, shifted their identity toward a pro-inflammatory phenotype, and exacerbated host morbidity following influenza or SARS-CoV-2 infection. Conversely, enforced TCF4 expression promoted the expansion of mature AMs, and supported lung recovery, thereby protecting against severe acute viral disease. Mechanistically, TCF4 antagonized β-catenin-driven inflammatory transcription while preserving oxidative phosphorylation, defining a reciprocal regulatory axis essential for AM function. Notably, respiratory viral infections and exuberant interferon signaling suppressed TCF4 expression, which remains chronically reduced in murine and human lungs with post-COVID fibrosis. This downregulation is associated with persistent KRT8 [hi] dysplastic epithelium and collagen deposition. Moreover, aging diminished TCF4 levels and enforced TCF4 expression dampened age-associated decline of AM self-renewal. Furthermore, in vivo TCF4 overexpression after viral clearance enhanced mature AM accumulation, promoted lung epithelium regeneration, attenuated chronic tissue fibrosis and restored pulmonary physiologial function in aged lungs in a model of persistent pulmonary fibrosis post-acute viral infection. These findings have established TCF4 as a key regulator of AM stemness and identified a promising therapeutic target for long COVID and related chronic lung diseases through the modulation of embryonic-derived macrophage regenerative capacity by targeting TCF4.},
}

@article {pmid41255761,
year = {2025},
author = {Sularea, VM and Townsend, L and Reid, C and Atanasescu, AV and Dyer, AH and Giangrazi, F and Lawrence, RR and Sivan, M and Moran, B and Doherty, DG and Conlon, NP and Long, A and O'Farrelly, C},
title = {Digitally Assessed Long COVID Symptomatology Is Associated With Lymphocyte Mitochondrial Dysfunction and Altered Immune Potential.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf447},
pmid = {41255761},
issn = {2328-8957},
abstract = {BACKGROUND: Postacute sequelae of SARS-CoV-2 infection, also known as long COVID (LC), is a complex and heterogenous condition affecting millions worldwide with a poorly understood underlying pathology. Although metabolic dysregulations have been described in LC, it remains unclear whether circulating immune cells exhibit immunometabolic alterations.

METHODS: We conducted a detailed clinical, immunologic, and mitochondrial analysis on 27 patients with LC and 27 who recovered from COVID-19 and were healthy. Symptom burden and severity were assessed and quantified via a digital platform with the modified COVID-19 Yorkshire Rehabilitation Scale. Mitochondrial function of circulating immune cell populations (lymphocytes and monocytes) was analyzed by measuring mitochondrial mass and mitochondrial membrane potential. Production of 11 cytokines after whole blood stimulation with bacterial and viral agonists was measured by multiplex immunoassay. Relationships between mitochondrial and immune parameters with LC symptoms were investigated.

RESULTS: Patients with LC exhibited significant symptom burden, with worsening across all symptom domains as compared with their health state before SARS-CoV-2 infection. They also had a decreased mitochondrial membrane potential of CD56[bright] natural killer cells, particularly in patients experiencing dizziness, whereas reduced mitochondrial membrane potential in CD4+ lymphocytes was found in patients with worsening breathlessness. Upon LPS stimulation, patients with LC demonstrated significantly lower IFN-γ production. In response to viral ligand R848, impaired IFN-β and IL-10 responses were associated with worsening cough and executive functions.

CONCLUSIONS: Symptom severity in LC is associated with immune cell mitochondrial dysfunction and altered cytokine responses, highlighting potential disease biomarkers and targets for future therapeutic strategies.},
}

@article {pmid41254881,
year = {2025},
author = {Kartal Öztürk, G and Böncüoğlu, E and Kıymet, E and Şahinkaya, Ş and Cem, E and Yılmaz Çelebi, M and Kara, AA and Karkıner, CŞ and Bayram, SN and Devrim, İ},
title = {Long-term follow-up of children after COVID-19 infection and monitoring pulmonary functions.},
journal = {Pediatrics international : official journal of the Japan Pediatric Society},
volume = {67},
number = {1},
pages = {e70274},
doi = {10.1111/ped.70274},
pmid = {41254881},
issn = {1442-200X},
mesh = {Humans ; *COVID-19/complications/physiopathology/epidemiology ; Child ; Male ; Female ; Adolescent ; Follow-Up Studies ; Respiratory Function Tests ; Child, Preschool ; Infant ; Prospective Studies ; *Lung/physiopathology ; },
abstract = {BACKGROUND: The severe acute respiratory syndrome coronavirus 2 is now part of our lives. Many children still experience post-COVID respiratory conditions and require evaluation and follow-up.

METHODS: Children referred to the Pediatric Pulmonology Department between 2021 and 2022, due to a history of COVID-19 pneumonia with/without comorbid disease and respiratory complaints after COVID-19, were prospectively followed up with pulmonary function tests at 3, 6, and 12 months.

RESULTS: The median age of 138 children was 14 years (1-18), 42 (30.4%) had comorbid conditions, and 40 (28.9%) had a history of COVID-19 pneumonia. Respiratory symptoms after infection persisted in approximately 62% of children, and 28% of children who had no symptoms before infection were diagnosed with asthma (N = 18, 13%), allergic rhinitis (N = 5), anxiety and tic disorder (N = 4), and other diseases (N = 4). At admission, pulmonary function abnormalities were detected in 12% (N = 4 obstructive ventilatory pattern, N = 6 restrictive, and N = 2 mixed). Pulmonary functions were similar in children with and without persistent respiratory complaints (PRCs). At the 12-month follow-up, there were three children (2.1%) with PRC, and pulmonary function anomalies persisted in five children. A significant increase in pulmonary function was observed in both children with and without PRC. FEF25-75, the indicator of small airways, was lower in children with PRC.

CONCLUSIONS: This study suggested that COVID-19 may have affected pulmonary function in children independently of respiratory symptoms and that this effect may be more severe in children with PRC. It is necessary to follow up and research examination and early intervention methods for post-COVID conditions.},
}

Humans
*COVID-19/complications/physiopathology/epidemiology
Child
Male
Female
Adolescent
Follow-Up Studies
Respiratory Function Tests
Child, Preschool
Infant
Prospective Studies
*Lung/physiopathology

@article {pmid41254361,
year = {2025},
author = {Stiles, LE and Larsen, NW and Eastin, EF and Miglis, MG},
title = {Response to letter by Zadeh et al. regarding "Chronic autonomic symptom burden in long-COVID: a follow-up cohort study".},
journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society},
volume = {},
number = {},
pages = {},
pmid = {41254361},
issn = {1619-1560},
}

@article {pmid41253410,
year = {2025},
author = {Volckaerts, T and Ruttens, D and Quadflieg, K and Burtin, C and Cops, D and De Soomer, K and Roelant, E and Verhaegen, I and Daenen, M and Criel, M and Vissers, D and Lapperre, T},
title = {Improved functional exercise capacity after primary care pulmonary rehabilitation in patients with long COVID (PuRe-COVID): a pragmatic randomised controlled trial.},
journal = {BMJ open respiratory research},
volume = {12},
number = {1},
pages = {},
doi = {10.1136/bmjresp-2025-003653},
pmid = {41253410},
issn = {2052-4439},
mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/rehabilitation/physiopathology/complications ; *Exercise Tolerance/physiology ; Primary Health Care ; Adult ; Walk Test ; SARS-CoV-2 ; *Exercise Therapy/methods ; Aged ; Hand Strength ; Treatment Outcome ; Fatigue ; Dyspnea ; Patient Reported Outcome Measures ; },
abstract = {BACKGROUND: Pulmonary rehabilitation (PR) improves physical status and symptoms in patients with long COVID, but access to specialised hospital-based centres is challenging. This trial studied the effect of primary care PR on functional exercise capacity and symptoms in patients with long COVID.

METHODS: In this pragmatic randomised controlled trial (PuRe-COVID), patients with long COVID were randomised to a 12-week stepwise PR programme in primary care, or to a control group without PR. The primary end point was change in 6 min walk distance (6MWD) from baseline to 12 weeks. Additional outcomes, measured at 6, 12, 24 and 36 weeks, included patient-reported outcomes, physical activity, maximal inspiratory (MIP) and expiratory pressures and hand grip strength.

RESULTS: In total, 76 patients were randomised (PR/control group (n=39/37); mean age 49±13 years). The change in 6MWD at 12 weeks was estimated to be +39 m in the PR group compared with the control group (95% CI (18 to 59), p<0.001). Furthermore, a decrease in Checklist Individual Strength (CIS)-fatigue was found for the PR group (-6 points; 95% CI (-10 to -2), p=0.011). At 12 weeks, patients in the intervention group were more likely to have a clinically significant improvement in 6MWD (OR 5.7, 95% CI (2.0 to 16.1), p=0.001), CIS-fatigue (OR 3.8, 95% CI (1.2 to 12.0), p=0.020), MIP (OR 3.7, 95% CI (1.05 to 12.7), p=0.036) and modified Medical Research Council dyspnoea score (OR 5.2, 95% CI (1.6 to 16.4), p=0.003).

CONCLUSIONS: Primary care stepwise individual PR may improve functional exercise capacity, fatigue and dyspnoea in patients with long COVID. It therefore may be a promising treatment option in primary care for patients with long COVID experiencing fatigue and/or respiratory symptoms.

