@article {pmid41051570,
year = {2025},
author = {Zadeh, S and Robbins, N and Hernandez, R and Bryarly, M and Vernino, S},
title = {Letter to the editor 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 = {41051570},
issn = {1619-1560},
}

@article {pmid41050528,
year = {2025},
author = {Kranck, G and Ståhlberg, M and Andersson, U and Lundin, J and Fedorowski, A},
title = {Monitoring of cardiorespiratory vagal desynchrony using novel biomarkers derived from smartwatch electrocardiograms in a patient recovering from long COVID: case report.},
journal = {European heart journal. Case reports},
volume = {9},
number = {10},
pages = {ytaf425},
pmid = {41050528},
issn = {2514-2119},
abstract = {BACKGROUND: Long COVID and cardiovascular autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), present significant healthcare challenges. Long-term monitoring is challenging due to the evolving nature of symptoms and the limited availability of objective diagnostic tools. With over 200 million electrocardiogram (ECG)-enabled smartwatches sold worldwide, these devices offer a promising solution for at-home diagnostics and disease tracking.

METHODS AND RESULTS: This study examines a 35-year-old male with long COVID, POTS, and chronic fatigue syndrome (CFS), who recorded 328 ECGs over using a Samsung smartwatch. The protocol required ECG recordings to be taken first in a sitting posture, followed by a standing position, with slow, controlled breathing. For testing, the patient used a Samsung smartwatch to perform a 30-s hand-to-hand single-lead ECG while engaging in 0.1 Hz diaphragmatic controlled breathing, consisting of 5 s of inhalation followed by 5 s of exhalation (Appendix 1). S-/R-peak amplitude ratios, heart rhythm changes, and other biomarkers were analysed to assess autonomic function. Fatigue levels were self-reported via the BREATHE FLOW app using a three-grade scale, and health status was tracked monthly with the EQ-5D-5L model. Initially, the patient experienced severe fatigue and heart rhythm changes consistent with POTS. Electrocardiogram analysis revealed an increased S-wave amplitude and higher S/R ratio in standing posture, along with worsening respiratory sinus arrhythmia (RSA), indicating cardiorespiratory desynchrony. Over time, as symptoms improved, heart rate responses between sitting and standing normalized, and S/R ratio and RSA index followed self-reported fatigue levels, including fluctuations due to post-exercise fatigue.

CONCLUSION: Smartwatch-derived S-/R-wave amplitude ratio may serve as an accessible biomarker for tracking disease progression in long COVID. Given the widespread availability of smartwatches, standardized at-home protocols could improve diagnostics and monitoring for autonomic dysfunction.},
}

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

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

@article {pmid41048268,
year = {2025},
author = {Dale, Z and Wallington, SF and Penn-Marshall, M},
title = {Prevalence and characteristics of post-acute sequelae of COVID-19 in recovered patients.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1648961},
pmid = {41048268},
issn = {2296-2565},
mesh = {Humans ; *COVID-19/epidemiology/complications ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Risk Factors ; Adult ; Texas/epidemiology ; Post-Acute COVID-19 Syndrome ; Prevalence ; SARS-CoV-2 ; Aged ; Severity of Illness Index ; Comorbidity ; },
abstract = {INTRODUCTION: Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection, has emerged as a major public health concern following the COVID-19 pandemic. Although initially perceived as a respiratory illness, growing biomedical evidence confirms that COVID-19 affects multiple organ systems. This study aimed to explore the clinical manifestations, risk factors, and long-term outcomes associated with long COVID and to identify patients at highest risk. The research also contributes to the ongoing discourse on establishing a unified definition of long COVID.

METHODS: A secondary analysis of a cross-sectional, community-based study was conducted using data from 168 households, representing a weighted total of 14,769 households in Third Ward, Houston, Texas. Data were collected via interviewer-administered surveys and included variables on demographics, pre-existing comorbidities, COVID-19 symptom severity, and post-acute symptom persistence. Symptom variables were recoded as binary indicators, and weighted logistic regression models were applied to identify associations between acute phase characteristics and the development of long COVID.

RESULTS: Risk factors significantly associated with long COVID included symptom severity during acute infection (OR = 29.58, 95% CI [1.38, 632.53]), heart disease (OR = 6.00, 95% CI [1.15, 31.28]), asthma (OR = 3.49, 95% CI [1.05, 11.59]), and poor physical health (OR = 4.20, 95% CI [1.12, 15.75]). Acute symptoms predictive of long COVID included anxiety (OR = 22.94, 95% CI [2.01, 262.31]), chest pain (OR = 7.15, 95% CI [1.13, 45.23]), constipation (OR = 16.81, 95% CI [1.33, 213.23]), heart palpitations (OR = 6.59, 95% CI [1.08, 40.18]), and shortness of breath (OR = 4.97, 95% CI [1.16, 21.36]). No statistically significant associations were found between long COVID and race, education, or income.

CONCLUSION: The findings underscore the multisystemic nature of long COVID, characterized by a diverse range of symptoms including fatigue, cognitive impairment, shortness of breath, and neuropsychiatric issues such as depression. While clinical factors are critical in understanding long COVID, the results also suggest that addressing associated health outcomes requires broader consideration of social determinants of health.},
}

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

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

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

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

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

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

@article {pmid41046766,
year = {2025},
author = {Reséndiz-Vazquez, J and Domínguez-Reyes, V and Terán-Paredes, E and Madero-Franco, N and Chávez-González, A and Majluf-Cruz, A and Alvarado-Moreno, JA},
title = {Deep Venous Thrombosis in Patients Recovered from COVID-19: A Long-Term Sequel.},
journal = {Archives of medical research},
volume = {57},
number = {3},
pages = {103305},
doi = {10.1016/j.arcmed.2025.103305},
pmid = {41046766},
issn = {1873-5487},
abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19 disease has the ability to generate sequelae that extend for weeks or months, giving rise to long-term COVID-19 disease. This condition reduces patients' quality of life and predisposes them to several alterations, including failures in the blood coagulation system. Our laboratory has previously demonstrated abnormalities in endothelial colony-forming cells (ECFCs) of patients recovered from COVID-19.

OBJECTIVE: To analyze the functional state of ECFCs in patients who experienced venous thromboembolic disease (VTD) or arterial thrombosis (AT) during long COVID-19, or post-COVID condition (PCC).

METHODS: We compared 35 samples of peripheral blood (PB) mononuclear cells (MNCs) from patients with a thrombotic event (who had a healthy lifestyle before infection and were vaccinated) with 10 healthy volunteers and 10 samples from patients with a history of recurrent unprovoked VTD (rVTD) after a COVID-19 infection. The samples were cryopreserved in our laboratory and matched by age 25-50 years old and sex. The frequency, morphological characteristics, proliferation and angiogenic ability of ECFCs were evaluated in all samples.

RESULTS: There were no significant differences between male and female patients, and the laboratory data did not indicate risk factors for VTD or AT. The frequency of ECFCs was not different between controls and patients, but a reduced proliferative capacity, a high percentage of senescence and non-angiogenic activity were observed in VTD samples.

CONCLUSIONS: Our results demonstrate a strong association between VTD events in patients with PCC who had a healthy lifestyle prior to infection and ECFCs dysfunction.},
}

@article {pmid41044760,
year = {2025},
author = {Lillieberg, E and Ertzgaard, P and Fernlund, E and Duchen, K and Rytterström, P and Angelhoff, C},
title = {Experiences of living with long COVID during childhood and adolescence: a qualitative study from the child's perspective.},
journal = {BMC pediatrics},
volume = {25},
number = {1},
pages = {754},
pmid = {41044760},
issn = {1471-2431},
mesh = {Humans ; Child ; Adolescent ; Qualitative Research ; *COVID-19/psychology ; Male ; Female ; Adaptation, Psychological ; Interviews as Topic ; Chronic Disease ; Fatigue/psychology ; SARS-CoV-2 ; },
abstract = {BACKGROUND: In February 2023, the World Health Organization (WHO) defined long COVID in children, highlighting limited knowledge about its psychosocial impact. Studies show it as a complex, long-lasting condition affecting multiple systems. WHO and researchers emphasise the need for more understanding, particularly its effect on daily life. The aim of this study was to explore how life is experienced and how it changed whilst living with long COVID during childhood.

METHODS: We present a qualitative study with an inductive and exploratory approach. Between October 2022 and March 2024, 16 children between 9 and 18 years old diagnosed with long COVID were interviewed face-to-face using a semi-structured interview guide. The results were analysed using reflexive thematic analysis by Braun and Clarke.

RESULTS: The results present the subjective reality of children suffering from long COVID and their struggle in daily life. The findings are presented through three themes: Losing my foothold, Fatigue decides my path, and My way forward, illustrating a temporal and emotional journey, reflecting how children make sense of their experiences, adapt to the persistent impact of long COVID, and gradually move toward acceptance.

CONCLUSIONS: This study addresses the lack of knowledge of long COVID in the society, how it affects children in their struggle to find a new path in life. It also shows that, with knowledge and support, the symptoms and the burden of the condition can decrease or even pass. It is important that people around these children, including health care, school and family, use this knowledge to promote health and avoid educational, health and social problems at a vulnerable time in life.},
}

Humans
Child
Adolescent
Qualitative Research
*COVID-19/psychology
Male
Female
Adaptation, Psychological
Interviews as Topic
Chronic Disease
Fatigue/psychology
SARS-CoV-2

@article {pmid41044528,
year = {2025},
author = {Portela, MC and Lima, SML and Escosteguy, CC and Martins, M and de Vasconcellos, MTL and Caldas, BDN and Bernardino, M and Baginski, NP and Góes, G and Sabaine, B and Furtado, D and Cavalcanti, M and Soares, L and Stelson, E and Singer, S and Cornish, F and Aveling, EL},
title = {Long COVID in the population of COVID-19 hospitalized patients discharged from SUS' hospitals in Rio de Janeiro City, Brazil: a patient-engaged cohort survey study.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1232},
pmid = {41044528},
issn = {1471-2334},
abstract = {BACKGROUND: Long COVID (LC) is a global health concern, affecting millions and placing significant strain on healthcare systems. However, there is a notable lack of LC research in low- and middle-income countries, particularly in the global south. This study aims to fill this gap by focusing on Brazil, a country with an emerging LC literature but limited population estimates due to sampling constraints. Our unique focus is to estimate the prevalence of persistent symptoms and LC self-reported diagnosis among COVID-19 patients hospitalized in Rio de Janeiro City public hospitals. We also aim to identify factors associated with the LC measures and most frequent symptoms, providing valuable insights for healthcare systems and policymakers.

METHODS: We designed a comprehensive, patient-engaged cohort survey study to assess LC symptoms and administered it to a probability sample of adults six to 24 months post-discharge from public hospitals in Rio de Janeiro City. LC was measured as (i) at least one persistent symptom or (ii) self-reported LC. Among the symptoms, we considered post-exertional malaise, which is frequently neglected in LC studies. Additionally, we applied an adaptation of the DePaul Symptom Questionnaire to account not only for the presence but also the frequency of symptom occurrence. We estimate the prevalence of symptoms and use logistic regression models to identify associations between LC and the most frequent LC symptoms and independent variables, assessing demographic, socioeconomic, lifestyle, and clinical characteristics, vaccination, and severity of acute disease.

RESULTS: Results indicate the predominant study's focus on low-income and highly vulnerable people, with an elevated prevalence of comorbidities before LC. In the study population of 11,328 persons, 71.3% (95%CI 66.3; 76.2) reported frequently experiencing at least one persistent symptom, and 39.3% (95%CI 34.2; 44.4) self-reported having LC. The most frequent symptoms were fatigue, post-exertional malaise, joint pain, sleep disturbance, and cognitive impairment, and symptoms were consistently more likely to occur among women. Age was non-linearly related to LC, and comorbidities before COVID-19 hospitalization were positively associated with LC symptoms.

CONCLUSIONS: Evidence is provided for the LC burden among COVID-19 hospitalized patients even 24 months post-discharge. LC accessible and appropriate healthcare is fundamental.},
}

@article {pmid41043444,
year = {2025},
author = {Buonsenso, D},
title = {Long COVID is here to stay-even in children.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00496-7},
pmid = {41043444},
issn = {1474-4457},
}

@article {pmid41043442,
year = {2025},
author = {Zhang, B and Wu, Q and Jhaveri, R and Zhou, T and Becich, MJ and Bisyuk, Y and Blanceró, F and Chrischilles, EA and Chuang, CH and Cowell, LG and Fort, D and Horowitz, CR and Kim, S and Ladino, N and Liebovitz, DM and Liu, M and Mosa, ASM and Schwenk, HT and Suresh, S and Taylor, BW and Williams, DA and Morris, JS and Forrest, CB and Chen, Y and , },
title = {Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective cohort study.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(25)00476-1},
pmid = {41043442},
issn = {1474-4457},
abstract = {BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) remain a major public health challenge. Although previous studies have focused on characterising PASC in children and adolescents after an initial infection, the risks of PASC after reinfection with the omicron variant remain unclear. We aimed to assess the risk of PASC diagnosis (U09.9) and symptoms and conditions potentially related to PASC in children and adolescents after a SARS-CoV-2 reinfection during the omicron period.

METHODS: This retrospective cohort study used data from 40 children's hospitals and health institutions in the USA participating in the Researching COVID to Enhance Recovery (RECOVER) Initiative. We included patients younger than 21 years at the time of cohort entry; with documented SARS-CoV-2 infection after Jan 1, 2022; and who had at least one health-care visit within 24 months to 7 days before the first infection. The second SARS-CoV-2 infection was confirmed by positive PCR, antigen tests, or a diagnosis of COVID-19 that occurred at least 60 days after the first infection. The primary endpoint was a clinician-documented diagnosis of PASC (U09.9). Secondary endpoints were 24 symptoms and conditions previously identified as being potentially related to PASC. We used the modified Poisson regression model to estimate the relative risk (RR) between the second and first infection episodes, adjusted for demographic, clinical, and health-care utilisation factors using exact and propensity-score matching.

FINDINGS: We identified 407 300 (87·5%) of 465 717 eligible children and adolescents with a first infection episode and 58 417 (12·5%) with a second infection episode from Jan 1, 2022, to Oct 13, 2023, in the RECOVER database. 233 842 (50·2%) patients were male and 231 875 (49·8%) were female. The mean age was 8·17 years (SD 6·58). The incident rate of PASC diagnosis (U09.9) per million people per 6 months was 903·7 (95% CI 780·9-1026·5) in the first infection group and 1883·7 (1565·1-2202·3) in the second infection group. Reinfection was associated with a significantly increased risk of an overall PASC diagnosis (U09.9) (RR 2·08 [1·68-2·59]) and a range of symptoms and conditions potentially related to PASC (RR range 1·15-3·60), including myocarditis, changes in taste and smell, thrombophlebitis and thromboembolism, heart disease, acute kidney injury, fluid and electrolyte disturbance, generalised pain, arrhythmias, abnormal liver enzymes, chest pain, fatigue and malaise, headache, musculoskeletal pain, abdominal pain, mental ill health, POTS or dysautonomia, cognitive impairment, skin conditions, fever and chills, respiratory signs and symptoms, and cardiovascular signs and symptoms.

INTERPRETATION: Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings add to previous evidence linking paediatric long COVID to multisystem effects and highlight the need to promote vaccination in younger populations and support ongoing research to better understand PASC, identify high-risk subgroups, and improve prevention and care strategies.

FUNDING: National Institutes of Health.},
}

@article {pmid41043208,
year = {2025},
author = {Li, M and Wisniewski, T and Silva, F and Hammam, S and Alvarez, Z and Bilici, N and Caceres, LC and De La Cruz, N and Engelson, C and Greenberg, J and Gummadi, B and Hunter, J and Hernandez, DI and Karimi, S and Links, J and Rodriguez, M and Vedvyas, A and Vinitsky, H and Yakubov, A and Ge, Y and Thawani, S and Balcer, L and Galetta, S and Frontera, JA},
title = {Functional and cognitive outcomes three years after COVID-19.},
journal = {Clinical neurology and neurosurgery},
volume = {258},
number = {},
pages = {109180},
doi = {10.1016/j.clineuro.2025.109180},
pmid = {41043208},
issn = {1872-6968},
abstract = {BACKGROUND: There is paucity of data on long-term functional and cognitive outcomes after COVID-19 compared to COVID-negative controls.

METHODS: We conducted an observational cohort study of patients ≥ 1 year after COVID-19 compared to contemporaneous COVID-19 negative controls (SARS-CoV-2 nucleocapsid IgG negative with no history of COVID-19). Functional (modified Rankin Scale [mRS], Barthel Index), cognitive (telephone MoCA [t-MoCA]), and patient-reported neuropsychiatric symptoms were compared between groups using multivariable logistic regression analysis. In a subgroup of COVID-19 patients who were followed longitudinally, trajectories of recovery were assessed using the paired samples Sign test.

RESULTS: Of 145 participants, N = 115 COVID-19 patients (median age 62, 51 % female, 33 % hospitalized for COVID-19, median 2.9 years from index infection), and N = 30 non-COVID-19 controls (median age 75, 70 % female) were enrolled. Neuropsychiatric symptoms were reported in 76 % of COVID-19 patients versus 7 % of controls (aOR 15.0, 95 %CI 3.09-72.47, P < 0.001). Abnormal mRS> 0 occurred in 42 % of COVID-19 patients compared to 11 % of controls (P = 0.002). However, this difference was not significant after adjusting for age, sex, COVID-19 hospitalization and history of mood disorder (aOR 2.10, 95 %CI 0.52-8.51). Rates of abnormal t-MoCA≤ 18 (40 % of COVID-19 versus 41 % of controls, P = 1.00) and Barthel scores< 100 (19 % of COVID-19 versus 14 % in controls, P = 0.785) were similar. Among N = 26 COVID-19 patients with repeated measures, mRS significantly improved between 6-months to 3-years post-COVID (+1.3 points, p = 0.004), while no changes were observed in t-MoCA or Barthel.