TRIAL REGISTRATION NUMBER: NCT05244044.},
}

Humans
Male
Female
Middle Aged
*COVID-19/rehabilitation/physiopathology/complications
*Exercise Tolerance/physiology
Primary Health Care
Adult
Walk Test
SARS-CoV-2
*Exercise Therapy/methods
Aged
Hand Strength
Treatment Outcome
Fatigue
Dyspnea
Patient Reported Outcome Measures

@article {pmid41253056,
year = {2025},
author = {Ouyang, T and Huang, Z and Wei, S and Yang, J and Voskrebenzev, A and Vogel-Claussen, J and Guo, S and Yang, Q},
title = {Longitudinal assessment of pulmonary perfusion and ventilation defects in long COVID: A one-year study using phase-resolved functional lung (PREFUL) MRI.},
journal = {Computers in biology and medicine},
volume = {199},
number = {},
pages = {111316},
doi = {10.1016/j.compbiomed.2025.111316},
pmid = {41253056},
issn = {1879-0534},
abstract = {RATIONALE AND OBJECTIVES: The long-term trajectories of pulmonary perfusion and ventilation after recovery from SARS-CoV-2 infection are lacking. This study aims to longitudinally assess changes in perfusion (QDP) and ventilation (VDP) defects using phase-resolved functional lung (PREFUL) MRI in post-SARS-CoV-2 infection.

MATERIALS AND METHODS: This prospective study was conducted from January to May 2023 and included non-hospitalized, COVID-19-positive patients with pneumonia or symptoms suggestive of pneumonia, as well as healthy controls. Serial MRI scans were performed at acute, 3, 6, and 12 months after symptom onset, and healthy controls underwent only one MRI scan. Longitudinal comparisons of QDP and VDPCombined were employed by linear mixed-effects models. Long COVID was defined as persistent SARS-CoV-2 symptoms for at least three months, with associated factors identified through logistic regression.

RESULTS: A total of 60 participants (median age 68.5 years; 30 female) were included. VDPCombined was 21 %, 18 %, 16 %, and 13 % at the acute phase, 3 months, 6 months, and 12 months, respectively, with a significant difference observed in the longitudinal comparison (P = 0.034). Moreover, at 12 months, VDPCombined showed no significant difference compared to the healthy control (P = 0.280). QDP also decreased (42 %, 36 %, 35 %, and 19 % at acute, 3 months, 6 months, and 12 months, respectively; P < 0.001), but remained significantly higher than in healthy controls at 12 months (P < 0.001). At follow-up, 55 % of participants (33 of 60) had long COVID, with higher acute-phase QDP associated with increased odds of developing long COVID (odds ratio, 1.20; P = 0.001).

CONCLUSION: Pulmonary perfusion impairment persists up to 12 months following SARS-CoV-2 infection. Severe perfusion defects during acute phase are a risk factor for the development of long COVID.},
}

@article {pmid41252855,
year = {2025},
author = {Oh, S and Wijaya, J},
title = {Predictive surveillance and diagnosis of COVID-19: An integrative machine learning and wastewater multi-omics approach.},
journal = {Water research},
volume = {289},
number = {Pt B},
pages = {124981},
doi = {10.1016/j.watres.2025.124981},
pmid = {41252855},
issn = {1879-2448},
abstract = {COVID-19 has had major global impacts, highlighting the importance of robust predictive surveillance and diagnostic systems to ensure effective public health responses. Traditional surveillance methods based on passive case counting and diagnostic testing of individual patients often suffer from delays and resource constraints, preventing timely responses. This study proposed an integrative framework integrating machine learning (ML)-derived predictive surveillance with wastewater-based diagnosis, aiming to predict temporal trends in Korea and identify disease-causing agents. The ML model utilized crowdsourced COVID-19-related keywords, climatic, and environmental data, optimized via model selection and feature selection. The integrated data-driven model predicted COVID-19 cases over three years more accurately than those using single source data (i.e., baseline model). The explainable AI technique (i.e., helping to inform how the model made those predictive decisions) identified six keywords (reducing phlegm, throat pain, long COVID-19, sore throat, COVID-19 self-kit, and COVID-19 kit) as robust predictors of disease trends. In a proof-of-concept experiment, wastewater-based genotyping of disease-causing agents and affected human communities in sewershed areas was conducted. Metatranscriptomics of municipal wastewater was conducted to identify COVID-19 viral variants, evolutionarily related to those clinically isolated strains, distinguishable from conventional diagnostic testing of individual patients. Wastewater-derived metagenomics was also performed to assess genomic variation in the affected human populations. The integrative framework proposed in this study offers a rapid, cost-effective approach for the surveillance and diagnosis of COVID-19 and other infectious diseases, thus strengthening or complementing existing health systems.},
}

@article {pmid41249654,
year = {2025},
author = {Azola, A and Dastgheyb, RM and Easter, R and Parker, H and Della Penna, C and Santiuste, I and Schultz, H and Ehrenspeck, A and Veenhuis, R and Rubin, LH},
title = {Putting the PASC Score to the Test: Clinical vs. Statistical Accuracy in Long COVID Diagnosis.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41249654},
issn = {1525-1497},
support = {RF1 MH133411/MH/NIMH NIH HHS/United States ; },
abstract = {OBJECTIVE: To validate the RECOVER Post-Acute Sequelae of SARS-CoV-2 infection (PASC) score in a cohort of patients who develop long COVID (LC) or fully recover while iteratively improving the tool's sensitivity and specificity.

METHODS: A cross-sectional study in 130 LC patients followed at LC clinics in Baltimore, MD, USA, who met the National Academies of Sciences, Engineering, and Medicine (NASEM) 2024 LC definition, and 60 SARS-CoV-2 exposed but fully recovered individuals. LC participants were required to have at least one neuropsychiatric symptom. Participants completed comprehensive surveys and questionnaires assessing symptoms based on published methods to determine PASC score. Using the NASEM 2024 LC definition as the "true" condition, we compared evaluation metrics for the RECOVER PASC score cutoff (PASC > 12) and the presence of individual/multiple symptoms. Evaluation metrics (e.g., sensitivity, specificity, F1) were calculated based on these classifications for the overall PASC score and symptom combinations.

RESULTS: The LC cohort (n = 130) had a mean age of 47.2 years and was predominantly female (72%), White (79%), and well-educated (77% > 16 years). Controls (n = 60) were similar demographically. LC diagnosis and PASC scores were significantly associated (χ[2] = 102.99, P < 0.001). The PASC score showed excellent specificity (100%) and positive predictive value (PPV; 100%) albeit limited sensitivity (80%), missing 20% of participants with LC. We found that loss of smell/taste, post-exertional malaise, or lack of sexual desire or capacity demonstrated 94% sensitivity, 92% specificity, and 96% PPV, 87% NPV, and an F1 score of 0.949.

CONCLUSION: Validation of the RECOVER PASC supports its utility and highlights the need for ongoing refinement of the LC definition. We call for national efforts to develop readily implementable clinical tools for LC diagnosis.},
}

@article {pmid41249484,
year = {2025},
author = {Eisinger, RW and Breen, JJ and Beigel, J and Geerling, E and Gerberding, J and Taubenberger, JK},
title = {Progress on the pathway to long COVID treatments.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {41249484},
issn = {1529-2916},
}

@article {pmid41249167,
year = {2025},
author = {Thaweethai, T and Donohue, SE and Martin, JN and Hornig, M and Mosier, JM and Shinnick, DJ and Ashktorab, H and Atieh, O and Blomkalns, A and Brim, H and Chen, Y and Cortez, MM and Erdmann, NB and Flaherman, V and Goepfert, P and Goldman, JD and Hamburg, NM and Han, JE and Heath, JR and Jacoby, V and Jolley, SE and Kelly, JD and Kelly, SW and Kim, C and Krishnan, JA and Letts, R and Levitan, EB and Modes, ME and McComsey, GA and Metz, TD and Mullington, JM and Ofotokun, I and Okumura, MJ and Paredes, CC and Patterson, TF and Peluso, MJ and Reece, R and Sherif, ZA and Simhan, HN and Simmons, C and Singh, U and Taylor, BS and Taylor, BD and Trinity, JD and Troxel, AB and Utz, PJ and Vasey, AJ and Weinberger, E and Wiley, Z and Wisnivesky, J and Yee, LM and Horwitz, L and Foulkes, AS and Levy, BD and , },
title = {Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9557},
pmid = {41249167},
issn = {2041-1723},
support = {OTA OT2HL161841, OT2HL161847, OT2HL156812, OT2HL162087, and R01 HL162373//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
mesh = {Humans ; *COVID-19/epidemiology/physiopathology/virology ; Female ; Male ; United States/epidemiology ; Adult ; Middle Aged ; Prospective Studies ; SARS-CoV-2 ; Longitudinal Studies ; Aged ; Post-Acute COVID-19 Syndrome ; },
abstract = {Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition. Long COVID trajectories were determined prospectively among 3,659 participants (69% female; 99.6% Omicron era) in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort. Finite mixture modeling was used to identify distinct longitudinal profiles based on a Long COVID research index measured 3 to 15 months after infection. Eight longitudinal profiles were identified. Overall, 195 (5%) had persistently high Long COVID symptom burden, 443 (12%) had non-resolving, intermittently high symptom burden, and 526 (14%) did not meet criteria for Long COVID at 3 months but had increasing symptoms by 15 months, suggestive of distinct pathophysiologic features. At 3 months, 377 (10%) met the research index threshold for Long COVID. Of these, 175 (46%) had persistent Long COVID, 132 (35%) had moderate symptoms, and 70 (19%) appeared to recover. Identification of these Long COVID symptom trajectories is critically important for targeting enrollment for future studies of pathophysiologic mechanisms, preventive strategies, clinical trials and treatments.},
}

Humans
*COVID-19/epidemiology/physiopathology/virology
Female
Male
United States/epidemiology
Adult
Middle Aged
Prospective Studies
SARS-CoV-2
Longitudinal Studies
Aged
Post-Acute COVID-19 Syndrome