CONCLUSIONS: Three years after COVID-19, neuropsychiatric symptoms were significantly more frequent compared to controls, however no differences in functional or cognitive status were detected.},
}

@article {pmid41042487,
year = {2025},
author = {Joost, FEA and Rose, N and Kimmig, A and Ruhnke, T and Dröge, P and Freytag, A and Günster, C and Pletz, MW and Roesler, M and Reuken, PA and Schlattmann, P and Schmidt, KFR and Stallmach, A and Storch, J and Reinhart, K and Wedekind, L and Fleischmann-Struzek, C},
title = {Long-term outcomes after intensive care unit-treated COVID-19, influenza and respiratory sepsis in 2020 - a comparative, population-based cohort study.},
journal = {Infection},
volume = {},
number = {},
pages = {},
pmid = {41042487},
issn = {1439-0973},
support = {01VSF21031//German Innovations Fund of the Federal Joint Committee/ ; },
abstract = {BACKGROUND: Sepsis survivors are affected by a broad spectrum of long-term impairments, which overlap with Long-Covid and sequelae after influenza in their clinical presentation. However, we lack comparative assessments on the burden of long-term outcomes, particularly with patients being recruited from the same, contemporary patient population. Therefore we compared long-term outcomes after respiratory sepsis (RS), SARS-CoV-2-associated sepsis (SS) and influenza-associated sepsis (IS).

METHODS: Retrospective, population-based cohort study. We included patients > 15 years hospitalized with RS, SS and IS between 01/2020 and 12/2020 in Germany, who received intensive care unit treatment. We compared mortality, readmissions, prevalence of diagnoses in the cognitive, psychological or medical domain, and the number of impaired domains in the 12 months post-discharge between the three survivor cohorts, adjusting for between-group differences in relevant covariates by inverse propensity score weighting based on generalized propensity scores.

RESULTS: Our study included 12,854 patients, of which 8,201 were RS, 3,964 SS and 689 IS survivors. RS survivors had a considerably higher risk for 12-month mortality compared to SS and IS survivors (relative risk, 1.77 [95% CI, 1.54-2.03]; P < 0.001 and relative risk, 1.37 [95% CI, 1.14-1.65]; P = 0.001, respectively). They were more often rehospitalized, affected by multiple domain impairments, cognitive decline and impairments related to the severity of acute disease, e.g. complications of the tracheostoma, compared to survivors after SS and IS. RS survivors had a lower risk for being affected by medical diagnoses compared to SS. Risks for psychological diagnoses did not differ between RS and the other survivor groups.

CONCLUSIONS: Although respiratory sepsis survivors seem to be affected by more severe long-term impairments, the overall burden of post-acute sequelae among all survivor groups is high. This warrants efforts to provide targeted aftercare for all survivor populations after life-threatening infections.},
}

@article {pmid41041184,
year = {2025},
author = {Anjum, A and Rauf, I and Mehvish, S and Parveen, S and Hussain, A},
title = {A cross-sectional study on long covid, cognition and neurasthenia-one year post covid.},
journal = {Journal of family medicine and primary care},
volume = {14},
number = {8},
pages = {3205-3210},
pmid = {41041184},
issn = {2249-4863},
abstract = {INTRODUCTION: The COVID-19 pandemic has led to long-term health effects in some patients, known as long COVID. This study aimed to delineate the symptoms of long COVID-19 and determine the presence of neurasthenia in patients one year after COVID-19 infection while excluding other potential causes of fatigue.

METHODS: A cross-sectional study was conducted on 512 RT-PCR-confirmed COVID-19 patients attending a follow-up clinic at least one year after infection. After excluding patients above 60 years, those with pre-existing psychiatric disorders, medical co-morbidities, and current psychiatric diagnoses, 87 patients were included in the final analysis. Patients were evaluated using the Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Fatigue Severity Scale (FSS), and memory scale of PGI-BBD. A semi-structured questionnaire assessed changes in activities of daily living.

RESULTS: Of the 87 patients, 43 (49.4%) fulfilled the ICD-10 criteria for neurasthenia. Fatigue interfering with daily activities was reported by 41.3% of patients, with a mean FSS score of 6.1 in those with neurasthenia. Other symptoms included muscular aches (35.6%), tension headaches (27.5%), and weakness (31%). Cognitive difficulties, specifically problems with attention and concentration, were observed in 8% of patients. The severity of the initial COVID-19 infection did not correlate with the risk of developing neurasthenia.

CONCLUSION: Long COVID symptoms, particularly those resembling neurasthenia, persist in a significant proportion of patients one year after infection. The syndrome of long COVID shows similarities to the ICD-10 diagnosis of neurasthenia, suggesting a potential link between post-COVID symptoms and chronic low-grade inflammation. These findings highlight the need for recognition and management of long-term COVID-19 effects in public health policies.},
}

@article {pmid41038893,
year = {2025},
author = {da Silva Almeida, I and de Jesus Ferreira, LG and Cipriano, G and Costa, RR and Vaz, MA and Babault, N and de Cássia Marqueti, R and Durigan, JLQ},
title = {Persistent neuromuscular disorders associated with changes in tibialis anterior and gastrocnemius lateralis muscle architecture in long-covid: an observational longitudinal study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34375},
pmid = {41038893},
issn = {2045-2322},
support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 00193.00000773/2021-72//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 00193.00001222/2021-26//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 00193-00001261/2021-23//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 141130/2023-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 131422/2023-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309435/2020-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 310269/2021-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 00193.00000859/2021-3//Fundação de Apoio à Pesquisa do Distrito Federal, Brazil/ ; },
mesh = {Humans ; Male ; *Muscle, Skeletal/diagnostic imaging/pathology/physiopathology ; Female ; *COVID-19/complications/physiopathology ; Longitudinal Studies ; Middle Aged ; Adult ; *Neuromuscular Diseases/etiology/physiopathology/pathology/diagnostic imaging ; SARS-CoV-2 ; Ultrasonography ; },
abstract = {Long COVID-19 causes complications, affecting quality of life and work capacity. However, its long-term impact on lower limb neuromuscular function remains unclear. To evaluate neuromuscular electrophysiological disorders (NEDs) and muscle architecture of the tibialis anterior (TA) and triceps surae (TS) in individuals with moderate or severe COVID-19 compared to control group over 12 months. Seventy participants were divided into moderate-COVID (n = 22), severe-COVID (n = 18), and control (n = 30) groups. COVID groups underwent four assessments over one year. NEDs in the TA and gastrocnemius lateralis (GL) were assessed via stimulus electrodiagnostic testing, while TA and TS muscle architecture was evaluated using ultrasound. Participants with severe-COVID exhibited significantly higher chronaxie (p < 0.001) in the TA at the first assessment, NEDs were observed in 55.55%, 33.33%, and 16.66% of participants across the first three assessments. GL showed 5.55% prevalence of NEDs. Echogenicity increased in TA and GL muscles in the severe-COVID group (p < 0.001). An association was found between TA chronaxie and echogenicity in the COVID groups during the short-term assessment (p < 0.001). Severe COVID-19 is associated with higher prevalence of NEDs in the TA muscle and persistent echogenicity increases, suggesting polyneuromyopathy in the TA and widespread echogenicity abnormalities in long COVID patients.},
}

Humans
Male
*Muscle, Skeletal/diagnostic imaging/pathology/physiopathology
Female
*COVID-19/complications/physiopathology
Longitudinal Studies
Middle Aged
Adult
*Neuromuscular Diseases/etiology/physiopathology/pathology/diagnostic imaging
SARS-CoV-2
Ultrasonography

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

@article {pmid41037811,
year = {2025},
author = {Metz, TD and Reeder, HT and Clifton, RG and Flaherman, V and Aragon, LV and Baucom, LC and Beamon, CJ and Braverman, A and Brown, J and Carmilani, M and Cao, T and Chang, A and Costantine, MM and Dionne, JA and Gibson, KS and Gross, RS and Guerreros, E and Habli, M and Hess, R and Hillier, L and Hodder, S and Hoffman, MC and Hoffman, MK and Huang, W and Hughes, BL and Jia, X and Kale, M and Katz, SD and Laleau, V and Mendez-Figueroa, H and McComsey, GA and Ofotokun, I and Okumura, MJ and Pacheco, LD and Palatnik, A and Palomares, KTS and Parry, S and Pettker, CM and Plunkett, BA and Poppas, A and Ramsey, P and Reddy, UM and Rouse, DJ and Saade, GR and Sandoval, GJ and Sciurba, F and Simhan, HN and Skupski, DW and Sowles, A and Thorp, JM and Tita, ATN and Wiegand, S and Weiner, SJ and Yee, LM and Horwitz, LI and Foulkes, AS and Jacoby, VL and , },
title = {Long COVID After Acquisition of the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) During Pregnancy Compared With Outside of Pregnancy.},
journal = {Obstetrics and gynecology},
volume = {},
number = {},
pages = {},
pmid = {41037811},
issn = {1873-233X},
support = {OT2HL161847/HL/NHLBI NIH HHS/United States ; OT2HL161841/HL/NHLBI NIH HHS/United States ; },
abstract = {OBJECTIVE: To evaluate whether the risk of long COVID among individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy differs from that of individuals who were not pregnant at time of virus acquisition.

METHODS: We conducted a multicenter observational cohort study at 79 NIH RECOVER (Researching COVID to Enhance Recovery) sites. Individuals assigned female at birth aged 18-45 years with an index (first) SARS-CoV-2 infection on or after December 1, 2021, were included. The exposure was pregnancy (any gestational age) at the time of index SARS-CoV-2 infection. The primary outcome was long COVID 6 months after index infection, defined as RECOVER-Adult Long COVID Research Index score 11 or higher based on a detailed symptom survey. To account for confounding and differential selection between participants who were pregnant and not pregnant at infection, propensity score-matching methods were used to balance the groups on variables potentially associated with both pregnancy status and long COVID.

RESULTS: Overall 2,423 participants were included; 580 (23.9%) were pregnant at index SARS-CoV-2 infection. The median age at infection was 33 years (interquartile range 28-38 years), and 2,131 of participants (90.0%) with known vaccination status were vaccinated. After propensity score matching, the adjusted long COVID prevalence estimates 6 months after index infection were 10.2% (95% CI, 6.2-14.3%) among those pregnant at infection and 10.6% (95% CI, 8.8-12.4%) among those not pregnant at infection. Pregnancy was not associated with a difference in adjusted risk of long COVID (adjusted risk ratio 0.96, 95% CI, 0.63-1.48).

CONCLUSION: Acquisition of SARS-CoV-2 during pregnancy was not associated with a differential risk of long COVID at 6 months compared with similar-aged individuals who acquired SARS-CoV-2 outside of pregnancy.},
}

@article {pmid41036702,
year = {2025},
author = {Thierry, AR and Usher, T and Sanchez, C and Turner, S and Venter, C and Pastor, B and Waters, M and Thompson, A and Mirandola, A and Pisareva, E and Prevostel, C and Laubscher, GJ and Kell, DB and Pretorius, E},
title = {Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients.},
journal = {Journal of medical virology},
volume = {97},
number = {10},
pages = {e70613},
doi = {10.1002/jmv.70613},
pmid = {41036702},
issn = {1096-9071},
support = {//The study was partially supported by SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553 (ART); South African National Research Foundation (142142); (EP); and the South African Medical Research Foundation (EP), the Novo Nordisk Foundation grant NNF20CC0035580 (DBK) and the Balvi Foundation grant 18 (DBK)./ ; },
mesh = {Humans ; *Extracellular Traps/metabolism ; *COVID-19/blood/complications/pathology ; Male ; Middle Aged ; Female ; Leukocyte Elastase/blood ; *Neutrophils/metabolism ; Biomarkers/blood ; Aged ; Fibrin/metabolism ; SARS-CoV-2 ; Adult ; },
abstract = {The persistence of vasculo-thrombotic complications has been put forward as a possible contributing factor in the Long COVID (LC) syndrome. Given the recently reported separate demonstration of the association of LC with elevated levels of heterogenous fibrin(ogen) amyloidogenic particles (microclots) and with those neutrophil extracellular traps (NETs), markers that are linked to thromboinflammation, this study considers the association of microclots with NETs. The results show that NETs markers (Myeloperoxydase, Neutrophil Elastase, and circulating DNA) are quantitatively and structurally associated with the size and number of microclots in patients with LC. These markers showed a strong diagnostic performance, both independently and when combined. Our study revealed that NETs may be a component of circulating microclots. We suggest that higher NETs formation might promote the stabilization of microclots in the circulation, potentially leading to deleterious effects which contribute causally to the LC syndrome.},
}

Humans
*Extracellular Traps/metabolism
*COVID-19/blood/complications/pathology
Male
Middle Aged
Female
Leukocyte Elastase/blood
*Neutrophils/metabolism
Biomarkers/blood
Aged
Fibrin/metabolism
SARS-CoV-2
Adult

@article {pmid41036177,
year = {2025},
author = {Fujimoto, Y and Abe, H and Eiro, T and Tsugawa, S and Tanaka, M and Hatano, M and Nakajima, W and Ichijo, S and Arisawa, T and Takada, Y and Kimura, K and Sano, A and Hirahata, K and Sasaki, N and Kimura, Y and Takahashi, T},
title = {Systemic increase of AMPA receptors associated with cognitive impairment of long COVID.},
journal = {Brain communications},
volume = {7},
number = {5},
pages = {fcaf337},
pmid = {41036177},
issn = {2632-1297},
abstract = {Long COVID primarily presents with persistent cognitive impairment (Cog-LC), imposing a substantial and lasting global burden. Even after the pandemic, there remains a critical global need for diagnostic and therapeutic strategies targeting Cog-LC. Nevertheless, the underlying neural mechanisms remain poorly understood. Given the central role of synapses in brain function, investigation of synaptic molecular changes may provide vital insights into Cog-LC pathophysiology. In this study, we used [[11]C]K-2 PET to characterize the density of AMPA receptors (AMPARs) on the post-synaptic cell surface, which are crucial synaptic components in brain signalling. Statistical parametrical mapping was used to spatially normalize and apply independent t-test for a voxel-based comparison. We selected patients with Cog-LC (n = 30) based on Repeatable Battery for the Assessment of Neuropsychological Status assessed persistent cognitive impairment and healthy controls (n = 80) with no diagnosed neuropsychiatric disorders. The primary objective was to compare [[11]C]K-2 standardized uptake value ratio with white matter (SUVRWM) as a reference region between patients with Cog-LC and healthy controls, and to define the regional extent of differences. The secondary objective was to examine associations between [[11]C]K-2 SUVRWM and plasma concentrations of cytokines or chemokines. As an exploratory objective, we tested whether [[11]C]K-2 PET data could distinguish Cog-LC from healthy controls using a partial least squares based classification algorithm. A voxel-based comparison (P < 0.05, T > 1.66, one-tailed, false discovery rate control) and a volume of interests analysis (P < 0.05, Bonferroni multiple comparison) demonstrated that increased index of AMPAR density in large parts of the brains of patients with Cog-LC compared with that in healthy controls. A voxel-based correlation analysis also showed the brain regions where [[11]C]K-2 SUVRWM correlated positively with plasma TNFSF12 and negatively with plasma CCL2 concentrations. A partial least squares model trained on the index of AMPAR density data demonstrated high diagnostic accuracy, achieving 100% sensitivity and 91.2% specificity. [[11]C]K-2 PET signal represents the index of AMPAR density on the post-synaptic neural cell surface, not on the glial cell surface. A systemic increase in synaptic AMPARs across the brain may drive abnormal information processing in Cog-LC and, through excessive excitatory signalling, pose a risk of excitotoxic neuronal damage. We derived the hypothesis that [[11]C]K-2 PET would be helpful in establishing a diagnostic framework for Cog-LC and that antagonists for cell surface AMPARs, such as perampanel, would be a potential therapeutic target. These hypotheses should be investigated in future large-scale clinical studies.},
}

@article {pmid41035536,
year = {2025},
author = {Daher, J and Koberssy, Z and Durieux, JC and Atieh, O and Baissary, J and Abboud, M and McComsey, GA},
title = {Cognitive Function 1 Year After COVID Infection.},
journal = {Open forum infectious diseases},
volume = {12},
number = {10},
pages = {ofaf583},
pmid = {41035536},
issn = {2328-8957},
abstract = {BACKGROUND: While emerging evidence suggests a potential link between COVID-19 and cognitive impairment, there is a lack of prospective longitudinal research that objectively assesses cognitive outcomes after SARS-CoV-2 infection. This study aims to evaluate changes in cognitive function following COVID-19 in a group of individuals with baseline pre-infectious cognitive assessments.

METHODS: In this cohort study, cognitive function was objectively measured using the computerized Cognivue Clarity® device. All participants who had available Cognivue® testing were followed with a second Cognivue® assessment ∼1 year later. Based on whether they contracted COVID-19 during this period, participants were categorized into 2 groups according to COVID status.

RESULTS: We enrolled 110 participants with a median age of 45 years, 35% females and 46% white; 55 (50%) participants experienced a documented COVID-19 infection during the follow-up period (COVID + group), and the rest remained free of COVID infection (COVID- group). COVID- and COVID + groups were balanced for demographics and duration of follow-up. In the COVID + group, only memory scores changed during follow-up (+3.9; P = .03). The COVID- group showed improvements in the overall Cognivue® score (+2; P = .03), as well as in visuospatial (+1.9; P = .04), executive function (+2.2; P = .02), and naming language (+2.2; P = .01) scores. No statistically significant differences were observed in the overall cognitive score or its subdomains between the 2 groups.