@article {pmid41248356,
year = {2025},
author = {Nejatinamini, S and Charlton, C and Harman, S and Kanji, JN and Kellner, JD and Lines, K and Murdoch, K and Powell, W and Roberts, J and Rosner, W and Shen-Tu, G and Tipples, G and Xu, JY and Vena, JE},
title = {COVID-19 antibody testing study: a nested substudy within Alberta's Tomorrow Project (ATP) in Alberta, Canada.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e101336},
doi = {10.1136/bmjopen-2025-101336},
pmid = {41248356},
issn = {2044-6055},
mesh = {Humans ; Alberta/epidemiology ; Middle Aged ; *COVID-19/epidemiology/diagnosis/immunology ; Female ; Male ; Adult ; Aged ; Prospective Studies ; *SARS-CoV-2/immunology ; *Antibodies, Viral/blood ; *COVID-19 Serological Testing ; Longitudinal Studies ; },
abstract = {PURPOSE: The Alberta's Tomorrow Project (ATP) prospective cohort study was established in 2000 to investigate the causes of cancer and chronic disease. The cohort consists of almost 55 000 participants aged 35-69 years at the time of recruitment. From 2020 to 2022, ATP conducted a longitudinal substudy, the COVID-19 Antibody Testing (CAT) study, nested in this existing cohort, to understand the spread and impact of the SARS-CoV-2. In this cohort profile, we describe the CAT study design, recruitment and initial findings.

PARTICIPANTS: In this prospective cohort substudy, ~4000 participants completed online surveys and provided blood samples at a study centre every 4 months for 1 year, across four cities in Alberta, Canada. The study was launched on a rolling basis beginning in September 2020 and data collection was completed in May 2022. The surveys collected information on health and lifestyle factors, COVID-19 (testing, symptoms, vaccination, public health recommendations) and impacts of the pandemic (including economic, health services, mental health). Blood samples were tested for antinucleocapsid and antispike protein SARS-CoV-2 antibodies.

FINDINGS TO DATE: A total of 4102 participants consented and attended a study centre at baseline, and almost 90% of these completed the study. Overall, participants were aged 61±10 years, 60% female, 12% came from rural areas, 45% had at least a bachelor's degree, 24% reported a household income <$C75 000 and 39% were retired. About 15% of participants tested positive for antibodies induced by a SARS-CoV-2 infection over the course of the study, and about 18% of those who were infected reported long COVID (persistent symptoms for >4 weeks). By the end of the study, 96% of participants had received at least one COVID-19 vaccine dose. Through investigating other outcomes, it was observed that participants under 50 years of age were more likely to be assessed to have mild or moderate-to-severe anxiety and depressive symptoms compared with older participants. In addition, approximately 15% of participants reported a moderate to major impact on their ability to meet financial obligations.

FUTURE PLANS: Serology results, together with health, lifestyle and sociodemographic data, and the continued follow-up of these participants as part of the broader ATP cohort study (planned through 2065), will provide opportunities to investigate the long-term sequelae of COVID-19 infection as well as the broader impacts of the pandemic on physical, mental and emotional health. Data are available to researchers on request through the ATP access process.},
}

Humans
Alberta/epidemiology
Middle Aged
*COVID-19/epidemiology/diagnosis/immunology
Female
Male
Adult
Aged
Prospective Studies
*SARS-CoV-2/immunology
*Antibodies, Viral/blood
*COVID-19 Serological Testing
Longitudinal Studies

@article {pmid41248018,
year = {2025},
author = {Wu, J and Xie, N and Meng, W and Ma, Y and Li, Z and Zeng, H and Chen, Y},
title = {Long COVID and symptom persistence in post-discharge omicron patients: Insights into C-reactive protein.},
journal = {Chronic illness},
volume = {},
number = {},
pages = {17423953251387913},
doi = {10.1177/17423953251387913},
pmid = {41248018},
issn = {1745-9206},
abstract = {ObjectivesLong-term health effects of Omicron infection, particularly persistent Long COVID in hospitalized patients, require further investigation.MethodsPatients hospitalized for Omicron infection (Dec 2022-Mar 2023) underwent follow-ups at 6 months and 1 year post-discharge. Univariate/multivariate analyses identified mortality predictors, symptom trends, and optimal CRP levels (mg/L) thresholds.ResultsAmong 410 patients, 59 died; mortality predictors included age (OR = 1.070), ICU admission (OR = 15.748), diabetes (OR = 3.363), antibacterial use (OR = 0.283), and lymphocyte count (OR = 0.099). At 6 months, 86.0% reported ≥1 symptom (83.5% at 1 year). Fatigue, cough, and snoring were most common, with symptom counts decreasing significantly over time. Symptomatic patients had longer hospital stays (P = 0.022), lymphopenia (P = 0.036), and elevated CRP levels (P = 0.010). A CRP level ≥15.38 mg/L was associated with a greater risk of symptom persistence and may serve as a potential predictive marker.ConclusionHospitalized Omicron survivors experience prolonged symptoms, with ICU admission, age, and diabetes as key mortality risks. Fatigue and snoring may persist despite overall improvement. Elevated CRP and prolonged hospitalization in symptomatic patients underscore the need for long-term monitoring and interventions targeting high-risk groups.},
}

@article {pmid41247781,
year = {2025},
author = {Henrich, TJ and Montgomery, CP and Graf, J and Ismali, N and Mohandas, S and Suthar, MS and Brim, H and Coffin, JM and Pagaria, A and Guzmán Rivera, J and Vudali, U and Keim, P and Zhong, G and McGrath, R and Edwards, B and García-Sastre, A and Gennaro, ML},
title = {The role of co-infection in the pathogenesis of acute SARS-CoV-2 infection and development of post-acute sequelae: A perspective.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
doi = {10.7554/eLife.106308},
pmid = {41247781},
issn = {2050-084X},
mesh = {Humans ; *COVID-19/complications/pathology/virology ; *Coinfection/virology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Bacterial Infections/complications ; },
abstract = {A major health challenge resulting from the COVID-19 pandemic is the manifestation of post-acute sequelae of SARS-CoV-2 (PASC). PASC (or long COVID) is a collective term used for clinical symptoms, various pathologies, and life-quality-changing functional impairment that persist for months to years after the initial SARS-CoV-2 infection. The mechanisms underlying PASC are not understood, although advances have been made in identifying factors that may contribute to long-term pathology. Recent data have emerged, showing an association between SARS-CoV-2 viral persistence and non-SARS-CoV-2 infections (pre-existing, viral reactivation, or new infections) in facilitating or mediating PASC. However, the heterogeneous nature and timing of co-infections have made it challenging to understand, interpret, and contextualize their contribution to PASC. Here, we summarize the impact of potential viral, bacterial, and fungal infections on SARS-CoV-2 pathogenesis, with a focus on their possible roles in the development of PASC. We also provide a framework to understand the mechanisms of PASC and inform basic, translational, and clinical research initiatives, including RECOVER, a large and ongoing research initiative to understand, treat, and prevent long COVID.},
}

Humans
*COVID-19/complications/pathology/virology
*Coinfection/virology
*SARS-CoV-2
Post-Acute COVID-19 Syndrome
Bacterial Infections/complications

@article {pmid41245391,
year = {2025},
author = {Duarte, ACB and Lafetá, ML and Verrastro, CGY and Mancuso, FJ and Tanni, SE and Albuquerque, ALP and Sperandio, PA and Oliveira, RKF and Ota-Arakaki, JS and Ferreira, EVM},
title = {Chronic Dyspnea and Residual Pulmonary Vascular Sequelae After COVID-19 Pulmonary Embolism: A Retrospective Analysis.},
journal = {Pulmonary circulation},
volume = {15},
number = {4},
pages = {e70198},
doi = {10.1002/pul2.70198},
pmid = {41245391},
issn = {2045-8932},
abstract = {During the COVID-19 pandemic, Brazil was one of the most affected countries. Patients presented higher risk of acute venous thromboembolism (VTE), in particular, pulmonary embolism (PE). However, long-term implications of these events remain unknown. A retrospective analysis from the FENIX study was conducted, and patients with COVID-19-related VTE during hospitalization were included. Further analysis, up to 6 months after the acute event, was performed exclusively in patients with PE. Persistence of dyspnea and exercise intolerance was evaluated through imaging, rest, and exercise functional tests. Cumulative incidence of VTE during hospitalization among COVID-19 survivors followed at the outpatient clinic was 17.7% (n = 75/423) and of acute PE was 9.9% (n = 42/423). Patients with PE were mostly male (66%), 56 ± 16 years old, and mainly classified as intermediate-low risk (74%). Dyspnea (mMRC≥ 1) up to 6 months of PE was present in 56% (n = 19/34), with a borderline association with parenchymal lung sequelae on chest CT scan (p = 0.069). Symptomatic patients upon follow-up presented lower FEV1 and FVC, as well as increased peak VD/VT ratio and ventilatory inefficiency. No signs of pulmonary hypertension (PH) were identified on echocardiogram (ECHO) and cardiopulmonary exercise testing (CPET). Persistence of dyspnea among post-PE related to COVID-19 was high. However, no cases of PH were found; follow-up findings may be related to pulmonary parenchymal and microvascular injury. Also, we cannot exclude association with long-COVID, in which pathophysiological mechanisms are multifactorial, involving chronic inflammatory changes and multiorgan dysfunction, highlighting the need for comprehensive evaluation of exercise intolerance through invasive CPET.},
}

@article {pmid41245100,
year = {2025},
author = {Ramachandran, R and Sathar, F and Mokome, P and Mathabela, N and Mahlase, E and Charalambous, S and Rachow, A and Glover, NA and Ivanova, O},
title = {Acceptability and feasibility of a group intervention for long COVID in Johannesburg, South Africa: a mixed-method study.},
journal = {Frontiers in health services},
volume = {5},
number = {},
pages = {1666387},
doi = {10.3389/frhs.2025.1666387},
pmid = {41245100},
issn = {2813-0146},
abstract = {BACKGROUND: COVID-19 affected 777 million people globally, with 7.1 million deaths. In Africa, 9.6 million cases and 176,000 deaths were reported. Long COVID, a significant consequence of the COVID-19, presented by chronic symptoms, affects the physical and mental health, thereby impacting the quality of life. While high-income countries implemented rehabilitation programs for managing long COVID symptoms, low- and middle-income countries faced healthcare disparities. In South Africa, limited multidisciplinary interventions were evident. This study aimed to assess the acceptability and feasibility of an 8-week rehabilitation and self-management program for long COVID using mixed-methods approach in Johannesburg.