CONCLUSIONS: In a 45-year-old average population, no decrease in cognitive function was observed 1 year after COVID-19 infection.},
}

@article {pmid41034315,
year = {2025},
author = {Roy, S and Malik, A and Singh, A and Ray, S},
title = {Long term health related quality of life among individuals after COVID 19 recovery in a multicentric community based study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34225},
pmid = {41034315},
issn = {2045-2322},
support = {OR/3/11/2021-ECD-II//Department of Health Research, Ministry of Health and Family Welfare, Government of India/ ; },
mesh = {Humans ; *Quality of Life ; *COVID-19/epidemiology/psychology ; Male ; Female ; Middle Aged ; Adult ; Cross-Sectional Studies ; Aged ; SARS-CoV-2/isolation & purification ; India/epidemiology ; Young Adult ; Surveys and Questionnaires ; Health Status ; },
abstract = {The COVID-19 pandemic has had a profound and far-reaching impact on global health, resulting in significant morbidity and mortality across populations. Long term post COVID-19 conditions can include neurological symptoms, chronic fatigue, and mental health disorders, which collectively contribute to a deterioration in health-related quality of life. This study aims assess long-term HRQoL using EuroQol (EQ 5D 5L) among COVID-19 patients in community settings. This study conducted a multicentric, community-based cross-sectional design to assess the long-term HRQoL among patients who have recovered from COVID-19. The study included participants aged above 18 years from two cities Delhi and Bhubaneswar. Descriptive statistics of categorical variables were presented in frequency and percentage, while continuous variables were presented in mean ± SD. The censored regression analysis has been performed by reporting beta coefficients and significance by (p < 0.05). The EQ-5D-5L index scores indicated a mean of 0.89 (95% CI 0.87, 0.91) for Delhi, compared to a lower mean score of 0.66 (95% CI 0.62, 0.71) for Bhubaneswar. Age was negatively correlated with health states, showing a crude coefficient of - 0.003 (95% CI - 0.005, 0.001) with a significant p value of 0.002, although the adjusted coefficient was - 0.002 (95% CI - 0.005, 0.001), indicating a loss of significance when controlling for other factors. The emphasizes the health-related quality of life of the COVID-19 recovered patients and challenges in their daily living. The study descriptively highlighting the quality-of-life and in association with age, educational status, marital status, health insurance availability, and treatment setting.},
}

Humans
*Quality of Life
*COVID-19/epidemiology/psychology
Male
Female
Middle Aged
Adult
Cross-Sectional Studies
Aged
SARS-CoV-2/isolation & purification
India/epidemiology
Young Adult
Surveys and Questionnaires
Health Status

@article {pmid41033506,
year = {2025},
author = {Greene, C},
title = {The broken barrier: neurovascular insights into long COVID.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106126},
doi = {10.1016/j.bbi.2025.106126},
pmid = {41033506},
issn = {1090-2139},
}

@article {pmid41033333,
year = {2025},
author = {Johnson, MJ and Williams, B and Keerie, C and Tuck, S and Hart, S and Bajwah, S and Chaudhuri, N and Pearson, M and Cohen, J and Evans, RA and Currow, DC and Higginson, IJ and Hall, P and Atter, M and Norrie, J and Fallon, MT and , },
title = {Morphine for chronic breathlessness (MABEL) in the UK: a multi-site, parallel-group, dose titration, double-blind, randomised, placebo-controlled trial.},
journal = {The Lancet. Respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2213-2600(25)00205-X},
pmid = {41033333},
issn = {2213-2619},
abstract = {BACKGROUND: The effectiveness of opioids for breathlessness seen in laboratory-based studies has not been replicated in clinical trials. We aimed to assess the effectiveness of oral morphine for breathlessness in long-term conditions.

METHODS: This phase 3, parallel-group, double-blind, placebo-controlled trial across 11 centres randomly assigned consenting adults (1:1, stratified by site and causal disease) with a modified Medical Research Council breathlessness score of 3 or more due to cardiorespiratory conditions to receive 5-10 mg twice daily oral long-acting morphine or placebo (as well as a blinded laxative) for 56 days. The primary outcome was worst breathlessness score in the past 24 h at day 28, measured using a numerical rating scale (NRS; 0=not breathless at all; 10=worst imaginable breathlessness). Secondary outcomes included physical activity levels, worst cough NRS, quality of life, and morphine-related toxicities. Patients who received at least one dose of study drug were eligible for inclusion in efficacy and safety analyses. The trial was registered with ISRCTN (ISRCTN87329095) and the EU Clinical Trials Register (EudraCT 2019-002479-33).

FINDINGS: Between March 18, 2021, and Oct 26, 2023, 143 participants were randomly assigned to receive either morphine (73 participants) or placebo (67 participants) and were included in the analyses; three participants did not receive the allocated treatment. Participants had a mean age of 70·5 (SD 9·4) years, were mostly male (93 [66%]), and were mostly White (132 [94%]). By day 28, 64 (88%) participants in the morphine group versus 66 (99%) in the placebo group had 90% adherence or greater. We found no evidence of difference in worst breathlessness at day 28 (morphine 6·19 [95% CI 5·57 to 6·81] vs placebo 6·10 [5·44 to 6·76]; adjusted mean difference 0·09 [95% CI -0·57 to 0·75], p=0·78) or any secondary measure, except for improved cough seen at day 56 (adjusted mean difference -1·41 [-2·18 to -0·64]). Increased moderate to vigorous physical activity was seen at day 28 (adjusted mean difference 9·51 min/day [0·54-18·48]) but this was not significant after multiple-measures correction. The morphine group had more adverse events (251 vs 162), serious adverse events (15 vs three, of which three in the morphine group and zero in the placebo group were deemed to be related to the study), and study drug withdrawals (13 vs two). There were no treatment-related deaths.

INTERPRETATION: We found no evidence that morphine improves worst breathlessness intensity. Further research is needed to understand whether there is any role for morphine in chronic breathlessness, but our findings do not support its use in this setting.

FUNDING: NIHR Health Technology Assessment programme (HTA Project 17/34/01).},
}

@article {pmid41033183,
year = {2025},
author = {Shimada, T and Tanabe, N and Chubachi, S and Asakura, T and Namkoong, H and Tanaka, H and Azekawa, S and Otake, S and Nakagawara, K and Fukushima, T and Watase, M and Maetani, T and Shiraishi, Y and Terai, H and Sasaki, M and Ueda, S and Kato, Y and Harada, N and Suzuki, S and Yoshida, S and Tateno, H and Yamada, Y and Jinzaki, M and Hirai, T and Okada, Y and Koike, R and Ishii, M and Kimura, A and Imoto, S and Miyano, S and Ogawa, S and Kanai, T and Fukunaga, K},
title = {Extent of pulmonary involvement on admission predicts long-term pulmonary and muscular sequelae of COVID-19: A longitudinal computed tomography study.},
journal = {Respiratory investigation},
volume = {63},
number = {6},
pages = {1215-1220},
doi = {10.1016/j.resinv.2025.09.014},
pmid = {41033183},
issn = {2212-5353},
abstract = {BACKGROUND: Studies on the association between chest computed tomography (CT) findings of extensive pulmonary involvement and long-term pulmonary and extrapulmonary coronavirus disease 2019 (COVID-19) sequelae are lacking. This study aimed to investigate the relationship between the severity of pneumonia on admission and residual pulmonary and extrapulmonary complications at three months post-hospitalization.

METHODS: Using data from the Japan COVID-19 Task Force database, we conducted quantitative analysis of CT scans of 164 patients obtained at admission and three months later. The parameters included pneumonia volume, total lung volume, and area and density of the pectoralis muscle (PM), subcutaneous and epicardial adipose tissue, and vertebral bone density.

RESULTS: Patients with extensive pneumonia on admission had high residual pneumonia volumes, reduced lung volumes, and decreased area and density of PM at three months. No significant differences were observed in the adipose tissue or bone parameters. The severity of pneumonia at admission was independently associated with PM atrophy.

CONCLUSIONS: CT-based quantification of pneumonia extent during the acute phase of COVID-19 may be useful in predicting long-term pulmonary sequelae and muscle wasting. This approach may allow the objective evaluation of Long COVID and facilitate the identification of potential therapeutic targets.},
}

@article {pmid41031103,
year = {2025},
author = {Dalton, AF and Baca, S and Raykin, J and Gregory, CO and Boehmer, T and Koumans, EH and Patel, PR and Patel, P and Saydah, S},
title = {Risk of Post-COVID-19 Conditions Among Adolescents and Adults Who Received Nirmatrelvir-Ritonavir for Acute COVID-19: A Retrospective Cohort Study.},
journal = {Open forum infectious diseases},
volume = {12},
number = {10},
pages = {ofaf567},
pmid = {41031103},
issn = {2328-8957},
abstract = {BACKGROUND: Post-COVID-19 Conditions (PCC) potentially affect millions of people, but it is unclear whether treating acute COVID-19 with nirmatrelvir-ritonavir may reduce the risk of PCC.

METHODS: This is a retrospective cohort study using real-world, closed claims data to assess the relationship between nirmatrelvir-ritonavir and PCC by age group (12-17, 18-49, 50-64, ≥65 years). Eligible patients had a COVID-19 index date (positive laboratory test, ICD-10 diagnosis code, or nirmatrelvir-ritonavir prescription) from 1 April to 31 August 2022, in the outpatient, telehealth, or emergency department setting, and had a higher risk of severe COVID-19 based on age (≥50 years) or underlying risk factors. Treated patients (ie, received a nirmatrelvir-ritonavir prescription within ±5 days of index date) were matched 1:2 on age, sex, month of index date, and HHS region with untreated patients. PCC was defined by the presence of ≥1 of 45 new-onset symptoms or conditions recorded ≥60 days after index date.

RESULTS: Of the treated patients, 291 433 were matched to 582 866 untreated patients. Treatment with nirmatrelvir-ritonavir reduced PCC risk in adults 50-64 years (adjusted hazard ratio [aHR] 0.93, 95% confidence interval [CI] 0.92-0.95) and ≥65 years (aHR 0.88, 95% CI 0.87-0.90). Treatment had minimal effect among high-risk adults 18-49 years (aHR 0.98, 95% CI 0.97-0.99) and no effect among high-risk adolescents 12-17 years (aHR 1.06, 95% CI 0.66-1.13).

CONCLUSIONS: Results using real-world data suggest a protective relationship between nirmatrelvir-ritonavir during acute illness and PCC risk among older adults, but not among adolescents. Consideration may be given to outpatient treatment of mild to moderate COVID-19 with nirmatrelvir-ritonavir to reduce the risk of severe disease and PCC.},
}

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

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

@article {pmid41029812,
year = {2025},
author = {Su, S and Jiang, Z and Shi, L and Liu, X and Zhang, Z and Mei, H and Gao, N and Wu, S and Li, M and Zhang, X and Zhang, A and Tang, C and Zheng, Y and Zhao, Y and Zeng, N and Ni, S and Yan, W and Yuan, K and Sun, Y and Hong, Y and Lu, Y and Shi, J and Bao, Y and Li, X and Lu, L},
title = {Physical, cognitive, and mental health impacts of Omicron reinfection in patients with original SARS-CoV-2 infection: a community-based observational study.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {526},
pmid = {41029812},
issn = {1741-7015},
support = {2021ZD0200700//the National Programs for Brain Science and Brain-like Intelligence Technology of China (STI2030-Major Projects)/ ; 82171514//the National Natural Science Foundation of China/ ; 81761128036//the National Natural Science Foundation of China/ ; 2024YFC2707801//National Key Research and Development Program of China Stem Cell and Translational Research/ ; BMU2022DJXK007//the Fundamental Research Funds for the Central Universities (Peking University Medicine Fund for world's leading discipline or discipline cluster development)/ ; 2021YFC0863700//National Key Research and Development Program of China/ ; 2021ZD0200800//the National Programs for Brain Science and Brain-like Intelligence Technology of China (STI2030-Major Project)/ ; },
mesh = {Humans ; *COVID-19/psychology/epidemiology/complications/physiopathology/virology ; Female ; Male ; Middle Aged ; *Reinfection/psychology/epidemiology ; *SARS-CoV-2 ; Adult ; China/epidemiology ; Aged ; *Mental Health ; },
abstract = {BACKGROUND: Epidemiological and clinical evidence suggests that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reinfection is a complication in a proportion of patients reporting ongoing health issues. However, most studies in the field of SARS-CoV-2 reinfection have focused only on self-reported symptoms and lacked long-term objective measurements. This study aimed to estimate the pattern of chronic symptoms of Omicron reinfection in patients with original SARS-CoV-2 infection by comprehensively assessments 3 years after recovery.

METHODS: This community-based observational study was conducted in Wuhan, China, between January and April in 2023. All participants were recruited from community and invited to participate the interview and examination in a hospital. The subjective multi-system symptoms were self-reported. The objective radiological features and laboratory data were assessed by measuring blood inflammation and performing chest computed tomography (CT) and pulse oxygen saturation.

RESULTS: Among 1438 individuals who participated in the study, 144 were infected with the original variant only in 2020, 980 were Omicron-infected in 2023, 215 were reinfected both in 2020 and 2023, and 99 were never infected. Compared with the non-infection group, the reinfection (odds ratio (OR), 5.15 [95% confidence intervals (CIs), 2.96-8.96]) group was associated with the highest risk of any of chronic physical symptoms, followed by the Omicron infection (3.45 [2.19-5.44]) and original variant infection (2.90 [1.63-5.15]) groups. Compared with the non-infection group, the reinfection (4.05 [2.30-7.14]), Omicron infection (3.72 [2.26-6.11]), and original variant infection (2.71 [1.48-4.95]) groups were associated with an increased risk of any of chronic mental symptoms. Moreover, of all groups, the reinfection group reported the highest seropositivity rate for C-reactive protein, and the highest prevalence rates of ground glass opacities on chest CT and hypoxaemia.

CONCLUSIONS: Our results suggest that reinfection may be a risk factor for long COVID conditions. These findings provide information for the clinical management and healthcare services of long COVID and SARS-CoV-2 reinfection and highlight the importance taking necessary action to prepare for a future pandemic. The long-term follow-up will be needed to verify the impact of different SARS-CoV-2 infection status on long COVID in the future.},
}

Humans
*COVID-19/psychology/epidemiology/complications/physiopathology/virology
Female
Male
Middle Aged
*Reinfection/psychology/epidemiology
*SARS-CoV-2
Adult
China/epidemiology
Aged
*Mental Health

@article {pmid41029414,
year = {2025},
author = {Dempsey, B and Blake, HA and Madan, I and Stevelink, SAM and Greenberg, N and Raine, R and Rafferty, AM and Bhundia, R and Wessely, S and Lamb, D},
title = {COVID-19-related sickness absence among 4,721 NHS staff in England and its relation with long COVID symptoms: findings from NHS CHECK.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {1243},
pmid = {41029414},
issn = {1472-6963},
support = {CF/01/22//Colt Foundation/ ; M952//Rosetrees Trust/ ; MR/V034405/1/MRC_/Medical Research Council/United Kingdom ; ES/V009931/1//Economic and Social Research Council/ ; ISSF3/ H17RCO/C3//UCL/Wellcome/ ; },
}

@article {pmid41029357,
year = {2025},
author = {Dhariwal, R and Thakkar, K and Vaghela, K and Jain, M},
title = {Evaluating post-acute COVID-19 sequelae in younger population using symptom burden questionnaire (SQL).},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3195},
pmid = {41029357},
issn = {1471-2458},
mesh = {Humans ; Female ; *COVID-19/complications/epidemiology/psychology ; Cross-Sectional Studies ; Male ; Young Adult ; Adult ; Adolescent ; Surveys and Questionnaires ; Post-Acute COVID-19 Syndrome ; Anxiety/epidemiology ; Depression/epidemiology ; Prevalence ; Symptom Burden ; },
abstract = {The COVID-19 pandemic, declared by the World Health Organization on March 11, 2020, has led to over 650 million infections globally and a significant burden of long-term health issues, termed post-COVID-19 condition (PCC) or long COVID or post-acute sequelae of COVID-19 (PASC). This cross-sectional study assesses the prevalence and distribution of persistent symptoms among individuals aged 18-25 years using the Symptom Burden Questionnaire™ for Long COVID (SBQ™-LC), which evaluates 123 symptoms across 17 health domains. Our hypothesis interprets that the pandemic has laid mental health challenges among younger populations, evidenced by increased rates of depression and anxiety. Data from participants revealed high rates of mental health issues, sleep disturbances, and cognitive dysfunctions, even among those with mild or asymptomatic infections. Notably, female participants reported higher symptom severity across most domains. This research underscores the necessity for targeted assessments of post-acute sequelae in young adults to enhance understanding and management of long COVID-related health issues.},
}

Humans
Female
*COVID-19/complications/epidemiology/psychology
Cross-Sectional Studies
Male
Young Adult
Adult
Adolescent
Surveys and Questionnaires
Post-Acute COVID-19 Syndrome
Anxiety/epidemiology
Depression/epidemiology
Prevalence
Symptom Burden

@article {pmid41029289,
year = {2025},
author = {Lo, YP and Chiang, SL and Song, CY and Tzeng, WC and Chang, CC and Lin, CH},
title = {Associations between moderate-to-high physical activity levels and long COVID symptoms, heart rate recovery, cardiorespiratory fitness, sleep quality, and quality of life in patients with long COVID: a cross-sectional study.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3204},
pmid = {41029289},
issn = {1471-2458},
support = {TSGH-D-112176//Tri-Service General Hospital/ ; TSGH-E-112249//Tri-Service General Hospital/ ; MND MAB-D-113085//Ministry of National Defense-Medical Affairs Bureau/ ; },
mesh = {Humans ; Cross-Sectional Studies ; *Quality of Life ; Male ; Female ; *COVID-19/physiopathology/complications ; Middle Aged ; *Heart Rate/physiology ; *Cardiorespiratory Fitness/physiology ; *Exercise/physiology ; *Sleep Quality ; Taiwan ; Adult ; Surveys and Questionnaires ; Aged ; },
abstract = {BACKGROUND: Moderate-to-high physical activity (PA) levels have been shown to mitigate health complications, improve cardiovascular health, and enhance patient-reported outcomes, such as sleep quality and quality of life (QoL), among patients with chronic diseases. However, little is known about the associations between moderate-to-high PA levels and long COVID symptoms, heart rate recovery, cardiorespiratory fitness, sleep quality, and QoL among patients with long COVID. This study aimed to examine whether moderate-to-high PA levels are associated with more favorable outcomes in terms of long COVID symptoms, heart rate recovery, cardiorespiratory fitness, and QoL, compared to those with low PA levels.

METHODS: A cross-sectional study was conducted to recruit patients with long COVID (n = 219) from an integrated outpatient clinic for post-COVID-19 at a medical center in northern Taiwan. Eligible participants were categorized into moderate-to-high and low PA groups. PA levels, sleep quality, and QoL were assessed using the International Physical Activity Questionnaire, Pittsburgh Sleep Quality Index, and World Health Organization Quality of Life Questionnaire-short form, respectively. Cardiorespiratory fitness and heart rate recovery were evaluated using cycle ergometer-based graded exercise tests. Multivariate linear and logistic regression models were used to evaluate the associations between PA levels, long COVID symptoms, heart rate recovery, sleep quality, and QoL.