METHODS: Patients and hospital staff who suffered from at least one symptom of long COVID for a period of two months and who consented to participate in the intervention were recruited from Tembisa Provincial Tertiary Hospital. The recruitment was from July to October 2023. Questionnaires were administered and interviews with selected participants were conducted to assess the acceptability and feasibility of the intervention. A descriptive analysis was carried out for the quantitative data, and a deductive thematic analysis was used for the interviews.

RESULTS: The participants had positive perceptions towards the design of the intervention, delivery, materials used and support by research staff and external consultants such as dietitians, physiotherapists, and psychologists. The participants stated that the intervention had improved their knowledge of long COVID and increased their self-confidence. Major barriers related to the intervention perceived by the participants were infrastructure, time and language. Recommendations from the participants included expanding the intervention at the community level and extending the duration of the intervention beyond 8-weeks.

CONCLUSION: This pilot intervention, that aimed to manage the symptoms of long COVID, was well accepted by the participants and achieved its intended outcome. Similar interventions are required at the clinical as well as community levels.},
}

@article {pmid41244103,
year = {2025},
author = {Yue, Y and Han, X and Chen, Q and Dai, L and Ai, Q and Zhang, Z and Ma, F and Gao, J},
title = {The effect of pulmonary rehabilitation for post-acute sequelae of SARS-CoV-2 infection in patients: a systematic review and meta-analysis.},
journal = {Frontiers in rehabilitation sciences},
volume = {6},
number = {},
pages = {1634351},
doi = {10.3389/fresc.2025.1634351},
pmid = {41244103},
issn = {2673-6861},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, are characterized by persistent symptoms such as fatigue, dyspnea, and reduced functional capacity. Pulmonary rehabilitation (PR) is recommended for chronic respiratory conditions, but its effectiveness in PASC, particularly across different delivery modes, remains uncertain.

OBJECTIVE: To assess the impact of PR, including telerehabilitation and in-person modalities, on physical function, dyspnea, pulmonary function, fatigue, and quality of life in patients with PASC.

METHODS: We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science from inception to March 25 for controlled clinical trials assessing the effects of PR in PASC patients. Two independent reviewers performed study selection and data extraction. The risk of bias was assessed using the Cochrane Risk of Bias Tool, and data were analyzed using Review Manager (RevMan) 5.4.1. Effect sizes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI).

RESULTS: Ten randomized controlled trials involving 673 participants were included. Most studies were judged to have a moderate risk of bias. Compared with usual care, PR significantly improved six-minute walk distance (MD: 76.85 meters; 95% CI: 57.35-96.36; p < 0.001), maximal inspiratory pressure (MD: 17.63 cmH₂O; 95% CI: 4.50-30.76; p = 0.009), fatigue (SMD: -1.15; 95% CI: -1.83 to -0.48; p < 0.001), and quality of life (SMD: 1.73; 95% CI: 0.56-2.91; p = 0.004). No statistically significant improvement was found for dyspnea (MD: -0.41; 95% CI: -1.51 to -0.68; p = 0.46). Subgroup analyses showed no significant differences between telerehabilitation and in-person PR across all outcomes, including exercise capacity (p = 0.84), dyspnea (p = 0.86), fatigue (p = 0.93), and quality of life (p = 0.44).

CONCLUSIONS: PR improves physical and functional outcomes in patients with PASC. Telerehabilitation offers a clinically equivalent alternative to in-person PR, supporting its broader implementation.},
}

@article {pmid41242093,
year = {2025},
author = {Alonso-Domínguez, J and González-Nóvoa, JA and López-López, A and Martínez-Barros, I and Pérez-González, A and Leiro-Fernández, V and Aguayo-Arjona, J and Teijeira, S and Veiga, C and Poveda, E},
title = {Artificial intelligence-based identification of key risk factors for long COVID from early clinical data.},
journal = {Journal of infection and public health},
volume = {19},
number = {1},
pages = {103051},
doi = {10.1016/j.jiph.2025.103051},
pmid = {41242093},
issn = {1876-035X},
abstract = {INTRODUCTION: Long COVID, a complex condition characterized by persistent symptoms following SARS-CoV-2 infection, has become a significant public health concern. Early identification of individuals at risk for long COVID is crucial for effective management. This study explores the potential of biochemical and clinical markers, alongside machine learning (ML) models, to predict long COVID development using data from the first 72 h post-admission.

METHODS: We analyzed clinical and laboratory data from 394 individuals diagnosed with SARS-CoV-2. A predictive model for long COVID was developed using machine learning algorithms, particularly XGBoost, to identify key biomarkers associated with the development of long COVID symptoms at 3 months post-infection. The model hyperparameters were optimized using Bayesian optimization techniques, and variable importance was assessed using SHAP values.

RESULTS: The predictive model achieved an area under the receiver operating characteristic curve (AUC-ROC) of 0.732, indicating moderate discriminatory power. Key variables identified included hemoglobin levels, oxygen saturation, weight, C-reactive protein (CRP), activated partial thromboplastin time (APTT), sodium, type of pulmonary infiltrates, and sex. Hemoglobin levels were the only statistically significant variable (p = 0.015) between those who developed long COVID and those who did not. Despite these findings, the model showed moderate overall accuracy (63.9 %) but excelled in recall (78.6 %), highlighting its potential in clinical settings for early identification of high-risk patients.

CONCLUSIONS: Our study demonstrates the feasibility of using machine learning to predict long COVID based on early clinical and laboratory data. While individual biomarkers alone may have limited predictive value, their combination enhances risk assessment for long COVID. Future studies should focus on refining the model and validating it in broader populations, including those with milder COVID-19 forms, to improve its accuracy and clinical utility.},
}

@article {pmid41241149,
year = {2025},
author = {Park, WH},
title = {The Mitochondrial Nexus: Dysfunction, Inhibition, and Therapeutic Frontiers in Lung Disease.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108506},
doi = {10.1016/j.rmed.2025.108506},
pmid = {41241149},
issn = {1532-3064},
abstract = {Mitochondria are increasingly recognized as central arbiters of cellular fate, placing them at the nexus of pulmonary health and disease. Beyond their canonical role in adenosine triphosphate (ATP) synthesis, these organelles are critical hubs for redox signaling, metabolic homeostasis, and programmed cell death. Mitochondrial dysfunction-a multifaceted condition characterized by impaired bioenergetics, excessive reactive oxygen species (ROS) production, aberrant dynamics, and defective quality control via mitophagy-is a unifying pathogenic feature in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary arterial hypertension (PAH). This dysfunction is also a critical determinant of severity in acute conditions like acute lung injury (ALI) and COVID-19 and is a key mechanistic driver of Long COVID. This review synthesizes the core mechanisms of mitochondrial impairment, delineates their specific contributions to this spectrum of pulmonary pathologies, and discusses the burgeoning field of mitochondria-targeted therapeutics. Strategies ranging from targeted antioxidants and metabolic modulators to novel regenerative approaches like mitochondrial transplantation are highlighted, with an expanded discussion on their limitations, challenges, and clinical implications. By framing mitochondrial integrity as a critical determinant of pulmonary disease, we underscore a pivotal axis for future diagnostic and therapeutic innovation.},
}

@article {pmid41239971,
year = {2025},
author = {Sun, H and Mullington, JM and Thomas, RJ},
title = {Post-Infection Sleep Syndrome: Long COVID as an Example.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsaf366},
pmid = {41239971},
issn = {1550-9109},
}

@article {pmid41239762,
year = {2025},
author = {Covre, ER and Laranjeira, C and Carreira, L and Höring, CF and Góes, HLF and Baldissera, VDA and Marques, PG and Meireles, VC and Tostes, MFDP and Oliveira, RR and Paiano, M and Ageno, RS and Moroskoski, M and Alcaraz, JP and Vissoci, JN and Facchini, LA and Salci, MA},
title = {Prevalence and Predictors of Long Covid in a Cohort of Brazilian Adults 12 Months After Acute Infection: A Cross-Sectional Study.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {6},
pages = {e70467},
pmid = {41239762},
issn = {1369-7625},
support = {//This study was funded by Ministério da Ciência, Tecnologia, Inovações e Comunicações (FNDCT/MCTIC), Ministério da Saúde (MS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-Processo n◦ 402882/2020-2. It was also supported by FCT-Fundação para a Ciência e a Tecnologia, I.P. (UID/05704/2023) and by the Scientific Employment Stimulus-Institutional Call-[https://doi.org/10.54499/CEECINST/00051/2018/CP1566/CT0012, accessed on 20 September 2025]./ ; },
mesh = {Humans ; Brazil/epidemiology ; Cross-Sectional Studies ; Female ; *COVID-19/epidemiology ; Middle Aged ; Male ; Prevalence ; Adult ; Aged ; SARS-CoV-2 ; Risk Factors ; Post-Acute COVID-19 Syndrome ; Young Adult ; Severity of Illness Index ; },
abstract = {INTRODUCTION: Since the onset of the pandemic in early 2020, various reports have emerged regarding persistent symptoms associated with Covid-19. Nevertheless, there is insufficient data on the persistence of symptoms over time. This study sought to estimate the prevalence of persistent symptoms 12 months after Covid-19 infection and identify predictors of long Covid in adults living in the State of Paraná, southern Brazil, according to the level of severity of Covid-19 infection.