RESULTS: Participants with a mean age of 48.7 years had a mean duration of post-COVID-19 of 12.3 weeks. Patients with moderate-to-high PA levels had a borderline lower risk of shortness of breath (OR = 0.44, p = 0.065), significantly greater VO₂ peak (B = 4.68, p < 0.001) and 2-minute heart rate recovery (B = 3.79, p = 0.049), better sleep quality (B = -1.68, p = 0.007), and higher scores in the physical (B = 0.99, p = 0.023) and psychological (B = 1.11, p = 0.030) domains of QoL, compared to those with lower PA levels.

CONCLUSIONS: Maintaining moderate-to-high PA levels among patients with long COVID may be associated with reduced symptom distress, greater cardiorespiratory fitness and heart rate recovery, and better sleep quality, which are in turn linked to better QoL.

CLINICAL TRIAL NUMBER: not applicable.},
}

Humans
Cross-Sectional Studies
*Quality of Life
Male
Female
*COVID-19/physiopathology/complications
Middle Aged
*Heart Rate/physiology
*Cardiorespiratory Fitness/physiology
*Exercise/physiology
*Sleep Quality
Taiwan
Adult
Surveys and Questionnaires
Aged

@article {pmid41028062,
year = {2025},
author = {Mezache, L and Soltisz, A and Tili, E and Nuovo, GJ and Veeraraghavan, R},
title = {SARS-CoV-2 spike protein-induced inflammation underlies proarrhythmia in COVID-19.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33991},
pmid = {41028062},
issn = {2045-2322},
support = {R01HL148736/HL/NHLBI NIH HHS/United States ; R01HL165751/HL/NHLBI NIH HHS/United States ; R01HL148736/HL/NHLBI NIH HHS/United States ; },
mesh = {*Spike Glycoprotein, Coronavirus/metabolism ; Animals ; *COVID-19/complications/virology/pathology ; *SARS-CoV-2/metabolism ; Connexin 43/metabolism ; Mice ; NAV1.5 Voltage-Gated Sodium Channel/metabolism ; Humans ; *Inflammation/virology ; *Arrhythmias, Cardiac/etiology/virology ; *Atrial Fibrillation/etiology/virology/pathology ; Male ; Mice, Inbred C57BL ; Angiotensin-Converting Enzyme 2/metabolism ; },
abstract = {Coronavirus disease 2019 (COVID-19) patients have a 1.7-fold higher arrhythmia risk with rates of cardiac complications ranging from 2% non-ICU patients to 59% in non-survivors. Atrial fibrillation (AF), the most common arrhythmia, is a frequent complication of acute and long COVID-19. The high expression of ACE2 in the heart suggested that infectious virus may underlie cardiac complications. However, we recently reported in human cardiac tissue from fatal COVID-19 cases perivascular spike protein, elevated pro-inflammatory cytokines, vascular damage, and cardiac remodeling without evidence for direct infection of cardiac cells by SARS-CoV2. Mislocalization of intercalated disc (ID) components, connexin-43 (Cx43) gap junctions and NaV1.5 sodium channels, was also evident in patients' hearts, recapitulating structural remodeling we previously identified as providing a substrate for atrial arrhythmias following an acute inflammatory insult. Therefore, we hypothesized that the inflammatory response elicited by SARS-CoV2 spike protein is sufficient to provoke atrial arrhythmias. Structural and functional assessments of WT murine hearts were performed five days following a single bolus intravenous injection of the viral spike protein. In vivo ECGs demonstrated increased atrial arrhythmia burden in spike-injected mice vs. control. Immunohistochemistry studies revealed elevated expression of inflammatory markers and evidence of vascular damage in these mice. Additionally, we observed disruption of ID ultrastructure and mislocalization of Cx43 and NaV1.5 in the atria of spike protein-injected mice. Our results suggest that vascular-leak inducing inflammatory insult from viral spike protein, and not direct infection by SARS-CoV2 results in the pathophysiology of cardiac dysfunction in fatal COVID-19.},
}

*Spike Glycoprotein, Coronavirus/metabolism
Animals
*COVID-19/complications/virology/pathology
*SARS-CoV-2/metabolism
Connexin 43/metabolism
Mice
NAV1.5 Voltage-Gated Sodium Channel/metabolism
Humans
*Inflammation/virology
*Arrhythmias, Cardiac/etiology/virology
*Atrial Fibrillation/etiology/virology/pathology
Male
Mice, Inbred C57BL
Angiotensin-Converting Enzyme 2/metabolism

@article {pmid41026737,
year = {2025},
author = {Yaker, N},
title = {Performing a Nonsurgical Hair Restoration Consultation.},
journal = {Plastic and aesthetic nursing},
volume = {45},
number = {4},
pages = {228-239},
pmid = {41026737},
issn = {2770-3517},
mesh = {Humans ; *Alopecia/therapy/nursing ; *Referral and Consultation ; COVID-19/complications ; *Hair/growth & development ; },
abstract = {The condition of an individual's skin and hair is an indication of the state of the physiological mechanisms inside their body. Practitioners performing hair restoration consultations should have a clear understanding of the anagen, catagen, and telogen phases of the hair growth cycle and a clear comprehension about the various types and causes of hair loss, including the use of glucagon-like peptide-1 medications and the effects of Long COVID. Nurses can use the Assessment, Diagnosis, Planning, Implementation, and Evaluation nursing process format when providing a professional hair consultation. The goal of this manuscript is to teach aesthetic practitioners how to conduct a thorough nonsurgical hair restoration consultation.},
}

Humans
*Alopecia/therapy/nursing
*Referral and Consultation
COVID-19/complications
*Hair/growth & development

@article {pmid41025260,
year = {2025},
author = {Björnson, M and Wijnbladh, K and Törnberg, A and Svensson-Raskh, A and Svensson, A and Ståhlberg, M and Runold, M and Fedorowski, A and Nygren Bonnier, M and Bruchfeld, J},
title = {Prevalence and Clinical Impact of Postural Orthostatic Tachycardia Syndrome in Highly Symptomatic Long COVID.},
journal = {Circulation. Arrhythmia and electrophysiology},
volume = {},
number = {},
pages = {e013629},
doi = {10.1161/CIRCEP.124.013629},
pmid = {41025260},
issn = {1941-3084},
abstract = {BACKGROUND: The incidence of postural orthostatic tachycardia syndrome (POTS) in long COVID has been a growing concern since the first cases were reported in 2021. The aim of this study was to assess the prevalence and clinical impact of POTS in a series of well-characterized patients with long COVID.

METHODS: We prospectively analyzed 467 nonhospitalized, highly symptomatic (sick leave ≥50%) patients with long COVID, and studied differences in demographics and clinical assessment outcomes between those diagnosed with POTS and the remaining long COVID patients. Examinations were performed at a median of 12 months after acute COVID-19, followed by a cardiologist evaluation with 48-hour ECG, head-up tilt test, and Active Stand Test for those with clinically suspected POTS.

RESULTS: Of all long COVID patients, 143 (31%) were diagnosed with POTS, 128 (27%) did not fulfill POTS criteria, while 196 (42%) had no clinical signs of POTS. Patients with POTS were younger (mean age, 40.0 versus 44.0 versus 47.0 years, respectively; P≤0.001) and predominantly female (91%). They had significantly lower physical activity compared with the other 2 groups, as measured with the Frändin-Grimby scale (P=0.001). Heart rates during the 6-minute walk test were significantly higher in the POTS group, both during walking and at rest afterward, with a significantly shorter walking distance (448 m versus 472 m versus 509 m, respectively; P≤0.001). However, the distribution of symptoms showed no significant differences between the groups.

CONCLUSIONS: In this cohort of predominantly younger women with highly symptomatic long COVID, POTS is common and presents with overlapping symptoms between POTS and non-POTS patients. Long COVID POTS confers lower physical activity and capacity compared with non-POTS long COVID and should be systematically assessed in this condition.},
}

@article {pmid41023887,
year = {2025},
author = {Guillen-Burgos, HF and Sarmiento, M and Gálvez-Flórez, JF and Rojas, C and Lora, YB and Lozada-Martinez, ID and Diazgranados-Garcia, MC and Gibacus, and Rojas, M and Salazar-Uribe, JC and Anaya, JM},
title = {Association between mental health symptoms and autoimmunity in patients with long COVID.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1220},
pmid = {41023887},
issn = {1471-2334},
support = {PCS-MHO-001//Universidad Simon Bolivar/ ; INV-101//COOSALUD EPS/ ; INV-101//COOSALUD EPS/ ; INV-101//COOSALUD EPS/ ; INV-101//COOSALUD EPS/ ; },
mesh = {Humans ; Male ; *COVID-19/psychology/immunology/complications/epidemiology ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; Autoantibodies/blood/immunology ; *Anxiety/immunology/epidemiology ; *Autoimmunity ; Sleep Initiation and Maintenance Disorders/immunology ; *Depression/immunology/epidemiology ; SARS-CoV-2 ; Aged ; Colombia/epidemiology ; Mental Health ; Antibodies, Antinuclear/blood ; },
abstract = {BACKGROUND: Neuropsychiatric symptoms are common features in long COVID. The pathogenesis of neuropsychiatric manifestations in both acute COVID-19 and long COVID remains unclear. This study aimed to examine mental health symptoms-depressive, anxiety, and insomnia symptoms-in COVID-19 survivors with long COVID, and to explore their potential association with autoimmune activity.

METHODS: We conducted an observational, cross-sectional study of 228 adults recruited from a long COVID program in Cartagena, Colombia. Participants underwent clinician-administered interviews and completed validated psychometric scales to assess depressive (PHQ-9), anxiety (GAD-7), and insomnia (ISI) symptoms. Sociodemographic, clinical, and biological data were collected. The autoantibody panel included antinuclear antibodies (ANA), anti-SSA/Ro, anti-SSB/La, anti-RNP, anti-Smith (Sm), rheumatoid factor (RF), anti-thyroglobulin (Tg), and anti-thyroid peroxidase (TPO), measured via ELISA and immunofluorescence. Robust logistic regression models were used to evaluate associations between long COVID, autoantibody positivity, and mental health symptoms, adjusting for age, sex, and relevant covariates.

RESULTS: 57% of participants with a history of COVID-19 acute infection reported long COVID. In participants with long COVID, we reported high proportions of depressive (21.2%), anxiety (31.2%), and insomnia (28.7%) symptoms. Moreover, an association of all three mental health symptoms with autoantibody positivity (particularly antinuclear antibodies [ANA] isolated or co-occurring with anti-TPO antibodies) was observed in individuals with long COVID. Our findings suggest a potential association between psychopathological symptoms, autoantibody positivity, and distinct clinical profiles of long COVID, warranting further longitudinal investigation.

CONCLUSIONS: Mental health symptoms (MHS) should be considered one of the main targets involved in translational research in long COVID. There is an urgent need for consultation-liaison physicians to work closely with immunologists, rheumatologists, and pain medicine physicians in clinical settings as well as in research. This will contribute to a better understanding of the impact of MHS during illness in long COVID variants.},
}

Humans
Male
*COVID-19/psychology/immunology/complications/epidemiology
Female
Middle Aged
Cross-Sectional Studies
Adult
Autoantibodies/blood/immunology
*Anxiety/immunology/epidemiology
*Autoimmunity
Sleep Initiation and Maintenance Disorders/immunology
*Depression/immunology/epidemiology
SARS-CoV-2
Aged
Colombia/epidemiology
Mental Health
Antibodies, Antinuclear/blood

@article {pmid41023255,
year = {2025},
author = {Lee, J and Rojas, NK and Pinto Pereria, SM and Stephenson, T and McGowan, J and Chalder, T and Dalrymple, E and Ford, T and Heyman, I and Ladhani, S and McOwat, K and Simmons, R and Swann, O and , and Shafran, R},
title = {Mental health of children and young people with pre-existing eating problems during the COVID-19 pandemic.},
journal = {Eating and weight disorders : EWD},
volume = {30},
number = {1},
pages = {77},
pmid = {41023255},
issn = {1590-1262},
support = {COVLT0022//National Institute for Health and Care Research/ ; COVLT0022//UK Research and Innovation/ ; MR/P020372/1//UK Medical Research Council Career Development Award/ ; MR/Y009398/1//Senior Non-clinical fellowship/ ; },
mesh = {Humans ; *COVID-19/psychology ; Female ; Child ; *Feeding and Eating Disorders/psychology/epidemiology ; Adolescent ; Male ; *Mental Health ; Retrospective Studies ; Surveys and Questionnaires ; SARS-CoV-2 ; Young Adult ; Pandemics ; },
abstract = {OBJECTIVE: The study sought to explore mental health trajectories of children and young people (CYP) who retrospectively reported eating problems prior to the pandemic, over a 2-year period (2021-23). Given the rapid increase in eating disorder presentations during the pandemic, these CYP may be particularly susceptible to pandemic-related challenges, including social and functional restrictions.

METHODS: Data on 2023 CYP from the Children and Young People with Long COVID (CLoCk) study recruited Jan-March 2021 who completed questionnaires at 3-, 6-, 12-, and 24-months post SARS-CoV-2 PCR-testing were analysed. Associations between baseline eating problems (N = 241) and emotional and behavioural symptoms (measured by the Strengths and Difficulties Questionnaire (SDQ) total difficulties and impact scores) at each time-point were examined by regression models. Multi-level models were used to determine whether SDQ total and impact trajectories of those with/without prior self-reported eating problems differed.

RESULTS: Compared to CYP who did not report pre-existing eating problems, those that did had more mental health difficulties at all time points: reflected in significantly higher SDQ total difficulties and impact scores. However, mental health scores of CYP reporting pre-pandemic eating problems were stable over time. Whereas, CYP without eating problems had a slight increase in mental health difficulties over time. Differences between groups diminished but remained significant when controlling for potential confounding variables including prior mental health difficulties.

DISCUSSION: Young people with eating problems had more emotional and behavioural symptoms during 2021-23, compared with those that did not have eating problems. However, mental health did not worsen over time amongst CYP with pre-existing eating problems, providing evidence of some relative resilience to the effects of the pandemic in this population.

PUBLIC SIGNIFICANCE: Eating disorders are a major public health concern and presentations have remained high since the Covid-19 pandemic. Understanding how eating difficulties relate to mental health symptomology over time has implications for service planning.

LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort study.},
}

Humans
*COVID-19/psychology
Female
Child
*Feeding and Eating Disorders/psychology/epidemiology
Adolescent
Male
*Mental Health
Retrospective Studies
Surveys and Questionnaires
SARS-CoV-2
Young Adult
Pandemics

@article {pmid41021660,
year = {2025},
author = {Carazo, S and Phimmasone, J and Skowronski, DM and Giguère, K and Ouakki, M and Talbot, D and Guay, CA and Sauvageau, C and Brousseau, N and De Serres, G},
title = {Effectiveness of COVID-19 vaccination and prior infections to reduce long COVID risk during the pre-Omicron and Omicron periods.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf549},
pmid = {41021660},
issn = {1537-6591},
abstract = {BACKGROUND: We estimated vaccine effectiveness (VE) against COVID-19 and long COVID during pre-Omicron and Omicron periods, by number of doses and prior infection history.

METHODS: We combined survey information from a cohort of healthcare workers in Quebec, Canada, with immunization registry and laboratory administrative data. We defined COVID-19 cases as symptomatic laboratory-confirmed infections and long COVID as self-reported symptoms persisting ≥12 weeks. We assessed VE against COVID-19 and long COVID, stratified by infection history, using a test-negative design where vaccinated participants were compared to unvaccinated participants during the pre-Omicron period or to those twice vaccinated ≥6 months before laboratory testing during the Omicron period.

RESULTS: Analyses included 8230 COVID-19 participants and 43361 tested specimens. During the pre-Omicron period, one- and two-dose VE was 75% (95%CI:64-83) and 95% (95%CI:84-98) against COVID-19, respectively, and 91% (95%CI:79-96) and 87% (95%CI:22-98) against long COVID, respectively. During the Omicron period, booster dose VE was 41% (95%CI:34-47) against COVID-19 and 57% (95%CI:46-66) against long COVID, waning by 6 months. Hybrid VE in vaccinated and previously infected individuals ranged 81% (95%CI:38-94) to 92% (95%CI:87-95) regardless of number of doses, prior infecting variant or median time since last immunological event up to 9 months.

CONCLUSION: COVID-19 vaccination prevented long COVID during the pre-Omicron period and reduced the risk by more than half post-Omicron. With most of the population by now both vaccinated and infected, repeated booster doses may add little incremental value against long COVID, an observation with important public health, immunization program and cost implications.},
}

@article {pmid41019063,
year = {2025},
author = {Indolfi, C and Klain, A and Dinardo, G and Grella, C and Marrapodi, MM and Miraglia Del Giudice, M},
title = {Commentary: Long COVID in pediatric age: an observational, prospective, longitudinal, multicenter study in Italy.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1624011},
pmid = {41019063},
issn = {1664-3224},
}

@article {pmid41018705,
year = {2025},
author = {Hou, Y and Gu, T and Ni, Z and Shi, X and Ranney, ML and Mukherjee, B},
title = {Global Prevalence of Long COVID, Its Subtypes, and Risk Factors: An Updated Systematic Review and Meta-analysis.},
journal = {Open forum infectious diseases},
volume = {12},
number = {9},
pages = {ofaf533},
pmid = {41018705},
issn = {2328-8957},
abstract = {BACKGROUND: This mega-systematic review evaluated the global prevalence of long COVID and its subtypes and symptoms, and assessed the effects of risk factors for long COVID.

METHODS: Studies published from 5 July 2021 to 29 May 2024 were searched in PubMed, Embase, and Web of Science, with supplemental updates on 23 July 2024. Data were pooled using a random-effects framework with DerSimonian-Laird estimator. Risk of bias analysis was conducted.

RESULTS: A total of 429 studies were meta-analyzed. The global pooled long COVID prevalence was 36% (95% confidence interval [CI], 33%-40%) with 144 contributing studies. The highest prevalence rates were observed in South America (51% [95% CI, 35%-66%]). The prevalence of long COVID persisted over time, with 35% (95% CI, 31%-39%) at <1 year of follow-up and 46% (95% CI, 37%-57%) at 1-2 years. The most prevalent subtypes were respiratory (20% [95% CI, 14%-28%]) estimated from 31 studies, general fatigue (20% [95% CI, 18%-23%]) from 119 studies, psychological (18% [95% CI, 11%-28%]) from 10 studies, and neurological (16% [95% CI, 8%-30%]) from 23 studies. The 3 strongest risk factors were being unvaccinated for COVID-19 (pooled odds ratio [OR], 2.09 [95% CI, 1.55-2.81]) meta-analyzed from 7 studies, infections from pre-Omicron variants (OR, 1.74 [95% CI, 1.40-2.17]) from 6 studies, and female sex (OR, 1.56 [95% CI, 1.32-1.84]) from 33 studies.