METHOD: An observational and cross-sectional survey was conducted with Brazilian adults diagnosed with Covid-19, as assessed from data available in two official Covid-19 notification databases in Brazil, using telephone interviews. Descriptive statistics, tests of associations and simple and multiple binary logistic regression analysis were used to identify predictors of long Covid.

RESULTS: In total, 1033 adults participated in the study. The overall prevalence of long Covid was 60.3% (n = 623). Prevalence was higher in women (67.7%), people aged between 50 and 59 years (65.8%) and in individuals who received treatment in an Intensive Care Unit (ICU) during the acute phase of Covid-19 infection (74.4%, n = 241). The risk factors associated with a greater chance of developing long Covid were: female (OR 2.38; 95% CI 1.55; 3.66), living in the Brazilian northwest health macro-region (OR 2.20; 95% CI 1.21; 4.00), presenting multimorbidity (OR 1.86; 95% CI 1.06; 3.28), having an average of six symptoms in the acute phase of Covid-19 (OR 1.22; 95% CI 1.17; 1.28) and having received treatment in an ICU (OR 4.86; 95% CI 2.83; 8.35) and inpatient ward (OR 2.45; 95% CI 1.47; 4.09).

CONCLUSIONS: The results highlight the high prevalence of long Covid and support the formulation of health policies capable of minimising the consequences on the population, on the services offered by professionals and on health systems.

The study topic's importance was based on the patients' experiences in the author's previous research and the need to develop patient-centred care.},
}

Humans
Brazil/epidemiology
Cross-Sectional Studies
Female
*COVID-19/epidemiology
Middle Aged
Male
Prevalence
Adult
Aged
SARS-CoV-2
Risk Factors
Post-Acute COVID-19 Syndrome
Young Adult
Severity of Illness Index

@article {pmid41239370,
year = {2025},
author = {Lindblom, S and Lindberg, P and Ljunggren, G and Lee, S and Kisiel, MA and Kolosenko, I and Petrovic, P and Sklivanioti Greenfield, M and Wachtler, C and Fedorowski, A and Wheelock, ÅM and Carlsson, AC},
title = {Prevalence of depression, anxiety, fatigue, and headache before and after long COVID onset: a case-control study in the total population of Region Stockholm.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {633},
pmid = {41239370},
issn = {1741-7015},
support = {M23-01339//Åke Wiberg Stiftelsen/ ; HLF20210053//The Swedish Heart-lung foundation/ ; 2021-06546//The Swedish Research Council/ ; FoUI-97300//Region Stockholm/ ; },
mesh = {Humans ; Male ; Female ; Sweden/epidemiology ; *COVID-19/epidemiology/psychology/complications ; *Fatigue/epidemiology/etiology ; *Headache/epidemiology/etiology ; Case-Control Studies ; Middle Aged ; *Anxiety/epidemiology ; *Depression/epidemiology ; Prevalence ; Adult ; Aged ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection, or long COVID, include diverse symptoms and remain a major concern worldwide. This study investigates the occurrence of depression, anxiety, fatigue, and headache 1 year prior to the COVID-19 pandemic (2019), 12 months prior to, and 6 months after long COVID diagnosis in individuals diagnosed with long COVID and matched population-based controls.

METHODS: This case-control study included nonhospitalized individuals diagnosed with long COVID compared with controls without long COVID, matched by age, sex, and neighborhood socioeconomic status. Data were collected from the Stockholm Regional Health Care Data Warehouse (VAL), including diagnoses in 2019, 12 months before, and 6 months after the long COVID diagnosis. Conditional logistic regression was used to calculate odds (OR) ratios and 99% confidence intervals (CI).

RESULTS: A total of 5589 cases (mean age: 47 years, 69% female) and 47,561 controls were included. Individuals with long COVID had a higher pre-pandemic frequency of the following diagnoses: depression (women: OR 1.57 (1.26-1.97), men: OR 1.40 (0.88-2.23)), anxiety (women: OR 1.65 (1.41-1.93), men: OR 2.10 (1.56-2.84)), fatigue syndrome after viral infection (women: OR 1.96 (0.86-4.48), men: OR 2.22 (0.29-17)), and headache (women: OR 2.45 (1.96-3.05), men: OR 2.89 (1.86-4.50)). Individuals with long COVID also had a higher frequency of these diagnoses 12 months before and 6 months after the long COVID diagnosis was made, regardless of sex.

CONCLUSIONS: Individuals with long COVID had a higher prevalence of depression, anxiety, fatigue, and headache both before and after being diagnosed with long COVID compared with controls without long COVID. The findings suggest an association between mental health vulnerabilities and long COVID, while the frequency of registered mental health diagnoses remained largely similar after the long COVID diagnosis.},
}

Humans
Male
Female
Sweden/epidemiology
*COVID-19/epidemiology/psychology/complications
*Fatigue/epidemiology/etiology
*Headache/epidemiology/etiology
Case-Control Studies
Middle Aged
*Anxiety/epidemiology
*Depression/epidemiology
Prevalence
Adult
Aged
Post-Acute COVID-19 Syndrome
SARS-CoV-2

@article {pmid41239121,
year = {2025},
author = {Villasis, NA and Santos, JJ and Ettner, SL and Xu, H and Escarce, JJ and Leung, LB},
title = {Long COVID Disproportionately Reported by Disadvantaged Individuals: A National Survey of U.S. Working-Age Adults.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-025-09912-w},
pmid = {41239121},
issn = {1525-1497},
support = {1RF1MH133436-01/MH/NIMH NIH HHS/United States ; IK2 HX002867/HX/HSRD VA/United States ; },
abstract = {BACKGROUND: COVID-19 disproportionately affects racial/ethnic minorities and economically disadvantaged persons, which may also apply to sequelae from acute infection. Little is known about those who live with post-acute sequelae of SARS-CoV-2 infection (PASC), including long COVID, especially those without a formal diagnosis.

OBJECTIVE: To examine self-reported long COVID symptoms and its associations with individual and state characteristics from a national survey sample of working-age adults.

DESIGN: Repeated cross-sectional survey analysis.

PARTICIPANTS: Eighteen- to 64-year-old adults who reported ever having had COVID-19 (n = 409,087).

MAIN MEASURES: We examined long COVID responses from the online Household Pulse Survey (9/22/2022-10/30/2023), administered by the Census Bureau and the National Center for Health Statistics. Long COVID was defined as having "symptoms lasting 3 months or longer that you did not have prior to having coronavirus" (e.g., fatigue, difficulty thinking, shortness of breath) or not. Logistic regression models adjusted for survey week, respondent characteristics (e.g., demographics, acute COVID-19 severity), and state characteristics (e.g., rurality, Health Professional Shortage Areas). We additionally examined concurrent depression and anxiety symptoms.

KEY RESULTS: The HPS response rate was 6.10% during the study timeframe.[14] Among those who ever had COVID-19, 27.5% reported long COVID symptoms. Among those with long COVID symptoms, 22.6% reported having severe activity limitations. In fully adjusted models, long COVID symptoms were most commonly reported by Hispanic respondents (ΔPH = 2.3, SE = 0.7), among all racial-ethnic groups. Low socioeconomic status was consistently associated with long COVID symptoms: Income (ΔP<25k vs >=200k+ = 11.9, SE = 0.9); Medicaid-insurance (ΔPMedicaid v Employer-sponsored = 02.9, SE = 0.5); Uninsurance (ΔPUninsured v Employer-sponsored = 1.8, SE = 0.4). Long COVID symptoms were associated with living in more rural states (ΔP = 0.08, SE = 0.02). Long COVID symptoms were additionally associated with concurrent anxiety (ΔPAnx v Not = 8.0, SE = 0.4) and depressive symptoms (ΔPDep v Not = 6.7, SE = 0.6).

CONCLUSIONS: Long COVID symptoms and disability were disproportionately reported among survey respondents who were Hispanic and who were economically-disadvantaged. Rural communities were more so impacted.},
}

@article {pmid41238605,
year = {2025},
author = {Toyokura, E and Yamada, K and Asai, K and Tsutsumi, M and Ueda, T and Hirai, K and Furukawa, Y and Miyamoto, A and Nishimura, M and Sato, K and Watanabe, T and Tabuchi, T and Kawaguchi, T},
title = {Dual use of combustible and heated tobacco products associates persistent symptoms with a history of COVID-19: a JASTIS 2023 cross‑sectional study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {38659},
pmid = {41238605},
issn = {2045-2322},
support = {JP23K07631//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; *COVID-19/epidemiology ; Middle Aged ; Adult ; SARS-CoV-2 ; *Tobacco Products/adverse effects ; Aged ; Risk Factors ; Dyspnea/etiology/epidemiology ; Cigarette Smoking/adverse effects ; },
abstract = {Multiple reports have identified smoking as a risk factor for long COVID; however, few have distinguished among tobacco product types. We conducted a cross-sectional study using data from an internet-based survey administered in February 2023 to examine the association between 12 persistent symptoms and smoking status in participants with a history of COVID-19. A total of 28,250 participants were included, of whom 5,068 had a history of COVID-19. Among current tobacco users with a history of COVID-19, the odds ratios for persistent symptoms were significantly elevated for four symptoms-arthralgia, chest pain, dyspnea, and dysosmia-compared to never smokers. For subgroup analysis, current tobacco users were categorized into three groups: combustible cigarette (CC), heated tobacco product (HTP), and dual users. Among dual users, the odds ratios were significantly elevated for five symptoms: arthralgia, chest pain, dyspnea, dysgeusia, and dysosmia. CC users showed significantly higher odds for chest pain, dyspnea, and fatigue, while HTP users for dyspnea and sexual dysfunction. Smoking in individuals with a history of COVID-19 associates the prevalence of persistent symptoms, and its impact may vary by smoking type. Separately analyzing smoking subgroups allows for a more accurate understanding of the relationship between persistent symptoms and smoking behavior.},
}

Humans
Male
Cross-Sectional Studies
Female
*COVID-19/epidemiology
Middle Aged
Adult
SARS-CoV-2
*Tobacco Products/adverse effects
Aged
Risk Factors
Dyspnea/etiology/epidemiology
Cigarette Smoking/adverse effects

@article {pmid41238390,
year = {2025},
author = {Waters, A},
title = {Long covid: Government failure to recognise disease as occupational is "unconscionable," say unions.},
journal = {BMJ (Clinical research ed.)},
volume = {391},
number = {},
pages = {r2407},
doi = {10.1136/bmj.r2407},
pmid = {41238390},
issn = {1756-1833},
}

@article {pmid41238086,
year = {2025},
author = {Yuan, RL and Wang, SS and Li, PY and Ruan, Y and He, JQ and Zhou, R and Wang, WF and Jiang, YT and Ye, JR and Peng, Y and He, WB and Chu, SF and Zhang, Z and Chen, NH},
title = {SARS-CoV-2 spike protein induces depressive-like behaviors by disrupting astrocytic Cx43-mediated gap junction intercellular communication.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106176},
doi = {10.1016/j.bbi.2025.106176},
pmid = {41238086},
issn = {1090-2139},
abstract = {BACKGROUND: Long COVID has emerged as a global health concern, with depression being one of its most debilitating and poorly understood manifestations. Despite evidence pointing to the role of neuroinflammation and astrocyte-mediated disruptions in brain function, the mechanistic details remain elusive.

METHODS: SARS-CoV-2 spike receptor-binding domain (RBD) was microinjected into the medial prefrontal cortex (mPFC) to mimic cerebral infection, and the depressive-like behaviors, functional connectivity, and neuronal excitability were recorded for a 16-day period. Immunofluorescence, RNA sequencing, and ELISA were used to evaluate astrocytic gap junctions and inflammation. Gap junction intercellular communication (GJIC) dysfunction was confirmed by transfer of lucifer yellow (LY), cyclic adenosine monophosphate (cAMP), and cyclic GMP-AMP (cGAMP). We also investigated the role of Cx43 using conditional knockout mice, Gap 27-treated mice, and Cx43-knockdown astrocytes. Astrocytic Cx43 overexpression and celecoxib treatment were tested as a potential therapeutic to rescue Cx43 function.

RESULTS: Mice microinjected with RBD into the mPFC exhibited significant depressive-like behaviors, decreased neuronal excitability, and disrupted functional connectivity, accompanied by a marked reduction in astrocytic Cx43 expression and impaired GJIC. Functional assays, including Lucifer Yellow, cAMP, and cGAMP transfer, confirmed compromised gap junction activity, which was further associated with enhanced astrocytic type I interferon responses and cGAS-STING pathway activation. Conditional knockout of Cx43 in astrocytes or pharmacological inhibition of GJIC mimicked the depressive-like phenotypes induced by RBD. Importantly, Astrocytic Cx43 overexpression and celecoxib treatment restored Cx43 expression, improved GJIC, and effectively alleviated depressive-like behaviors in RBD-injected mice.

CONCLUSIONS: Astrocytic Cx43-mediated GJIC as a promising therapeutic strategy for managing depression in long COVID.},
}

@article {pmid41237918,
year = {2025},
author = {Aggarwal, A and Chanda, A},
title = {Effects of thoracic spinal manipulation in long COVID patients: A randomised controlled trial.},
journal = {Respiratory medicine},
volume = {250},
number = {},
pages = {108503},
doi = {10.1016/j.rmed.2025.108503},
pmid = {41237918},
issn = {1532-3064},
abstract = {INTRODUCTION: Long COVID patients manifest dyspnoea, chest heaviness, and symptoms, ascertaining deteriorated lung function. As thoracic spinal manipulation in such patients may lead to spinal misalignment, the chest wall compliance may also get affected. This study aimed to determine the role of thoracic spinal manipulation on pulmonary function, thoracic spine mobility, and chest expansion in patients with Long COVID.

METHODS: A Randomised Controlled trial was done in Dr. D.Y. Patil College of Physiotherapy, Pune, Maharashtra on 42 individuals who fulfilled the inclusion criteria. They were randomly assigned to two groups using the chit method. The experimental group (Group A), with a mean age of 23.85 ± 3.55 years (11 males, 10 females), underwent thoracic spinal manipulation in conjunction with pulmonary rehabilitation five times a week for two weeks. The control group (Group B) with a mean age of 24.9 (±5.26) years (9 males, 12 females) underwent pulmonary rehabilitation only. After two weeks, primary outcome measures, including pulmonary function, thoracic spine mobility, and chest expansion, were evaluated. The data were analysed with SPSS version 21 software using the Wilcoxon signed-rank and Mann-Whitney tests for within- and between-groups comparisons.

RESULTS: The experimental group showed a significant improvement (p < 0.05) in pulmonary function and thoracic spine mobility, except for thoracolumbar extension and chest expansion parameters versus control group. Within-group analysis of both groups, yielded significant results for all dependent outcome variables. (p < 0.05).

CONCLUSION: The study supports the role of thoracic spinal manipulation in improving pulmonary function and thoracic spine mobility in patients with Long COVID.},
}

@article {pmid41237491,
year = {2025},
author = {Staggs, H and Furst, A and Mills-Finnerty, C},
title = {Characterizing predictors and chronicity of brain fog in long COVID.},
journal = {Psychiatry research},
volume = {354},
number = {},
pages = {116813},
doi = {10.1016/j.psychres.2025.116813},
pmid = {41237491},
issn = {1872-7123},
abstract = {Long COVID is a chronic illness that persists following COVID-19 infection, with fatigue and brain fog as the most frequent complaints. However, there is no objective case definition for brain fog in long COVID and chronicity of symptoms remains unclear. This study recruited two waves of participants: those with a history of COVID-19, who participated in 2023 (N = 793, age = 38.5 ± 13.2, 44% female, 35.1% long COVID) and a follow up cohort collected in 2024 of participants who qualified as having long COVID at time point 1 (N=119, 61 female, 58 male). Participants completed questionnaires and cognitive tasks from home. We trained a binary classification model for long COVID diagnosis (73% accuracy) and a linear regression model for cognitive complaints (RMS error 5.8). A long COVID diagnosis at timepoint 1 was classified by biopsychosocial variables including stress, social support, and sex (women more likely). Symptom clustering revealed that phenotypes with both mental and physical health symptoms were predictive of brain fog, but not phenotypes with only sleep-related or physical symptoms. Markers of brain fog included slower reading and typing, slower reaction times in cognitive tasks, and changes in information processing speed and thresholds for making choices. Timepoint 2 data showed that the majority (82.4%) of participants did not remit from long COVID . These findings highlight the complex biopsychosocial factors that predict having long COVID with brain fog, and the need for interventions to improve remission rates.},
}

@article {pmid41237093,
year = {2025},
author = {, },
title = {Correction: Coping with stressful life disruptions due to long COVID: A qualitative study.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0336986},
pmid = {41237093},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0329831.].},
}

@article {pmid41235245,
year = {2025},
author = {Chen-Camaño, R and DeAntonio, R and López-Vergès, S},
title = {T-cell exhaustion in COVID-19: what do we know?.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1678149},
pmid = {41235245},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology ; *SARS-CoV-2/immunology ; *T-Lymphocytes/immunology ; T-Cell Exhaustion ; },
abstract = {T-cell exhaustion is a terminal state of immune dysfunction characterized by impaired proliferation and effector functions, diminished cytokine secretion, and sustained expression of inhibitory receptors. In coronavirus disease 2019 (COVID-19), increasing evidence links exhausted T-cell phenotypes with poor clinical outcomes, including severe disease, delayed viral clearance, and persistent symptoms associated with Long COVID. Exhaustion results from prolonged antigenic stimulation and inflammatory signals and is marked by transcriptional reprogramming, metabolic and epigenetic dysregulation, and co-expression of inhibitory receptors such as programmed cell death protein-1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Notably, exhausted phenotypes in COVID-19 frequently coexist with hyperactivation, raising the unresolved question of whether inhibitory receptor expression reflects transient activation or irreversible dysfunction. Emerging therapeutic strategies to reverse these dysfunctional states include immune checkpoint inhibitors, cytokine modulation, metabolic interventions, and epigenetic therapies, although their clinical translation remains at an early stage. Critical research gaps include the scarcity of longitudinal data, incomplete profiling of T-cell subsets across disease stages during COVID-19 and Long COVID-19, and contradictory evidence of vaccine-induced exhaustion with limited understanding of its consequences. This non-systematic literature review synthesizes current advances in COVID-19 immunopathology and therapeutic strategies, underscoring that understanding T-cell exhaustion is crucial to improving outcomes and shaping next-generation immunotherapies and vaccines.},
}

Humans
*COVID-19/immunology
*SARS-CoV-2/immunology
*T-Lymphocytes/immunology
T-Cell Exhaustion

@article {pmid41235244,
year = {2025},
author = {Wang, D and Zhang, F},
title = {CKD-related impairment in humoral and cellular immune response and potential correlation with long COVID-19: a systematic review.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1690298},
pmid = {41235244},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/prevention & control ; *Immunity, Humoral ; *Renal Insufficiency, Chronic/immunology/therapy ; *Immunity, Cellular ; *SARS-CoV-2/immunology ; *COVID-19 Vaccines/immunology ; Antibodies, Viral/blood/immunology ; Vaccination ; },
abstract = {INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of morbidity and mortality from SARS-CoV-2 infection (COVID-19). However, their immune response to vaccination may vary among individuals. The purpose of this review was to identify characteristics of alterations in humoral and cellular immune responses to the vaccination, and to provide insights into their immune dysfunctions for a better care of acute COVID-19 and prevention of long COVID-19.