CONCLUSIONS: Long COVID is globally prevalent after a severe acute respiratory syndrome coronavirus 2 infection, highlighting a continuing health challenge. The heterogeneity of estimates across populations argues the need for well-designed follow-up studies that use consistent measures and are globally representative.},
}

@article {pmid41018694,
year = {2025},
author = {de Lemos Muller, CH and Pohl, HH and Reckziegel, MB},
title = {Prevalence and clinical profile of COVID-19 among farmworkers from the interior of the state of Rio Grande do Sul, Brazil.},
journal = {Revista brasileira de medicina do trabalho : publicacao oficial da Associacao Nacional de Medicina do Trabalho-ANAMT},
volume = {23},
number = {3},
pages = {e20251444},
pmid = {41018694},
issn = {1679-4435},
abstract = {INTRODUCTION: Farmworkers in Brazil face poor living conditions, limited healthcare access, and high prevalence of chronic diseases. These vulnerabilities may increase COVID-19 risk, complications, and persistent symptoms, underscoring the importance of characterizing the disease's impact in this population.

OBJECTIVES: To identify the prevalence and clinical profile of COVID-19 among farmworkers of cities that participate of the Conselho Regional de Desenvolvimento do Vale do Rio Pardo.

METHODS: A retrospective cross-sectional study that utilized a database from a research performed with rural workers of cities from Conselho Regional de Desenvolvimento do Vale do Rio Pardo. Hundred seven volunteers were included (54.01 ± 13.02 years) who answered the questionnaries of life style and COVID-19, in addition to having performed body composition assessment. Prevalence ratio was measured to verify association between risk factors and COVID-19 diagnosis.

RESULTS: Twenty-five people (23.36%) were diagnosticated with COVID-19. The more described symptoms were fatigue (84%), fever (68%), cough (68%), loss of taste (68%), headache (68%), and sore throat (64%). None of the participants was hospitalized. Symptoms of long covid were observed in 52% participants, with fatigue (24%) and breathless (16%) being the most prevalent. The results showed positive association between COVID-19 diagnosis and hypertension (prevalence ratio 1.23), cancer (prevalence ratio 1.22) and obesity (prevalence ratio 1.76).

CONCLUSIONS: The results help to characterize the clinical profile of the disease in a population with less access to health services.},
}

@article {pmid41017688,
year = {2025},
author = {Mahoney, J and Shatri, G and Simmer, PE and Doherty, D and Matta, V and Valentino, DJ},
title = {Retrospective analysis of patients with cardiopulmonary symptoms in the setting of Long COVID syndrome: investigating risk factors.},
journal = {Journal of osteopathic medicine},
volume = {},
number = {},
pages = {},
pmid = {41017688},
issn = {2702-3648},
abstract = {CONTEXT: Long COVID, a debilitating condition characterized by persistent symptoms following acute Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, continues to pose a significant public health burden. Currently, research is ongoing regarding risk factors for developing Long COVID. Identifying patients susceptible to symptoms of Long COVID can assist with identifying those at risk, and developing preventative strategies for these individuals.

OBJECTIVES: The objectives of this study are to evaluate a cohort of patients who followed up in the Long COVID clinic who were experiencing cardiopulmonary symptoms 8-12 weeks from initial inoculation, and to retrospectively identify any statistically significant risk factors or clinical features present.

METHODS: This retrospective cohort study examined patients identified between April 2021 and September 2022. Patients who were diagnosed with COVID-19 and developed persistent symptoms were subsequently referred to the post-COVID-19 pulmonary clinic. For the cohort of patients seen in post COVID-19 pulmonary clinic, pre-existing pulmonary and systemic disease, severity of COVID-19 illness, and treatments received were examined. Analysis was performed on these data utilizing Cox regression analysis.

RESULTS: Two hundred forty-six (246) adult patients who had Long COVID symptoms 8-12 weeks post-COVID-19 infection were identified and included in this analysis. Cox regression analysis indicated that in this population, patients who had required oxygen support (supplemental oxygen, noninvasive ventilation, or intubation) during their initial COVID-19 hospitalization and who also had prior history of either obstructive sleep apnea (OSA) or chronic obstructive pulmonary disease (COPD) and were more likely to develop Long COVID symptoms. Patients with pre-existing OSA had an odds ratio (OR) of 3.6 and a 95 % confidence interval (CI) of 1.70-7.65 (p=0.0012). Patients with pre-existing COPD had an OR of 12.19 and a 95 % CI of 2.38-62.33 (p=0.0015).

CONCLUSIONS: Patients who required oxygen support during their initial COVID-19 hospitalization who also had previous history of either OSA or COPD were more likely to develop cardiopulmonary Long COVID symptoms. This suggests that pre-existing respiratory conditions and the severity of the initial COVID-19 illness may influence the development of these symptoms of Long COVID.},
}

@article {pmid41013344,
year = {2025},
author = {Nji, MAM and Briones, EM and Issa, A and Tierney, M and Bertolli, J and Barshikar, S and Unger, ER and Wisnivesky, J and Vu, Q and Quimby, D and Abrams, J and Jagan, N and Manouchehripour, S and Laguerre, M and Cope, JR},
title = {Medical complexity and healthcare utilization among patients attending three U.S. post-COVID clinics.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {1145},
pmid = {41013344},
issn = {1471-2334},
mesh = {Humans ; Female ; Middle Aged ; Male ; *COVID-19/epidemiology/therapy ; Adult ; Aged ; Retrospective Studies ; Aged, 80 and over ; Adolescent ; Young Adult ; *Patient Acceptance of Health Care/statistics & numerical data ; SARS-CoV-2 ; United States/epidemiology ; Texas/epidemiology ; },
abstract = {BACKGROUND: Patients who do not fully recover or develop new symptoms following SARS-CoV-2 infection require follow-up and sometimes seek care at specialized multidisciplinary care clinics. We aimed to describe the clinical characteristics and care needs of patients at three such post-COVID clinics.

METHODS: We conducted a multisite retrospective electronic chart review of 984 patients, aged ≥ 18 years, who visited one of three post-COVID clinics at least 28 days after a clinical or polymerase chain reaction (PCR)-confirmed diagnosis of SARS-CoV-2 infection between January 20, 2020, and March 31, 2021. The clinics were located in Omaha, Nebraska, New York City, New York, and Dallas, Texas. Patient records were obtained through September 30, 2021. Data on clinical evaluations and healthcare provider visits were abstracted by trained clinical personnel using a standardized health record abstraction tool.

RESULTS: The median age was 52 years (range 18-89 years), 59.9% were female, and 69.0% were White. Of 984 patients, 79.9% had SARS-CoV-2 infection that was confirmed by PCR, 32.1% had three or more comorbid conditions, and 39.4% had been hospitalized. During post-COVID follow-up, the most common symptoms were shortness of breath (59.2%), post-exertional malaise (45.6%), fatigue (43.2%), and brain fog (42.8%). Nearly one in three patients had a diagnosis of post-viral fatigue syndrome (30.1%), and pulmonary system conditions (24.4%) were also common. Overall, the 984 participants attended 3914 visits (median 3; range 1-46) over a median follow-up period of 107 days (range 1-560) between first and last post-COVID follow-up visits. Of the 984 patients, 64.3% were referred for subspecialty care notably pulmonology, cardiology, and neurology. More than a third of patients were referred for rehabilitation therapy (37.9%) including physical, occupational, speech, and psychotherapy.

CONCLUSION: Adult patients at post-COVID clinics have a wide range of symptoms and conditions that highlight the medical complexity of these patients and their need for high levels of care, including multiple health care visits and referrals for therapy. This underscores the need for well-coordinated, multidisciplinary care, and planning of health resources for post-COVID-19 follow-up care.},
}

Humans
Female
Middle Aged
Male
*COVID-19/epidemiology/therapy
Adult
Aged
Retrospective Studies
Aged, 80 and over
Adolescent
Young Adult
*Patient Acceptance of Health Care/statistics & numerical data
SARS-CoV-2
United States/epidemiology
Texas/epidemiology

@article {pmid41012643,
year = {2025},
author = {Yang, YF and Ling, MP and Chen, SC and Lin, YJ and You, SH and Lu, TH and Chen, CY and Wang, WM and Chen, SY and Lai, IH and Hsiao, HA and Liao, CM},
title = {Biomarker-Based Risk Assessment Strategy for Long COVID: Leveraging Spike Protein and Proinflammatory Mediators to Inform Broader Postinfection Sequelae.},
journal = {Viruses},
volume = {17},
number = {9},
pages = {},
doi = {10.3390/v17091215},
pmid = {41012643},
issn = {1999-4915},
support = {NSTC 113-2313-B-002-032//National Science and Technology Council/ ; },
mesh = {Humans ; *Spike Glycoprotein, Coronavirus/metabolism/blood ; *COVID-19/diagnosis/virology/immunology ; *Biomarkers/blood ; Risk Assessment ; SARS-CoV-2 ; Male ; Middle Aged ; Female ; Models, Theoretical ; Interleukin-6/blood ; *Inflammation Mediators/blood ; Cytokines/blood ; Post-Acute COVID-19 Syndrome ; Interleukin-8/blood ; Tumor Necrosis Factor-alpha/blood ; Aged ; Adult ; },
abstract = {Long COVID, characterized by persistent symptoms following acute SARS-CoV-2 infection, has emerged as a significant public health challenge with wide-ranging clinical and socioeconomic implications. Developing an effective risk assessment strategy is essential for the early identification and management of individuals susceptible to prolonged symptoms. This study uses a quantitative approach to characterize the dose-response relationships between spike protein concentrations and effects, including Long COVID symptom numbers and the release of proinflammatory mediators. A mathematical model is also developed to describe the time-dependent change in spike protein concentrations post diagnosis in twelve Long COVID patients with a cluster analysis. Based on the spike protein concentration-Long COVID symptom numbers relationship, we estimated a maximum symptom number (~20) that can be used to reflect a persistent predictor. We found that among the crucial biomarkers associated with Long COVID proinflammatory mediator, CXCL8 has the lowest 50% effective dose (0.01 μg mL[-1]), followed by IL-6 (0.39), IL-1β (0.46), and TNF-α (0.56). This work provides a comprehensive risk assessment strategy with dose-response tools and mathematical modeling developed to estimate potential spike protein concentration. Our study suggests persistent Long COVID guidelines for personalized care strategies and could inform public health policies to support early interventions that reduce long-term disability and healthcare burdens with possible other post-infection syndromes.},
}

Humans
*Spike Glycoprotein, Coronavirus/metabolism/blood
*COVID-19/diagnosis/virology/immunology
*Biomarkers/blood
Risk Assessment
SARS-CoV-2
Male
Middle Aged
Female
Models, Theoretical
Interleukin-6/blood
*Inflammation Mediators/blood
Cytokines/blood
Post-Acute COVID-19 Syndrome
Interleukin-8/blood
Tumor Necrosis Factor-alpha/blood
Aged
Adult

@article {pmid41012598,
year = {2025},
author = {Khaidarov, S and Hejran, AB and Moldakaryzova, A and Izmailova, S and Nurgaliyeva, B and Beisenova, A and Mustafaeva, A and Nurzhanova, K and Belova, Y and Satbayeva, E and Aidarov, A and Ossikbayeva, S and Kukubassov, Y and Amankulov, J and Goncharova, T and Yeszhan, B and Tulman, E and Tazhibayeva, KN and Sadykova, A and Kozhabergenov, N and Burashev, Y},
title = {An Anti-HIV Drug Is Highly Effective Against SARS-CoV-2 In Vitro and Has Potential Benefit for Long COVID Treatment.},
journal = {Viruses},
volume = {17},
number = {9},
pages = {},
doi = {10.3390/v17091170},
pmid = {41012598},
issn = {1999-4915},
mesh = {*SARS-CoV-2/drug effects ; Chlorocebus aethiops ; Vero Cells ; Animals ; *COVID-19 Drug Treatment ; *Tenofovir/pharmacology/analogs & derivatives ; *Antiviral Agents/pharmacology ; Humans ; Viral Load/drug effects ; Alanine ; *Anti-HIV Agents/pharmacology ; COVID-19/virology ; *Adenine/analogs & derivatives/pharmacology ; Drug Repositioning ; Virus Replication/drug effects ; },
abstract = {The persistent evolution of SARS-CoV-2 necessitates novel antiviral strategies. This study evaluated the anti-HIV prodrugs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) for repurposing against SARS-CoV-2, assessing key pharmacological indices (CC50, EC50, cytostatic effect, and therapeutic window). In vitro screening in Vero E6 cells measured cytotoxicity (via CCK-8/MTT assays) and antiviral activity against Kazakh B.1 and Wuhan strains. TDF (50 µg/mL) reduced high viral loads (MOI 2) by ~2 log10 (100% inhibition), with minimal cytotoxicity (≥75% viability). TAF achieved near-complete suppression (100% inhibition) at 50 µg/mL, exhibiting dose-dependent inhibition (68-100%) at lower viral loads (MOI 0.01). Both prodrugs showed enhanced antiviral activity with prolonged exposure (96 h). Synergy assessments demonstrated favourable combination indices (CI < 1). Electron microscopy confirmed virion integrity post-treatment. These findings highlight TDF and TAF as promising candidates against SARS-CoV-2, with particular potential for targeting lymphoid reservoirs-sites implicated in persistent viral reservoirs that may contribute to long COVID pathogenesis. Further clinical validation is warranted.},
}

*SARS-CoV-2/drug effects
Chlorocebus aethiops
Vero Cells
Animals
*COVID-19 Drug Treatment
*Tenofovir/pharmacology/analogs & derivatives
*Antiviral Agents/pharmacology
Humans
Viral Load/drug effects
Alanine
*Anti-HIV Agents/pharmacology
COVID-19/virology
*Adenine/analogs & derivatives/pharmacology
Drug Repositioning
Virus Replication/drug effects

@article {pmid41012111,
year = {2025},
author = {Arévalo-Genicio, A and García-Arqué, MC and Gragea-Nocete, M and Llistosella, M and Moro-Casasola, V and Pérez-Díaz, C and Puigdellívol-Sánchez, A and Roca-Puig, R},
title = {Long COVID Syndrome Prevalence in 2025 in an Integral Healthcare Consortium in the Metropolitan Area of Barcelona: Persistent and Transient Symptoms.},
journal = {Vaccines},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/vaccines13090905},
pmid = {41012111},
issn = {2076-393X},
support = {PT-082023-EP subproject COVID-P//Government of Catalonia/ ; },
abstract = {BACKGROUND: Long COVID can persist for years, but little is known about its prevalence in relation to the number of infections. This study examines the prevalence of long COVID in association with the number of infections and vaccination status.

METHODS: We analyzed anonymized data on long COVID cases, thrombotic events and polypharmacy from March 2020, provided by the Data Analysis Control Department for the population assigned to the CST (192,651 at March 2025). Additionally, we analyzed responses to a long COVID symptom-specific survey distributed in March 2024 to individuals aged 18 to 75 years from the CST population diagnosed with COVID-19 as of December 2023 (n = 43,398; 3227 respondents). Symptomatic patients suspected of having long COVID underwent blood tests to exclude alternative diagnoses.

RESULTS: The overall detected prevalence of long COVID was 2.4‱, with higher frequency among women aged 30-59 years (p < 0.001). The survey, combined with specific blood tests, improved detection rates by 26.3%. Long COVID prevalence was 3-10 times higher in individuals with three or more infections than in those with only one recorded infection (based on survey/CST data, respectively). The absolute number of thrombotic events among individuals aged >60 doubled from 2020 to 2024, occurring in both vaccinated and unvaccinated individuals, as well as in those with or without prior documented COVID-19 infection, including in patients without chronic treatments.