METHODS: PubMed, Embase, Scopus, Web of science and Cochrane Central were systematically searched. Eligible publications included clinical studies reporting immune response to COVID-19 vaccination in CKD patients without dialysis or KT, CKD patients undergoing dialysis, as well as CKD patients with KT. Demographics, measurements and results of their humoral and cellular response were evaluated, and the quality of studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal tool and the Newcastle-Ottawa quality assessment scale (NOS).

RESULTS: A total of 31 eligible studies were identified. A decreased proportion of patients with KT showed anti-S IgG positivity after the 2[nd] (67%) and 3[rd] (56.6%) dose of vaccination. Similarly, a decreased proportion of these patients presented S-specific T-cell response after the 2[nd] (17.7%) and 3[rd] (12.9%) dose. Though lower anti-S IgG titers in patients with CKD or on dialysis, as well as T-cell response in patients on dialysis were reported to be lower after the 2[nd] or 3[rd] dose of vaccination, conflicting results were reported by other studies. Limited studies on correlated change between humoral and cellular immune response revealed a low rate of co-presence of the two in patients with dialysis, though antibody level was correlated with rate of cellular response, while no such correlation was revealed in patients with KT.

CONCLUSION: The study provides crucial information on features of humoral and cellular immune responses to COVID-19 vaccinations in CKD patients, and suggests possible directions for strategy of management such as antibody monitoring, additional booster dose or immunomodulatory therapies not only for acute COVID-19 but also for long COVID-19.},
}

Humans
*COVID-19/immunology/prevention & control
*Immunity, Humoral
*Renal Insufficiency, Chronic/immunology/therapy
*Immunity, Cellular
*SARS-CoV-2/immunology
*COVID-19 Vaccines/immunology
Antibodies, Viral/blood/immunology
Vaccination

@article {pmid41232803,
year = {2025},
author = {Brand, O and Kirkham, S and Jagger, C and Ozols, M and Purohit, K and Zhang, Z and Lennon, R and Hussell, T and Eckersley, A},
title = {Lung basement membranes are compositionally and structurally altered following resolution of influenza infection.},
journal = {Mucosal immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mucimm.2025.11.005},
pmid = {41232803},
issn = {1935-3456},
abstract = {Identification of pathways preventing timely recovery from acute respiratory viral infection is under-studied but essential for long-term health. Using unbiased proteomics, we reveal an unexpected, reduction in lung basement membrane proteins 21 days after influenza infection when mice had symptomatically recovered. Basement membrane provides a critical scaffold for heterogeneous cell types and the proteins they secrete/express at the endothelial and epithelial barrier. Further peptide location fingerprinting analysis shows inherent structure-associated changes within core collagen IV and laminin components, particularly within the NC1 domains of collagen IV. Our results imply lingering damage to the basement membrane network despite symptomatic recovery from viral infection. Surprisingly, similar structure-associated changes in laminin and collagen IV components are also observed in non-infected, aged mice indicating that inflammation-driven basement membrane degeneration may contribute to tissue ageing. Interestingly, macrophages in regions deficient in basement membrane express collagen IV and laminin chains. Repair of the basement membrane should therefore be targeted to improve overall lung health. Non-technical summary: Lung virus infection is a constant global threat, despite developments in vaccination and anti-viral treatments. We have a deep understanding of this inflammatory condition but less is known about the drivers of persistent problems, including fatigue and breathlessness as illustrated by "long COVID". Here, we reveal a novel finding that a critical structure in the lung (the basement membrane) remains damaged after the influenza virus and symptoms have cleared. This structure supports a variety of cells and forms a barrier that lines the airspaces. It also regulates fluid and cell movement into these airspaces. Remarkably, we show that similar changes after virus infection are also evident in aged lungs, which implies that lung complications with age may be due to repeated inflammation. By identifying these persistent basement membrane changes, we provide an entirely novel area to target with new medicines to treat complications arising from viral infection.},
}

@article {pmid41232748,
year = {2025},
author = {Silva, CAC and Bomfim, AP and Medeiros, JD and Silva, JJ and Cazé-Ceron, AB and Cerqueira-Silva, T and Khouri, R and Barral, A and Barral-Netto, M and Fernandes, GDR and Barbosa, CG and Boaventura, VS},
title = {Nasal Microbiota and Clinical Features in Acute Flu-Like Illness: COVID-19 Status and Long COVID Follow-Up.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108196},
doi = {10.1016/j.ijid.2025.108196},
pmid = {41232748},
issn = {1878-3511},
abstract = {OBJECTIVES: Long COVID (LC) is a challenging medical condition. Reliable diagnostic and targetable biomarkers of LC for a proper and early diagnosis and clinical care are an unmet medical need. Evaluate targetable biomarkers for LC management.

DESIGN: Comparison of nasal microbiota and clinical features in 291 individuals with acute influenzae-like illness (ILI), comparing COVID-19-positive (n=193) and negative (n=98) groups, with further stratification by long COVID (LC) outcomes (persistent symptoms >3 months).

RESULTS: Clinical characteristics were balanced across groups, with upper respiratory symptoms predominating. Individuals who developed LC exhibited more cardiorespiratory symptoms during acute infection (70% versus 48%, p=0.002). Nasal microbiota analysis revealed lower alpha diversity in COVID-19-positive individuals versus other ILI (Wilcoxon: Chao2 p=0.03305; Shannon p=0.02578; Simpson p=0.1082) but no differences in beta diversity or taxonomic composition between groups, including LC versus recovered individuals. EBV/CMV infection/reactivation was not associated with LC. Sensitivity analyses confirmed robustness to methodological and temporal biases.

CONCLUSIONS: Findings suggest acute nasal microbiota disruption in individuals with COVID-19, but no LC-specific microbial profile.},
}

@article {pmid41232201,
year = {2025},
author = {Nunes, M and Kruger, A and Fielding, B and Kell, DB and Pretorius, E},
title = {The effects of pseudoserum on thrombin-induced fibrin networks: Potential for clinical insight into coagulation independent of traditional parameters.},
journal = {Thrombosis research},
volume = {256},
number = {},
pages = {109530},
doi = {10.1016/j.thromres.2025.109530},
pmid = {41232201},
issn = {1879-2472},
abstract = {Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormones, metabolites, reactive oxygen species, acute phase reactants, and more. Here, we derive pseudoserum or clotting factor-depleted fractions from control, type II diabetes mellitus, and Long COVID platelet-poor plasma (PPP) samples, and expose them to purified, exogenous fibrinogen obtained from healthy donors. Thrombin-induced fibrin networks were then formed and visualized using light and scanning electron microscopy. The results demonstrate that pseudoserum can greatly influence the organization, density, and ultrastructure of fibrin networks formed from purified fibrinogen, emphasizing the role of non-clotting factors in fibrin formation. Fibrin networks formed from purified fibrinogen exposed to control pseudoserum appear homogeneous, exhibiting organised architecture with few regions of unusual density or aggregates, whereas the networks formed using patient pseudoserum show disorganisation, regions of density, fibre-like strands, and anomalous aggregates. These abnormalities are also observed in patient PPP samples, suggesting that fibrin network characteristics in PPP samples are also significantly influenced by non-clotting factors and are somewhat independent of endogenous fibrinogen. Furthermore, fibrinolysis was significantly reduced in the patient groups, demonstrating the ability of pseudoserum to influence the susceptibility of fibrin networks to plasmin-induced degradation. The ability of pseudoserum to drive these changes, despite the essential absence of endogenous fibrinogen and other classical clotting factors, suggests that soluble molecules retained in pseudoserum can directly modify fibrinogen's structural conformation and functionality, influence thrombin-mediated fibrin formation and polymerization, and/or impact Factor XIII's crosslinking capabilities. This study provides a systems-level perspective on the influence of pseudoserum on fibrin networks and highlights the potential of serum and other clotting factor-depleted fractions to yield deeper mechanistic and diagnostic insights into coagulation.},
}

@article {pmid41231196,
year = {2025},
author = {O'Connor, DB and Greenwood, DC and Mansoubi, M and Bakerly, ND and Bhatia, A and Collett, J and Davies, HE and Dawes, J and Delaney, BC and Ezekiel, L and Leveridge, P and Mir, G and Muehlhausen, W and Rayner, C and Scott, JT and Sivan, M and Tucker-Bell, I and Vashisht, H and Ward, T and Winch, D and Dawes, H and , },
title = {Daily stress and worry are additional triggers of symptom fluctuations in individuals living with Long COVID: results from an intensive longitudinal cohort study.},
journal = {Annals of behavioral medicine : a publication of the Society of Behavioral Medicine},
volume = {59},
number = {1},
pages = {},
pmid = {41231196},
issn = {1532-4796},
support = {//National Institute for Health and Care Research/ ; },
mesh = {Humans ; Male ; Female ; *COVID-19/psychology/complications/physiopathology ; *Stress, Psychological/psychology/complications ; Middle Aged ; Longitudinal Studies ; *Anxiety/psychology ; Aged ; Fatigue/psychology ; Adult ; *Depression/psychology ; *Rumination, Cognitive/physiology ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; United Kingdom ; Dizziness ; SARS-CoV-2 ; *Symptom Flare Up ; },
abstract = {BACKGROUND: Recent research has shown that exertion in physical, cognitive, social, and self-care activities triggers symptom severity in individuals with Long COVID.

PURPOSE: The current study aimed to investigate whether daily emotional exertions (stress, worry, rumination) were associated with symptom exacerbation, over and above influences of effortful daily activities, in individuals with Long COVID.

METHODS: In total, 376 participants were recruited from UK Long COVID clinics and community settings and completed daily assessments of activity and severity of 8 core symptoms every 3 hours for up to 24 days; 155 participants completed daily assessments of stress, worry, and rumination for at least 7 consecutive days.

RESULTS: Days with higher stress scores were associated with increased severity of all symptoms on the same day, after adjusting for activities, demographic and medical factors (P-values ≤ .007). Days with higher stress scores also predicted more severe anxiety and depression symptoms 1 day later (P < .001) and more severe anxiety (P < .001) and dizziness symptoms (P = .003) 2 days later. Days with higher worry scores were associated with increased fatigue (P < .001), anxiety (P < .001), depression (P < .001), and cognitive dysfunction (P = .002) on the same day, but decreased anxiety (P = .003) and depression (P = .002) symptoms 1 day later and less severe pain (P = .002) symptoms 2 days later. Daily rumination was only associated with 2 symptoms.

CONCLUSIONS: Daily stress and worry are distinct factors linked to fluctuations in same-day and next-day Long COVID symptoms, with daily stress showing the strongest association-consistent with patterns of postexertional symptom exacerbation. These findings highlight the importance of considering stress and worry as potential therapeutic targets and integrating their management into self-care programs.},
}

Humans
Male
Female
*COVID-19/psychology/complications/physiopathology
*Stress, Psychological/psychology/complications
Middle Aged
Longitudinal Studies
*Anxiety/psychology
Aged
Fatigue/psychology
Adult
*Depression/psychology
*Rumination, Cognitive/physiology
Severity of Illness Index
Post-Acute COVID-19 Syndrome
United Kingdom
Dizziness
SARS-CoV-2
*Symptom Flare Up

@article {pmid41231115,
year = {2025},
author = {Rai, KK and Gowman, H and Harrison, CS and Gruben, DC and Butfield, R and Hulme, R and Volkman, HR and Nguyen, JL and Yang, J},
title = {Understanding the role of COVID-19 vaccination in all-cause healthcare resource utilisation among adults with long covid in the Uk primary care setting: data from the 2022-2023 respiratory virus season.},
journal = {Expert review of vaccines},
volume = {},
number = {},
pages = {},
doi = {10.1080/14760584.2025.2589215},
pmid = {41231115},
issn = {1744-8395},
abstract = {BACKGROUND: The role COVID-19 vaccination on healthcare resource utilization (HCRU) and cost remains unclear, especially during Omicron predominance and among high risk UK populations.

RESEARCH DESIGN AND METHODS: A retrospective cohort study using UK The Health Improvement Network (THIN) primary care data included adults (≥18 years) with confirmed or suspected COVID-19 between September 2022- May 2023. Three cohorts were defined: Highest risk (eligible for two seasonal doses), High Risk (eligible for one dose), and All COVID-19 patients. Long COVID was identified as ≥ 1 symptom or diagnostic/referral code, ≥4 weeks post COVID-19 diagnosis. Inverse probability of treatment weighting assessed associations between vaccination status (yes/no and time since vaccination) and long COVID, HCRU, and costs.

RESULTS: In both Risk Cohorts, COVID-19 vaccination was not associated with long COVID incidence. However, in the High Risk (n = 1,889) and All Patients cohorts (n = 8,507) outpatient specialist referrals were significantly lower in the 3-6-month post-vaccination group versus > 6 months (rate ratio: 0.28; 95% CI: 0.10-0.79, p < 0.05 and 0.46; 95% CI: 0.27-0.79; p ≤ 0.01, respectively).

CONCLUSIONS: COVID-19 vaccination was not consistently associated with incidence of long COVID or all-cause HCRU. Findings suggest potential subgroup-specific benefits, highlighting the importance of annual vaccination. Further research with larger sample size and longer-term follow-up is warranted.},
}

@article {pmid41230640,
year = {2025},
author = {Sargeant, S and Wilkinson, S and Lorraway, M and McDonald, S},
title = {Contested illness and communication: Positioning long Covid in online discussion forums.},
journal = {Journal of health psychology},
volume = {},
number = {},
pages = {13591053251389517},
doi = {10.1177/13591053251389517},
pmid = {41230640},
issn = {1461-7277},
abstract = {The World Health Organization (WHO) officially acknowledged long COVID as a post COVID-19 condition in 2021. Emerging research shows that long COVID may be considered a contested illness due to unknown causal mechanisms, diagnostic uncertainty, poor recovery/treatment outcomes and people reporting illness dismissal experiences when seeking healthcare. Informed by the sick role and positioning theories, this study explored people's experiences of seeking healthcare for long COVID by examining posts in two online forums (Mayo Clinic Connect and Reddit, from June and July 2023). Template analysis helped to identify12 forum threads containing a total of 305 posts. Inductive thematic analysis of posts identified three themes: (a) 'The concept of time', (b) 'The importance of symptom legitimacy', and (c) 'Responding to diagnostic dismissal'. Healthcare professionals are critical in validating the patient experience without a formal long COVID diagnosis, and in supporting long COVID recovery needs by acknowledging heterogeneity and diagnostic difficulties.},
}

@article {pmid41228073,
year = {2025},
author = {Cianciulli, A and Santoro, E and Manente, R and Pacifico, A and Barberio, I and Satriani, V and Boccia, G},
title = {Clinical and Symptom Profiles of Long-COVID Patients in Italy: A Cross-Sectional Analysis.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {21},
pages = {},
pmid = {41228073},
issn = {2227-9032},
abstract = {Background/Objectives: Long COVID is a multisystemic condition persisting beyond the acute phase of SARS-CoV-2 infection. Data on young, community-dwelling adults in Italy remain limited. To describe the sociodemographic, clinical, and symptom profiles of Long-COVID patients in an Italian cohort. Methods: Cross-sectional survey (February-April 2025) on 250 adults with prior COVID-19. A validated 24-item questionnaire was administered. Descriptive statistics, 95% confidence intervals (CIs), Hedges' g effect sizes, and exploratory subgroup analyses (sex, age ≤ 30 vs. >30) were performed. Results: Participants were 63.6% female, 56% ≤ 30 years, 4.4% with comorbidities. Acute symptoms included muscle/joint pain (2.79 ± 1.31), weakness (2.77 ± 1.28), and tiredness (2.76 ± 1.31). Persistent symptoms were excessive tiredness (2.36 ± 1.27), weakness (2.25 ± 1.29), and muscle/joint pain (2.25 ± 1.25). Acute → persistent changes were significant (p < 0.01, paired t-test) with effect sizes g = 0.31-0.42. Women reported higher persistent fatigue (mean diff = 0.40, 95% CI 0.01-0.78, p = 0.04). Conclusions: Even among young adults without comorbidities, Long COVID imposes a relevant burden. Findings highlight the need for multidisciplinary pathways, nursing-led follow-up, and targeted self-management education.},
}

@article {pmid41228071,
year = {2025},
author = {Neba, R and Pedaprolu, LS and Neba, B and Sambamoorthi, U},
title = {Long COVID Is Associated with Excess Direct Healthcare Expenditures Among Adults in the United States.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {21},
pages = {},
pmid = {41228071},
issn = {2227-9032},
abstract = {Background: Long COVID can lead to a considerable economic burden because of ongoing care for persistent symptoms such as fatigue, dyspnea, or cognitive dysfunction. However, systematic research quantifying healthcare expenditures associated with long COVID remains limited. Objective: This study estimated the excess total, payer, and out-of-pocket healthcare expenditures associated with long COVID among adults in the United States (US). Methods: This was a cross-sectional analysis on adults ≥18 years using 2022 Medical Expenditure Panel Survey (MEPS) data (N = 17,119; representing approximately 254 million adults). Economic burden was measured with (1) total, (2) payer, and (3) out-of-pocket expenditures by individuals and their families. Generalized linear models (GLMs) with gamma distribution and log link were utilized to estimate excess expenditures associated with long COVID after adjusting for age, sex, race and ethnicity, social determinants of health, health status, and lifestyle factors. Results: Overall, 7.0% of the population reported long COVID. Adults with long COVID exhibited higher total (USD 11,305 vs. USD 7162) and payer (USD 9983 vs. USD 6097) expenditures compared to those with no COVID. In a fully adjusted analysis, long COVID was associated with an excess of USD 4098 in total healthcare expenditures and USD 3705 in payer expenditures. We did not observe significant differences in out-of-pocket expenditures between those with long COVID and no COVID. Conclusions: Adults with long COVID had 1.5 times higher total healthcare costs compared to those without COVID. This study highlights the need for comprehensive strategies and policies to reduce the economic burden associated with long COVID.},
}