CONCLUSIONS: We found a link between SARS-CoV-2 reinfection and long COVID, and a post-pandemic rise in thrombotic events across all populations, regardless of vaccination or prior infection. Findings support continued COVID-19 diagnosis in suspected cases and mask use by healthcare workers treating respiratory patients.},
}

@article {pmid41012107,
year = {2025},
author = {Shakib, SH and Karimi, SM and McGeeney, JD and Parh, MYA and Zarei, H and Chen, Y and Goldman, B and Novario, D and Schurfranz, M and Warren, CA and Antimisiaris, D and Little, BB and McKinney, WP and Graham, AJ},
title = {Local Health Department COVID-19 Vaccination Efforts and Associated Outcomes: Evidence from Jefferson County, Kentucky.},
journal = {Vaccines},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/vaccines13090901},
pmid = {41012107},
issn = {2076-393X},
support = {OGMB220965A//American Rescue Fund/ ; OGMB220965B//Centers for Disease Control and Prevention (CDC)/ ; },
abstract = {Background: While disparities in vaccine uptake have been well documented, few studies have evaluated the impact of local vaccine programs on COVID-19 outcomes, namely cases, hospitalizations, and deaths. Objectives: Evaluate the impact of COVID-19 vaccine doses coordinated by the Louisville Metro Department of Public Health and Wellness (LMPHW) on COVID-19 outcomes by race across ZIP codes from December 2020 to May 2022 in Jefferson County, Kentucky. Methods: Fixed-effects longitudinal models with ZIP codes as ecological time-series units were estimated to measure the association between COVID-19 vaccine doses and outcomes with time lags of one week, two weeks, three weeks, four weeks, and one month. Models were adjusted for time (week or month of the year) and its interaction with ZIP code. Results: In the one-week lag model, significant negative associations were observed between LMPHW-coordinated vaccine doses and COVID-19 outcomes, indicating reductions of 11.6 cases, 0.4 hospitalizations, and 0.3 deaths per 100 doses administered. Vaccine doses were consistently associated with fewer deaths among White residents across all lags, with an average reduction of 0.2 deaths per 100 doses. No significant associations were found for Black residents. Temporal trends also indicated declines in COVID-19 outcomes when LMPHW's vaccine administration program peaked, between March and May 2021. Conclusions: Timely uptake of COVID-19 vaccines remains critical in avoiding severe outcomes, especially with emerging variants. Racial disparities in vaccine-outcome associations emphasize the potential need for equitable, community-driven vaccine campaigns to improve population health outcomes.},
}

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

@article {pmid41011472,
year = {2025},
author = {Rescalvo-Casas, C and Fernández-Villegas, R and Hernando-Gozalo, M and Seijas-Pereda, L and Lledó García, L and Arendt-Nielsen, L and Cuadros-González, J and Pérez-Tanoira, R},
title = {A Retrospective Study on Coinfections, Antimicrobial Resistance, and Mortality Risk Among COVID-19 Patients (2020-2021) with Consideration of Long-COVID Outcomes.},
journal = {Microorganisms},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/microorganisms13092141},
pmid = {41011472},
issn = {2076-2607},
abstract = {Coinfections in COVID-19 patients can worsen disease severity by enhancing SARS-CoV-2 replication and proinflammatory cytokine levels. This study analyzes the characteristics of coinfected COVID-19 patients across the pandemic and their association with in-hospital mortality. We retrospectively examined data from 351 COVID-19 patients hospitalized in a Spanish secondary hospital between March 2020 and February-March 2021. Nasopharyngeal swabs from 340 patients were analyzed using multiplex RT-PCR to identify 26 respiratory pathogens. A total of 136 patients were coinfected with 191 bacteria (100 Gram-negative and 91 Gram-positive), 20 viruses, 18 fungi, and 1 protist. In 2021, empirical cephalosporin use increased (p = 0.009). The incidence of enterococcal coinfections tripled from 2020 to 2021 (p < 0.001). In 2021, a greater proportion of patients experienced urine (p = 0.001) and bloodstream (p = 0.010) coinfections. In 2020, there was one bloodstream infection, while in 2021, there were seven, with half of them being fatal. Coinfected patients experienced longer hospital stays and higher odds of long COVID (p < 0.001; p = 0.014; p = 0.045). Non-respiratory coinfections in 2021 correlated with increased mortality (p = 0.002). Antimicrobial resistance remained stable (p = 0.149). The rise in cephalosporin use correlated with increased Enterococcus infections, notably bloodstream infections, which were linked to mortality (p = 0.016). In 2021, coinfections were linked to prolonged hospital stays and an increased risk of mortality in our patient cohort.},
}

@article {pmid41011077,
year = {2025},
author = {Onik, G and Sieroń, K},
title = {Longer Health Resort Therapy Improves Outcomes in Long COVID: A Retrospective Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {9},
pages = {},
doi = {10.3390/medicina61091686},
pmid = {41011077},
issn = {1648-9144},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; *COVID-19/therapy/complications/physiopathology ; *Health Resorts/statistics & numerical data ; Aged ; Treatment Outcome ; Severity of Illness Index ; SARS-CoV-2 ; Time Factors ; },
abstract = {Background and Objectives: The positive effect of health resort treatment on long COVID symptoms has been demonstrated. However, no previous study has considered therapy duration as a factor determining treatment effectiveness. Therefore, the objective of this study was to determine whether the duration of treatment predicts its effectiveness in individuals with long COVID. Materials and Methods: In this retrospective study, medical records of 119 individuals (68 women and 51 men; mean age 63.04 ± 8.61 years) undergoing health resort treatment for long COVID were analyzed. Participants were divided into two groups based on therapy duration: shorter (Group 1) and prolonged (Group 2). Dyspnea was assessed using the mMRC scale, physical performance with the SPPB, and functional status with the PCFS scale. Additionally, individuals rated symptom severity on 0-10 point scales. Results: Improvement in functional status was greater in individuals with a prolonged stay at the health resort (Group 1: 0.59 ± 0.66 points; Group 2: 1.41 ± 0.65 points; p < 0.001). Changes in the severity of most long COVID symptoms were significantly greater in patients who stayed longer. An extended stay at the health resort was associated with significant improvement in functional status (β = 0.033, p = 0.003) and in most long COVID symptoms, particularly sleep disorders (β = 0.112, p < 0.0001), memory disorders (β = 0.104, p < 0.0001), and headaches (β = 0.103, p < 0.0001). Conclusions: A prolonged stay in a sanatorium exerts a favorable effect on symptom severity in individuals with long COVID. Comprehensive health resort treatment of approximately four weeks is associated with improved functional status and alleviation of neuropsychiatric symptoms. Nevertheless, given the retrospective design of the present study, prospective research is required to validate these findings.},
}

Humans
Retrospective Studies
Male
Female
Middle Aged
*COVID-19/therapy/complications/physiopathology
*Health Resorts/statistics & numerical data
Aged
Treatment Outcome
Severity of Illness Index
SARS-CoV-2
Time Factors

@article {pmid41010719,
year = {2025},
author = {Popa, DI and Buleu, F and Iancu, A and Tudor, A and Williams, CG and Militaru, M and Levai, CM and Buleu, T and Ciolac, L and Militaru, AG and Mederle, OA},
title = {Long COVID and Acute Stroke in the Emergency Department: An Analysis of Presentation, Reperfusion Treatment, and Early Outcomes.},
journal = {Journal of clinical medicine},
volume = {14},
number = {18},
pages = {},
doi = {10.3390/jcm14186514},
pmid = {41010719},
issn = {2077-0383},
support = {Victor Babes University of Medicine and Pharmacy, Timisoara//Victor Babes University of Medicine and Pharmacy, Timisoara/ ; },
abstract = {Background and Objectives: Long COVID has been linked with persistent neurological symptoms, but data on its effects on acute stroke presentation, management, and outcomes remain unclear. This study aimed to compare the clinical profile, management, and short-term outcome of acute ischemic stroke patients with and without Long COVID. Materials and Methods: A retrospective cohort study was conducted on 132 patients who presented at admission with code stroke alert in our Emergency Department (ED). Out of those, 26 were identified to have the Long COVID condition and assigned to the Long COVID group, and 106 were without the Long COVID condition and assigned to the No Long COVID group. Baseline demographics, stroke severity by NIHSS (National Institutes of Health Stroke Scale), risk factors, admission symptoms, laboratory findings, Emergency department time targets, reperfusion treatments received, and outcomes between the two groups were compared. Results: There were no significant differences between the two groups in age, gender, baseline NIHSS scores, ED time targets, or laboratory values. The proportion of patients with Long COVID significantly increased among non-smokers (Fisher's Exact Test chi-squared, p = 0.027). Also, patients suffering from Long COVID exhibited higher incidences of headache (19.2% compared to 5.7%, OR = 3.97, p = 0.040) and facial drooping (42.3% compared to 19.8%, OR = 2.97, p = 0.022). The mechanical thrombectomy was more frequent among the group with Long COVID (30.8% vs. 16.0%), but this difference was not statistically significant. More hemorrhagic transformations happened in the Long COVID group (26.9% vs. 14.2%, p = 0.143). Discharge rates and hospital length of stay in days were similar between groups. Conclusions: Long COVID patients did not present notable differences in emergency department time targets, baseline stroke severity, or short-term outcomes when presenting with code stroke alert. Nevertheless, specific clinical characteristics-such as elevated occurrences of headache and facial drooping-were more frequently observed in patients with Long COVID, alongside non-significant trends indicating a greater utilization of mechanical thrombectomy and increased rates of hemorrhagic transformation. These results imply that Long COVID may have a subtle impact on stroke presentation and potentially on underlying cerebrovascular susceptibility. Further prospective studies with larger sample sizes are necessary to investigate Long COVID's long-term neurological and vascular consequences.},
}

@article {pmid41009814,
year = {2025},
author = {Polo-Alonso, S and Hernáez, Á and Dégano, IR and Martí-Lluch, R and Pinsach-Abuin, ML and Elosua, R and Subirana, I and Puigmulé, M and Pérez, A and Cruz, R and Diz-de Almeida, S and Puigdecant, E and Selga, E and Nogues, X and Masclans, JR and Güerri-Fernández, R and Cubero-Gallego, H and Tizon-Marcos, H and Vaquerizo, B and Brugada, R and Ramos, R and Camps-Vilaró, A and Marrugat, J},
title = {Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall.},
journal = {International journal of molecular sciences},
volume = {26},
number = {18},
pages = {},
doi = {10.3390/ijms26189252},
pmid = {41009814},
issn = {1422-0067},
support = {CB16/11/00229 and CB16/11/00246//CIBER - Consorcio Centro de Investigación Biomédica en Red/ ; 2021SGR144//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; //Crue-CSIC-Santander FONDO SUPERA COVID-19/ ; 202119-30//Fundació La Marató de TV3/ ; },
mesh = {Humans ; *Genome-Wide Association Study ; *COVID-19/genetics/epidemiology ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Sex Factors ; Polymorphism, Single Nucleotide ; Aged ; Adult ; Genetic Predisposition to Disease ; Post-Acute COVID-19 Syndrome ; Cohort Studies ; },
abstract = {We aimed to explore the global and sex-specific genetic variants associated with long COVID, as defined by patient-driven symptom recall. A 1-year cohort study of 2411 COVID-19 patients collected long COVID symptoms with an open-ended, non-directed questionnaire, and long COVID incidence was determined according to the World Health Organization definition. Global and sex-stratified genome-wide association analyses were conducted by logistic regression models adjusted for age, sex (in the global analysis), and the first 10 principal components. We assessed sex-variant interactions and performed gene-based analyses, gene mapping, and gene-set enrichment analyses. When comparing the 1392 long COVID cases with the non-cases, we identified 23 lead variants from suggestive signals: 13 from the global analysis, 5 from females, and 5 from males. Five variants showed a significant interaction with sex (two in females, three in males). We mapped 15 protein-coding genes related to diseases of the immune and nervous systems and tumoral processes. Notably, CD5 and VPS37C, linked to immune function, were significantly associated with long COVID in men. Our results suggest that persistent immune dysregulation may be involved in the development of precisely defined long COVID.},
}

Humans
*Genome-Wide Association Study
*COVID-19/genetics/epidemiology
Male
Female
Middle Aged
SARS-CoV-2
Sex Factors
Polymorphism, Single Nucleotide
Aged
Adult
Genetic Predisposition to Disease
Post-Acute COVID-19 Syndrome
Cohort Studies

@article {pmid41009651,
year = {2025},
author = {Santinelli, L and Gentilini Cacciola, E and Bortolani, L and Ridolfi, M and Maddaloni, L and Frasca, F and Fracella, M and Bugani, G and d'Ettorre, G and Mastroianni, CM and Ceccarelli, G and d'Ettorre, G},
title = {Long COVID and Type I IFN Signature in Working-Age Adults: A Cross-Sectional Study.},
journal = {International journal of molecular sciences},
volume = {26},
number = {18},
pages = {},
doi = {10.3390/ijms26189089},
pmid = {41009651},
issn = {1422-0067},
support = {The NextGeneration EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseas-es (Project no. PE00000007, INF-ACT).//EU/ ; },
mesh = {Humans ; *COVID-19/immunology/genetics/blood/virology ; Cross-Sectional Studies ; Adult ; Female ; Male ; SARS-CoV-2 ; Middle Aged ; Cytokines/genetics ; Interferon-beta/genetics/blood ; *Interferon Type I/genetics/blood ; Biomarkers/blood ; Ubiquitins/genetics ; Interferon-alpha/genetics/blood ; Post-Acute COVID-19 Syndrome ; },
abstract = {To investigate relevant biomarkers that might aid in the diagnosis and monitoring of long COVID (LC), an analysis of IFN-α, IFN-β, ISG15, and ISG56 transcripts was performed by Real-Time PCR among people of working age who had been infected with SARS-CoV-2 one year prior to the study [LC and non-long COVID (NLC)]. Despite no differences in the transcript levels of IFN-α, IFN-β, ISG15, and ISG56 between LC and NLC, higher IFN-β mRNA levels were observed among LC compared to NLC individuals who were hospitalized for more than 10 days during acute SARS-CoV-2 infection. Moreover, previously SARS-CoV-2 infected participants that did not require respiratory support and developed LC exhibited higher levels of IFN-α and IFN-β compared to NLC with the same clinical characteristics. These results highlight that SARS-CoV-2 infection leads to changes in peripheral innate immune pathways, which could have implications for the development of LC.},
}

Humans
*COVID-19/immunology/genetics/blood/virology
Cross-Sectional Studies
Adult
Female
Male
SARS-CoV-2
Middle Aged
Cytokines/genetics
Interferon-beta/genetics/blood
*Interferon Type I/genetics/blood
Biomarkers/blood
Ubiquitins/genetics
Interferon-alpha/genetics/blood
Post-Acute COVID-19 Syndrome

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

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

@article {pmid41008975,
year = {2025},
author = {Mese, O and Otsuka, Y and Sakurada, Y and Tokumasu, K and Soejima, Y and Morita, S and Nakano, Y and Honda, H and Eguchi, A and Fukuda, S and Nojima, J and Otsuka, F},
title = {Clinical Evaluation of Oxidative Stress Markers in Patients with Long COVID During the Omicron Phase in Japan.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/antiox14091068},
pmid = {41008975},
issn = {2076-3921},
support = {2024//Research grant from the Japanese Society of Hospital General Medicine/ ; 23fk0108585h0001, 24lk0310100h0001//Japan Agency for Medical Research and Development/ ; },
abstract = {To characterize changes in markers of oxidative stress for the clinical evaluation of patients with long COVID, we assessed oxidative stress and antioxidant activity based on serum samples from patients who visited our clinic between May and November 2024. Seventy-seven patients with long COVID (41 [53%] females and 36 [47%] males; median age, 44 years) were included. Median [interquartile range] serum levels of diacron-reactive oxygen metabolites (d-ROM; CARR Unit), biological antioxidant potential (BAP; μmol/L), and oxidative stress index (OSI) were 533.8 [454.9-627.6], 2385.8 [2169.2-2558.1] and 2.0 [1.7-2.5], respectively. Levels of d-ROMs (579.8 vs. 462.2) and OSI (2.3 vs. 1.8), but not BAP (2403.4 vs. 2352.6), were significantly higher in females than in males. OSI levels positively correlated with age and body mass index, whereas BAP levels negatively correlated with these parameters. d-ROM and OSI levels were significantly associated with inflammatory markers, including C-reactive protein (CRP) and fibrinogen, whereas BAP levels were inversely correlated with CRP and ferritin levels. Notably, serum free thyroxine levels were negatively correlated with d-ROMs and OSI, whereas cortisol levels were positively correlated with d-ROMs. Among long COVID symptoms, patients reporting brain fog exhibited significantly higher OSI levels (2.2 vs. 1.8), particularly among females (d-ROMs: 625.6 vs. 513.0; OSI: 2.4 vs. 2.0). The optimal OSI cut-off values were determined to be 1.32 for distinguishing long COVID from healthy controls and 1.92 for identifying brain fog among patients with long COVID. These findings suggest that oxidative stress markers may serve as indicators for the presence or prediction of psycho-neurological symptoms associated with long COVID in a gender-dependent manner.},
}

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

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

@article {pmid41008398,
year = {2025},
author = {Popa, MV and Buzea, CG and Gurzu, IL and Salim, C and Gurzu, B and Rusu, DI and Ochiuz, L and Duceac, LD},
title = {An Integrated AI Framework for Occupational Health: Predicting Burnout, Long COVID, and Extended Sick Leave in Healthcare Workers.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {18},
pages = {},
doi = {10.3390/healthcare13182266},
pmid = {41008398},
issn = {2227-9032},
abstract = {BACKGROUND: Healthcare workers face multiple, interlinked occupational health risks-burnout, post-COVID-19 sequelae (Long COVID), and extended medical leave. These outcomes often share predictors, contribute to each other, and, together, impact workforce capacity. Yet, existing tools typically address them in isolation.

OBJECTIVE: The objective of this study to develop and deploy an integrated, explainable artificial intelligence (AI) framework that predicts these three outcomes using the same structured occupational health dataset, enabling unified workforce risk monitoring.

METHODS: We analyzed data from 1244 Romanian healthcare professionals with 14 demographic, occupational, lifestyle, and comorbidity features. For each outcome, we trained a separate predictive model within a common framework: (1) a lightweight transformer neural network with hyperparameter optimization, (2) a transformer with multi-head attention, and (3) a stacked ensemble combining transformer, XGBoost, and logistic regression. The data were SMOTE-balanced and evaluated on held-out test sets using Accuracy, ROC-AUC, and F1-score, with 10,000-iteration bootstrap testing for statistical significance.

RESULTS: The stacked ensemble achieved the highest performance: ROC AUC = 0.70 (burnout), 0.93 (Long COVID), and 0.93 (extended leave). The F1 scores were >0.89 for Long COVID and extended leave, whereas the performance gains for burnout were comparatively modest, reflecting the multidimensional and heterogeneous nature of burnout as a binary construct. The gains over logistic regression were statistically significant (p < 0.0001 for Long COVID and extended leave; p = 0.0355 for burnout). The SHAP analysis identified overlapping top predictors-tenure, age, job role, cancer history, pulmonary disease, and obesity-supporting the value of a unified framework.

CONCLUSIONS: We trained separate models for each occupational health risk but deployed them in a single, real-time web application. This integrated approach improves efficiency, enables multi-outcome workforce surveillance, and supports proactive interventions in healthcare settings.},
}

@article {pmid41007828,
year = {2025},
author = {Dotor-Llerena, AL and Reyes-Long, S and Najera-García, L and Hernández-Corral, S and Arechaga-Ocampo, E and Avendaño-Ortiz, K and Trejo-Martínez, D and Rosell-Becerril, H and Cortes-Altamirano, JL and Alfaro-Rodríguez, A},
title = {The Effect of Neurorehabilitation of the Cognitive Symptoms of Long COVID Evaluated with Neuropsi Atención y Memoria-III and BANFE-III.},
journal = {Biomedicines},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/biomedicines13092267},
pmid = {41007828},
issn = {2227-9059},
abstract = {Background: The long-haul symptoms of COVID-19 have not been properly attended, especially those of the central nervous system. Attention, memory and executive functioning are the three main cognitive symptoms reported for long COVID patients. To this day, neurorehabilitation therapy to alleviate these symptoms has not been proposed. Objectives: The current study aims to evaluate the effect of a neurorehabilitation intervention on the three most prevalent symptoms reported for long COVID in Mexican patients: memory, attention and executive functioning. Methods: Subjects were recruited at Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra and underwent a novel neurorehabilitation intervention for 6 months. Baseline measurements were taken using validated instruments (Neuropsi, BANFE and CCQ) before the intervention and after it. Results: A significant decrease in the normalized score of the Memory component of the Neuropsi Atención y Memoria III test was found after the intervention, along with a decrease in two components of the BANFE-III test. Conclusions: In the current study, a successful neuropsychology intervention for the main cognitive symptoms of long COVID in a Mexican population reduced subjective self-perceived complaints and objectively measured cognitive symptoms.},
}

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

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

@article {pmid41007081,
year = {2025},
author = {Goicoechea-Calvo, A and Coll-Fernández, R and Navarro Expósito, N and Colomer Giralt, M and González-Aumatell, A and Méndez-Hernández, M and Carreras-Abad, C and Pallarès Fontanet, N and Tebe Cordomi, C and Durà Mata, MJ and Rodrigo, C},
title = {Effects of Paediatric Post-COVID-19 Condition on Physical Function and Daily Functioning: A Cross-Sectional Study.},
journal = {Children (Basel, Switzerland)},
volume = {12},
number = {9},
pages = {},
doi = {10.3390/children12091216},
pmid = {41007081},
issn = {2227-9067},
abstract = {BACKGROUND/OBJECTIVES: Lack of objective evidence exists regarding changes in physical function and impact on daily functioning in paediatric post-COVID-19 condition (PPCC). This study aimed to assess exercise capacity, fatigue, and peripheral and respiratory muscle strength in PPCC patients compared with healthy controls. Additionally, the impact of PPCC on domains of daily life was evaluated.

METHODS: A cross-sectional study was performed.

STUDY VARIABLES: exercise capacity (6 min walk test, 6MWT), inspiratory muscle strength (maximal inspiratory pressure, PImax), handgrip strength (handheld dynamometer, HHD), quadriceps femoris muscle thickness (QF MT), rectus femoris muscle thickness (RF MT), rectus femoris cross-sectional area (RF CSA), rectus femoris echo-intensity (RF EI), fatigue (Paediatric Functional Assessment of Chronic Illness Therapy-Fatigue, pedsFACIT-F), and physical activity (Assessment of Physical Activity Levels Questionnaire, APALQ).

RESULTS: A total of 115 PPCC patients and 227 healthy controls were included. The PPCC group had lower 6MWT (509.00 ± 86.12, p < 0.001), PImax (68.71 ± 26.23, p < 0.001), HHD (82.84 ± 29.09, p < 0.001), APALQ (7.94 ± 3.14, p < 0.001), pedsFACIT-F (24.51 ± 11.01, p < 0.001), QF MT mid-thigh (33.21 ± 7.99, p = 0.011), and higher RF EI (p < 0.001) vs. controls. Only 37.63% of the PPCC group resumed previous sports, 43.48% were unable to attend school full-time and 28.7% could not participate in after-school activities.

CONCLUSIONS: Paediatric post-COVID-19 condition patients exhibited significant impairments in terms of physical function, with a high impact on daily functioning. This knowledge is necessary to provide targeted therapeutic interventions.},
}

@article {pmid41004911,
year = {2025},
author = {Chen, TY and Chu, YJ and Hsu, CJ and Wang, HP and Wong, LC and Lee, WT},
title = {Long-Term Influence of Pediatric Long COVID Syndrome on Visual Perception and Neuropsychiatric Symptoms.},
journal = {Pediatric neurology},
volume = {173},
number = {},
pages = {22-29},
doi = {10.1016/j.pediatrneurol.2025.08.018},
pmid = {41004911},
issn = {1873-5150},
abstract = {BACKGROUND: Long COVID presents with a wide range of persistent symptoms and durations following coronavirus disease 2019 (COVID-19) infection. However, data on children and adolescents remain limited. This study aims to explore visual perception and neuropsychiatric symptoms in pediatric patients and examine their associations with brain volume differences.

METHODS: A total of 60 participants, aged six to 18 years and confirmed COVID-19 antibody positive, were recruited five to eight months after infection. Owing to the diversity of symptoms, each symptom was assigned a weighted score from 0 to 3 based on its severity and relevance to brain function. Participants were then divided into two groups according to symptom severity. All participants underwent magnetic resonance imaging, and the Test of Visual Perceptual Skills-Fourth Edition (TVPS-4) was administered.

RESULTS: The most common neuropsychiatric symptoms were headache or dizziness, along with attention and memory deficits, which persisted for up to six months. Gray matter volumes were significantly increased in the group with severe symptoms, particularly in subcortical and temporal regions. These brain volume differences showed significant correlations with both acute and chronic symptoms. In the TVPS-4 assessment, significant differences were observed in overall standard scores and in the Sequential Memory subtest between participants with visual-related symptoms and healthy control subjects.

CONCLUSIONS: Neuropsychiatric symptoms, impaired visual perception, and gray matter volume differences are evident in pediatric long COVID cases. The severity of neuropsychiatric symptoms during the acute phase may predict the degree of chronic-phase brain volume alterations. Longitudinal follow-up studies are essential to validate and expand upon these findings.},
}

@article {pmid41004337,
year = {2025},
author = {Calvache-Mateo, A and Rodríguez-López, A and Navas-Otero, A and Martín Núñez, J and Heredia-Ciuró, A and López-López, L and Valenza, MC},
title = {Impairment of neural mechanosensitivity in the Long COVID haulers.},
journal = {Expert review of respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1080/17476348.2025.2568243},
pmid = {41004337},
issn = {1747-6356},
abstract = {BACKGROUND: The aim of this study was to evaluate and characterize the alteration in mechanosensitivity in Long COVID haulers as well as its impact on patients' functionality and quality of life.

RESEARCH DESIGN AND METHODS: in this study there were two groups: a group of Long COVID haulers and a group of healthy controls matched for age and sex. The mechanosensitivity clinical profile and peripheral nerve mechanosensitivity were evaluated. The mechanosensitivity clinical profile included the functionality and quality of life (World Health Organization Disability Assessment Schedule 2.0, Patient-Reported Outcomes Measurement Information System, EuroQol-5 Dimensions) and neural mechanosensitivity (Leeds Assessment of Neuropathic Symptoms and Signs). The peripheral nerve mechanosensitivity included neurodynamic tests (median, radial, ulnar, slump test and straight leg raise).

RESULTS: A total of 64 patients were included in the study (Long COVID haulers group n = 33, healthy controls group n = 31). Long COVID haulers group obtained significantly worse results in functionality (p < 0.001), quality of life (p < 0.001), neural mechanosensitivity (p < 0.001) and peripheral nerve mechanosensitivity (p < 0.001).

CONCLUSIONS: Long COVID haulers have significant alterations in neural mechanosensitivity, contributing to a greater degree of functional impairment and poorer quality of life.},
}

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

@article {pmid41001233,
year = {2025},
author = {Torok, RA and Lubell, J and Rudy, RM and Eccles, J and Quadt, L},
title = {Variant connective tissue as a risk factor for long COVID: a case-control study of data from a retrospective online survey of adults in the USA and UK.},
journal = {BMJ public health},
volume = {3},
number = {2},
pages = {e002949},
pmid = {41001233},
issn = {2753-4294},
abstract = {INTRODUCTION: This study explored the extent to which two measures of joint hypermobility, a marker of variant connective tissue, predict the development of long COVID after COVID-19 infection, and whether the severity of initial COVID-19 symptoms impacts this relationship.

METHODS: We recruited 1816 participants (352 (19.4%) reporting long COVIDLong COVID, 1464 (80,6%) not reporting long COVIDLong COVID) from the US and UK for a retrospective online survey. The primary outcome was self-reported long COVIDLong COVID, defined as experiencing symptoms related to a COVID-19 infection at least 3 months after infection. Secondary outcomes included severity of symptoms during each COVID-19 infection, generalised joint hypermobility (GJH), and the novel concept of 'extreme hypermobility'.

RESULTS: In separate binomial logistic regressions controlling for sex assigned at birth, age, number of infections and number of vaccine doses, both GJH (OR 1.29, 95% CI 1.00 to 1.65) and extreme hypermobility (OR 2.12, 95% CI 1.43 to 3.16) were found to be predictive of long COVIDLong COVID. This likely occurs through two pathways. First, both GJH and extreme hypermobility increase the risk that individuals with no or moderate initial symptoms from a COVID-19 infection experience long COVIDLong COVID. Second, both GJH and extreme hypermobility are significant predictors of developing severe initial symptoms from a COVID-19 infection, which is independently associated with increased long COVID risk. A mediation analysis confirmed that extreme hypermobility influences the odds of developing long COVID in part by increasing the likelihood that individuals experience severe initial symptoms from a COVID infection.

CONCLUSIONS: Both GJH and extreme hypermobility are significant risk factors for long COVID. People with extreme hypermobility, as newly defined in this study, are at particularly high risk of developing long COVID after an initial COVID-19 infection. Further research is needed to replicate these findings with other datasets, clarify the pathophysiology that explains why people with hypermobility may be at greater risk of long COVID and assess the clinical significance of 'extreme hypermobility'.},
}

@article {pmid41000346,
year = {2025},
author = {Saito, A and Otake, S and Ohgino, K and Bun, S and Mimura, Y and Ito, D and Miyazaki, N and Nagashima, K and Terai, H and Chubachi, S and Masaki, K and Miyata, J and Kawada, I and Namkoong, H and Hashiguchi, M and Kagyo, J and Shiomi, T and Masuzawa, K and Asakura, T and Nakayama, S and Suzuki, Y and Minematsu, N and Manabe, T and Fukui, T and Funatsu, Y and Koh, H and Fukunaga, K},
title = {Anxiety, depression, and fear after coronavirus disease 2019 infection and their association with long coronavirus disease symptoms.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1672447},
pmid = {41000346},
issn = {1664-0640},
abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had widespread physical and psychological repercussions. Additionally, long COVID symptoms such as fatigue, dyspnea, and cognitive impairment have been well-documented; however, their associations with mental health symptoms remain unclear. This study investigated the relationships between long COVID and symptoms of anxiety, depression, and COVID-19-related fear using validated psychological assessment tools.

METHODS: This nationwide, prospective cohort study enrolled 1,066 individuals who recovered from COVID-19. The participants completed self-report questionnaires at 3, 6, and 12 months after diagnosis. Long COVID symptoms and psychological status were assessed using the Hospital Anxiety and Depression Scale (HADS) and Fear of COVID-19 Scale (FCV-19S). Statistical analyses were used to examine associations between long COVID symptoms and psychological scores while accounting for clinicodemographic factors.

RESULTS: Three months after diagnosis, 20.1% of the participants exhibited high anxiety (HADS-Anxiety [A] score ≥ 8), 23.6% had high depression (HADS-Depression [D] score ≥ 8), and 35.3% reported high levels of COVID-19-related fear (FCV-19S score ≥ 21). High HADS-A and HADS-D scores were significantly associated with younger age, female sex, and mild initial illness severity. Individuals with high HADS scores reported significantly greater long COVID symptoms; headaches and fatigue were associated with high anxiety scores and impaired concentration was associated with high depression scores.

CONCLUSIONS: This study highlighted the significant associations between mental health symptoms and long COVID, emphasizing the need for integrated psychological support in post-COVID care. Addressing anxiety, depression, and fear-related concerns may contribute to improved management of long COVID symptoms and enhance overall patient well-being.},
}

@article {pmid40880119,
year = {2025},
author = {Bobato, GR and Rocha, JQ and Guizoni, DM and Nóbrega, NRC and Moura, LD and Rocha, ML and Velloso, LA and Carneiro, EM and Antunes-Correa, LM and Davel, AP},
title = {Extracellular vesicles from post-COVID-19 patients alter endothelial function under protein restriction.},
journal = {American journal of physiology. Cell physiology},
volume = {329},
number = {4},
pages = {C1121-C1129},
doi = {10.1152/ajpcell.00450.2025},
pmid = {40880119},
issn = {1522-1563},
mesh = {*COVID-19/metabolism/complications/physiopathology/pathology ; *Extracellular Vesicles/metabolism/pathology ; Animals ; Humans ; Male ; *Endothelium, Vascular/metabolism/physiopathology ; Mice ; Female ; *Diet, Protein-Restricted/adverse effects ; Vasodilation/drug effects ; *Endothelial Cells/metabolism ; Middle Aged ; Mice, Inbred C57BL ; Aged ; Aorta/metabolism ; SARS-CoV-2 ; },
abstract = {The COVID-19 pandemic worsened global food insecurity and malnutrition. Protein restriction increases the risk of poor COVID-19 outcomes and cardiovascular disease. Post-COVID-19 syndrome remains a public health concern, although its underlying mechanisms are not yet fully understood. Extracellular vesicles (EVs), released by most cell types in response to infections, have been implicated in endothelial dysfunction during the post-COVID phase. We hypothesized that EV contribute to endothelial cell (EC) dysfunction in long-term COVID-19, particularly in the setting of protein malnutrition. Circulating EVs were isolated from patients at 1 and 6 months (mo) after hospital discharge due to severe COVID-19. Endothelial relaxation was assessed in mouse aortas after a 3-mo normoprotein or low-protein diet (LP). LP feeding reduced endothelium-dependent relaxation to acetylcholine, but EVs from post-COVID patients (1 and 6 mo) restored endothelium-dependent relaxation. This EV effect was abolished by catalase, but not by l-NAME (a nitric oxide synthase inhibitor) or indomethacin (a cyclooxygenase inhibitor). Aortas from LP mice incubated with post-COVID EVs exhibited reduced catalase expression and increased 4-hydroxynonenal (4-HNE) adducts. In vitro amino acid restriction increased EC death (Hoechst/Pi), and reduced nitric oxide (Diaminofluorescein-FM diacetato) and H2O2 (Amplex red) levels. Incubation with post-COVID EVs for 24 h increased H2O2 only in amino acid-restricted EC. EVs had no significant effect on acetylcholine-induced relaxation in normoprotein-fed mice or on EC parameters in vitro under control conditions. These findings suggest that EVs from patients 1 and 6 mo after severe COVID-19 impact aortic endothelial function by increasing H2O2 contribution under conditions of malnutrition.NEW & NOTEWORTHY Our study demonstrated that circulating extracellular vesicles (EVs) from patients 1 and 6 mo after severe COVID-19 altered endothelial function under protein restriction but not in healthy vessels. Post-COVID EVs enhanced the contribution of H2O2 to endothelium-dependent relaxation, associated with reduced catalase and increased 4-HNE-modified protein expression. These findings identified EVs from long COVID patients as potential mediators of endothelial dysfunction particularly under malnutrition-related conditions.},
}

*COVID-19/metabolism/complications/physiopathology/pathology
*Extracellular Vesicles/metabolism/pathology
Animals
Humans
Male
*Endothelium, Vascular/metabolism/physiopathology
Mice
Female
*Diet, Protein-Restricted/adverse effects
Vasodilation/drug effects
*Endothelial Cells/metabolism
Middle Aged
Mice, Inbred C57BL
Aged
Aorta/metabolism
SARS-CoV-2

@article {pmid40996864,
year = {2025},
author = {Hemming, PE and Arvizu, LS and Yadon, CA},
title = {Sensory and cognitive experiences after COVID-19 infection in college students.},
journal = {Journal of American college health : J of ACH},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/07448481.2025.2561890},
pmid = {40996864},
issn = {1940-3208},
abstract = {OBJECTIVE: This project examined sensory and cognitive processing after COVID-19 infection in college students.

PARTICIPANTS: The final sample included 424 undergraduate students (M age = 19.36).

METHODS: A survey was administered to gather demographics, infection history, and sensory and cognitive experiences following COVID-19, including stress, experiential measures of sensory gating and processing, cognition, sleep, olfactory function, and emotional implications.

RESULTS: Greater perceived COVID-19 severity was significantly associated with poorer sleep quality, sensory processing difficulties, and more cognitive failures. Similarly, participants with lingering symptoms reported significantly poorer sensory, sleep, and cognitive experiences. More difficulty filtering sensory input and poorer sleep predicted higher reported COVID-19 severity. Among those currently experiencing brain fog, greater perceived impact of this symptom was moderately associated with more cognitive failures. Descriptive statistics for emotional implications are provided.

CONCLUSIONS: Lingering COVID-19 symptoms and perceived severity may be associated with sensory and cognitive challenges in college students.},
}

@article {pmid40996671,
year = {2025},
author = {Gao, Z and Tabernacki, T and Davis, PB and Kaelber, DC and Xu, R},
title = {Associations of selective serotonin reuptake inhibitors and long COVID risk in patients with depression: a retrospective cohort study.},
journal = {Infection},
volume = {},
number = {},
pages = {},
pmid = {40996671},
issn = {1439-0973},
support = {AG07664, AG057557, AG061388, and AG062272/AG/NIA NIH HHS/United States ; AA029831/AA/NIAAA NIH HHS/United States ; },
abstract = {PURPOSE: To evaluate the potential of selective serotonin reuptake inhibitors (SSRIs) in reducing the risk of long COVID in patients with depression.

METHODS: This retrospective cohort study analyzed U.S. electronic health records from TriNetX platform to compare the risk of long COVID among adults with depression who were prescribed SSRIs versus non-SSRI antidepressants between March 2020 and December 2022. The main outcome was the long COVID diagnosis. As a sensitivity analysis, CDC-defined long COVID symptoms were used as alternative outcomes. Cox proportional hazards models were used to assess outcomes occurring 3-6 and 3-12 months after the index SARS-CoV-2 infection, with hazard ratios (HRs) and 95% confidence intervals (CIs) calculated.

RESULTS: After propensity score matching, the study included 31,264 patients, and the risk of long COVID diagnosis was significantly lower in the SSRI cohort compared to the matched non-SSRI antidepressant cohort, with hazard ratios of 0.57 (95% CI: 0.44-0.73) for the 3-6-month period and 0.59 (95% CI: 0.49-0.72) for the 3-12-month period. Sensitivity analyses in matched cohorts of 17,100 patients showed that SSRI use was associated with a significantly reduced risk of long COVID symptoms, consistent across symptom categories and pandemic periods.

CONCLUSIONS: In adult patients with depression, SSRIs compared with non-SSRI antidepressants were associated with a lower risk of long COVID. These results offer preliminary evidence that SSRIs may help prevent long COVID in high‑risk populations and warrant further preclinical and clinical investigation.},
}

@article {pmid40996592,
year = {2025},
author = {Zhao, J and Lyu, Y and Qu, J},
title = {Insights into potential therapeutic approaches for long COVID.},
journal = {Frontiers of medicine},
volume = {},
number = {},
pages = {},
pmid = {40996592},
issn = {2095-0225},
}

@article {pmid40996585,
year = {2025},
author = {Prociuk, D and Clarke, J and Smith, N and Milne, R and Lee, C and de Lusignan, S and Mir, G and De Kock, J and Mayer, E and Delaney, BC and , },
title = {Understanding the Clinical Characteristics and Timeliness of Diagnosis for Patients Diagnosed With Long Covid: A Retrospective Observational Cohort Study From North West London.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70429},
pmid = {40996585},
issn = {1369-7625},
support = {//This study was funded by the National Institute for Health and Care Research Ref: COV-LT2-0016. Infrastructure support for this study was provided by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (NIHR203323), the NIHR North-West London Patient Safety Research Collaboration (NIHR NWL PSRC, Ref. NIHR204292) and the NIHR Oxford Biomedical Research Centre. J.C. acknowledges funding from the Wellcome Trust (215938/Z/19/Z)./ ; },
mesh = {Humans ; London/epidemiology ; Retrospective Studies ; Female ; Male ; *COVID-19/diagnosis/epidemiology/complications ; Middle Aged ; Adult ; Aged ; Primary Health Care ; Time Factors ; SARS-CoV-2 ; Incidence ; },
abstract = {BACKGROUND: Long Covid is a multisystem condition first identified in the Covid-19 pandemic, characterised by a wide range of symptoms including fatigue, breathlessness and cognitive impairment. Considerable disagreement exists in who is most at risk of developing long Covid, driven in part by incomplete coding of a long Covid diagnosis in medical records.

OBJECTIVE: To describe the incidence and impact of long Covid.

DESIGN: A retrospective observational cohort study.

SETTING AND PARTICIPANTS: An integrated primary and secondary care dataset from North West London, covering over 2.7 million patients. Patients with long Covid were identified through clinical terms in their primary care records.

MAIN VARIABLES STUDIED: Multivariate logistic regression was used to identify factors associated with having a long Covid diagnosis, while multivariate quantile regression was used to identify factors predicting the time a long Covid diagnosis was recorded.

RESULTS: A total of 6078 patients were identified with a long Covid clinical term in their primary care record, 0.33% of the total registered adult population. Women, those aged 41-70 years or of Asian or mixed ethnicity, were more likely to have a recorded long Covid diagnosis, alongside those with pre-existing anxiety, asthma, depressive disorder or eczema and those living outside of the least or most socio-economically deprived areas. Men, those aged 41-70 years, or of black ethnicity, were diagnosed earlier in the pandemic, while those with depressive disorder were diagnosed later.

DISCUSSION: Long Covid is poorly coded in primary care records, and significant differences exist between patient groups in the likelihood of receiving a long Covid diagnosis. A recorded long Covid diagnosis is more likely in women, some ethnic minority patients and those with pre-existing long-term conditions.

CONCLUSION: The experience of patients with long Covid provides a crucial insight into inequities in access to timely care for complex multisystem conditions and the importance of effective health informatics practices to provide robust, timely analytical support for front line clinical services.

This study was co-designed, conducted and written in conjunction with people with long Covid.},
}

Humans
London/epidemiology
Retrospective Studies
Female
Male
*COVID-19/diagnosis/epidemiology/complications
Middle Aged
Adult
Aged
Primary Health Care
Time Factors
SARS-CoV-2
Incidence

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

@article {pmid40995223,
year = {2025},
author = {Botelho, MC and Poma, AM and Wu, J},
title = {Editorial: Extrapulmonary manifestations of SARS-CoV-2 infection and COVID-19 vaccine adverse effects.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1688071},
doi = {10.3389/fcimb.2025.1688071},
pmid = {40995223},
issn = {2235-2988},
}

@article {pmid40995163,
year = {2025},
author = {Amedee, RG},
title = {Focusing on Long COVID and HIV Prevention.},
journal = {Ochsner journal},
volume = {25},
number = {3},
pages = {151},
doi = {10.31486/toj.25.5056},
pmid = {40995163},
issn = {1524-5012},
}

@article {pmid40995151,
year = {2025},
author = {Thomas, LDL},
title = {When We Don't Have All the Answers: Long COVID and the Need for Humility in Medicine.},
journal = {Ochsner journal},
volume = {25},
number = {3},
pages = {152-158},
pmid = {40995151},
issn = {1524-5012},
}

@article {pmid40991647,
year = {2025},
author = {Becker, JH and Watson, E and Zubair, N and Carnavali, F and Bagiella, E and Reich, D and Wisnivesky, JP},
title = {Preliminary evaluation of a cognitive rehabilitation intervention for post-COVID-19 cognitive impairment: A pilot randomized controlled trial.},
journal = {Neuropsychological rehabilitation},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/09602011.2025.2552154},
pmid = {40991647},
issn = {1464-0694},
abstract = {BACKGROUND: Despite the profound impact of "brain fog" and/or cognitive impairment in relatively young people with Long COVID, no interventions with demonstrated efficacy are currently available. We conducted a pilot randomized controlled trial investigating the preliminary outcomes of a cognitive rehabilitation (CR) intervention adapted for persons with post-COVID cognitive impairment.

METHODS: Participants were ≥18 years of age, English-speaking, had history of SARS-CoV-2, and had cognitive impairment on objective measures. Eligible participants were randomized to a 12-week CR intervention or a time - and attention-matched control arm. Objective and subjective cognitive functioning was assessed at pre - and within 2-weeks post-intervention, utilizing validated neuropsychological measures across multiple domains. We compared pre vs. post intervention changes in cognitive scores in intervention vs. control groups.

RESULTS: The mean change in the intervention group compared to the controls in measures of processing speed, learning, memory, language, and of executive function did not reach the threshold for futility. In comparison to controls, the intervention group self-reported significant improvements in cognitive functioning.

CONCLUSIONS: We found that an adapted CR intervention for Long COVID may improve post-COVID cognitive impairment in comparison to a time - and attention-matched control group and should be evaluated in a larger trial.

UNLABELLED: Trial registration: ClinicalTrials.gov identifier: NCT05498493. Registered on 08/10/2022.},
}

@article {pmid40991619,
year = {2025},
author = {Almeida, IDS and Ferreira, LGJ and Vaz, MA and Cipriano Junior, G and de Resende, MA and Vieira, DCL and Costa, RR and Babault, N and Marqueti, RC and Durigan, JLQ},
title = {Fatigue and neuromuscular function in long COVID: A one-year follow-up study.},
journal = {PloS one},
volume = {20},
number = {9},
pages = {e0332242},
doi = {10.1371/journal.pone.0332242},
pmid = {40991619},
issn = {1932-6203},
mesh = {Humans ; Male ; *COVID-19/complications/physiopathology ; Female ; Middle Aged ; Adult ; Follow-Up Studies ; *Fatigue/physiopathology/etiology ; Longitudinal Studies ; SARS-CoV-2 ; Muscle Fatigue ; Muscle, Skeletal/physiopathology ; Brazil ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long COVID has emerged as a significant complication of SARS-CoV-2 infection. However, the long-term neuromuscular consequences of this condition, particularly one-year post-infection, remain poorly understood. This study aimed to determine the mechanisms of fatigue by comparing perceived fatigue, objective fatigability, functionality, muscle architecture, and electrical neuromuscular function in participants who had suffered severe or moderate COVID‑19 one-year post-infection with a healthy control group.

METHODS AND FINDINGS: This longitudinal observational study followed participants for one-year. The assessments were conducted at the Laboratory of Muscle and Tendon Plasticity at the University of Brasília, Brazil. Participants who had suffered moderate or severe SARS-CoV-2 infection were compared to a control group. A baseline assessment was initially conducted (21-30 days post-symptoms onset or post-hospital discharge), followed by second (31-90), third (91-180), and fourth (181-360) assessments. Perceived fatigue, objective fatigability, functionality, muscle architecture, and electrical neuromuscular function were analyzed. The study included 30 controls (46.53 [42.10-51.43] years; 13 men [43.33%]), 22 moderate cases (38.27 [33.96-43.13] years; 10 men [45.45%]), and 18 severe cases (50.83 [45.19-57.18] years; eight men [44.44%]). Severe participants exhibited higher perceived fatigue in all assessments than the control group and at baseline and in assessment 4 compared to moderate cases, in addition to a lower torque and torque-time integral in all assessments of objective fatigability analysis compared to the other groups. The severe group also demonstrated reduced functionality, impaired muscle architecture (characterized by increased echogenicity), and higher chronaxie values in the electrical neuromuscular function assessment. Participants with moderate COVID‑19 exhibited alterations in perceived fatigue, reduced torque, and lower TTI, electrical neuromuscular function, and muscle architecture, particularly at baseline.

CONCLUSIONS: Severe participants continued to experience significant perceived fatigue even one-year post-infection, suggesting a slower recovery trajectory, that contributed to increased fatigability throughout the follow-up period. These results emphasize the role of musculoskeletal and neural mechanisms in post-COVID‑19 fatigue, highlighting the need for targeted, mechanism-based rehabilitation strategies.

TRIAL REGISTRATION: NCT04961255.},
}

Humans
Male
*COVID-19/complications/physiopathology
Female
Middle Aged
Adult
Follow-Up Studies
*Fatigue/physiopathology/etiology
Longitudinal Studies
SARS-CoV-2
Muscle Fatigue
Muscle, Skeletal/physiopathology
Brazil
Post-Acute COVID-19 Syndrome

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

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

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

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

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

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

@article {pmid40987251,
year = {2025},
author = {Zhang, Y and Jiang, C and Jiang, W and Yuan, Y and Cao, D and Yuan, Y},
title = {Development and clinimetric validation of the Brief Brain Fog Scale (BBFS) for post-COVID cognitive symptoms.},
journal = {Journal of psychosomatic research},
volume = {198},
number = {},
pages = {112380},
doi = {10.1016/j.jpsychores.2025.112380},
pmid = {40987251},
issn = {1879-1360},
abstract = {OBJECTIVES: To develop and clinimetrically validate the Brief Brain Fog Scale (BBFS), a concise self-report tool for assessing post-COVID-19 cognitive symptoms, and to evaluate its structural validity, reliability and precision.

METHODS: The BBFS was generated from literature and expert review and finalized as five items targeting core brain-fog symptoms.A total of 844 participants completed an online cross-sectional survey, including 686 with self-reported post-COVID brain fog and 158 healthy controls. Rasch modeling and Mokken scaling were used to examine unidimensionality, item fit, person reliability, and item scalability. Local independence and differential item functioning (DIF) were assessed across age, sex, and education groups.

RESULTS: The BBFS fit Rasch model expectations (χ[2] = 44.6, df = 60, p = 0.928) and showed strong scalability (Mokken H = 0.679). Reliability was high (PSI = 0.846; WLE reliability = 0.846; EAP reliability = 0.852), with optimal precision in the moderate symptom range. All items had acceptable Infit MNSQ values (0.5-1.5), though several exhibited elevated Outfit in the highest response category. Local independence was largely supported; one pair marginally exceeded the indicative Q3[⁎] threshold (0.204), and none exceeded 0.30. Uniform DIF was identified across age, sex, and education. Two items showed lower thresholds in older respondents, two showed higher thresholds in females, and four showed lower thresholds in postgraduate respondents. 'Forgetful' did not exhibit education-related DIF.

CONCLUSIONS: The BBFS is a reliable, unidimensional instrument for post-COVID brain fog, with robust measurement properties supported by Rasch and Mokken analyses. Although some items showed demographic sensitivity, the total scale functioned consistently across groups. The BBFS represents a potentially valid and practical screening instrument. Future work should examine longitudinal responsiveness, cross-cultural generalizability, and item refinements.},
}

@article {pmid40986436,
year = {2025},
author = {Santos, GA and Laranjeira, C and Carreira, L and Baldissera, VDA and Tostes, MFDP and Meireles, VC and Ageno, RS and Salci, MA},
title = {Living With Persistent Respiratory Symptoms of Long COVID: Qualitative Study Among Brazilian Adults 12 Months After Acute Infection.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {28},
number = {5},
pages = {e70409},
doi = {10.1111/hex.70409},
pmid = {40986436},
issn = {1369-7625},
support = {//This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-Processo no. 402,882/2020-2. 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 25 July 2025]./ ; },
mesh = {Humans ; Brazil/epidemiology ; Female ; *COVID-19/complications/psychology/physiopathology ; Male ; Adult ; Qualitative Research ; Middle Aged ; SARS-CoV-2 ; Grounded Theory ; Post-Acute COVID-19 Syndrome ; Interviews as Topic ; Dyspnea/etiology ; },
abstract = {INTRODUCTION: The majority of those infected with COVID-19 undergo a brief duration of clinical illness. In certain instances, symptoms endure for months or years after the initial viral exposure-a condition characterized as Long COVID (LC). The experience of this illness remains largely unexplored as it has only recently surfaced. This study aims to understand the repercussions of persistent respiratory post-COVID symptoms in Brazilian adults 12 months after SARS-CoV-2 infection.

METHODS: A constructivist grounded theory study was employed. Data were collected through individual interviews with adults with persistent respiratory symptoms of Long COVID in Brazil. Data collection took place between September 2023 and February 2024. Data analysis was performed on a constant comparative basis and concurrent with data collection to understand the findings.

RESULTS: Twenty-four individuals (12 females, 12 males) with a median age of 43.29 ± 9.09 years participated. The data analysis generated a central category-living with the long-term effects of COVID-19: breathlessness pervades everything-around which three categories emerged: (1) imbalance between life before and after being infected by COVID-19; (2) living with acute post-COVID respiratory symptoms; and (3) struggling with persistent post-COVID respiratory symptoms.

CONCLUSION: Our analysis of the perceived needs of individuals with Long COVID underscores the urgent necessity for legislative reform to acknowledge LC as a disability that requires clear diagnostic criteria. Approaches to treatment and rehabilitation are required to evaluate the extent to which functioning and disability improve. Lastly, this study highlights the complex problems encountered by individuals with Long COVID, including employment uncertainties, everyday tasks and social relationships.},
}

Humans
Brazil/epidemiology
Female
*COVID-19/complications/psychology/physiopathology
Male
Adult
Qualitative Research
Middle Aged
SARS-CoV-2
Grounded Theory
Post-Acute COVID-19 Syndrome
Interviews as Topic
Dyspnea/etiology

@article {pmid40985761,
year = {2025},
author = {Hang Lam, IC and Zhou, J and Liu, W and Cheung Man, KK and Zhang, Q and Luo, H and Ho Wong, CK and Ling Chui, CS and Tsun Lai, FT and Li, X and Yin Chan, EW and Kei Wong, IC and Fai Wan, EY},
title = {Development and validation of age-specific predictive model on the risk of post-acute mortality within one year of COVID-19 infection.},
journal = {QJM : monthly journal of the Association of Physicians},
volume = {},
number = {},
pages = {},
doi = {10.1093/qjmed/hcaf218},
pmid = {40985761},
issn = {1460-2393},
abstract = {BACKGROUND: The existing risk prediction models for COVID-19 associated mortality have not considered the difference in risk factors in patients across an aging population.

AIM: To develop age-specific prediction models to forecast the risk of all-cause mortality in patients recovering from COVID-19 infection.

DESIGN: Population-based, retrospective cohort study.

METHODS: Patients with COVID-19 between 1 April 2020 and 31 July 2022 survived beyond the acute phase of infection were stratified into separate age cohorts (<45, 45-64, ≥65) and followed-up for one year. Backward stepwise logistic regression and four statistical and machine learning algorithms were employed to develop age-specific models on the risk of post-acute mortality following COVID-19 infection, based on a comprehensive set of clinical parameters including demographics, COVID-19 vaccination status, pre-existing comorbidities and laboratory-test findings.

RESULTS: Of the 891,246 patients with COVID-19 identified, 13,578 (1.05%) died within one year of the index date. Age, COVID-19 vaccination status and history of acute respiratory syndrome prior infection were identified as predictors in the models for separate age groups. The model for patients aged ≥65 exhibited excellent prediction performance with an AUROC of 0.87 (95% CI: 0.87, 0.88), followed by the model for patients aged 45-64 [AUROC=0.83 (95% CI: 0.81, 0.85)] and those aged <45 [AUROC=0.79 (95% CI: 0.72, 0.86)].

CONCLUSION: The age-specific models reported accurately predicted the risk of post-acute mortality in their corresponding age-group of patients, providing valuable asset in optimising clinical strategies and resource allocation in the management of the global burden of Long COVID.},
}

@article {pmid40984162,
year = {2025},
author = {Flattum-Riemers, T and Susi, A and Nylund, C},
title = {Incidence Trends and Co-Diagnosis of Post-COVID-19 Condition in the Active Duty Population.},
journal = {Military medicine},
volume = {190},
number = {Supplement_2},
pages = {599-604},
doi = {10.1093/milmed/usaf283},
pmid = {40984162},
issn = {1930-613X},
support = {//intramural Uniformed Services University of Health Sciences/ ; //Department of Defense High Priority Award/ ; },
mesh = {Humans ; Incidence ; *COVID-19/epidemiology/complications ; *Military Personnel/statistics & numerical data ; Female ; Male ; Adult ; Cross-Sectional Studies ; Middle Aged ; United States/epidemiology ; Adolescent ; },
abstract = {INTRODUCTION: Long COVID, also known as Post-COVID-19 Condition (PCC) is characterized by the persistence or development of symptoms following SARS-CoV-2 infection. Post-COVID-19 Condition has the potential to impact military readiness, and yet the incidence among active duty service members (ADSM) is unknown. The objective of this study is to assess the incidence of diagnosed PCC, explore demographic associations, and identify common co-occurring diagnoses among ADSM.

MATERIALS AND METHODS: We conducted a repeated cross-sectional study using the Military Health System Data Repository (MDR). The MDR was queried for care records containing the ICD-10 code for PCC, U09.9, from October 2021 to October 2022. Incidence was calculated using the monthly counts, although Incidence Rate Ratios were calculated using a Poisson regression model, adjusting for age, sex, rank, race/ethnicity, and region. The frequency of co-occurring diagnoses with PCC encounters was analyzed to identify the top co-occurring diagnoses.

RESULTS: A total of 7,171 ADSM were diagnosed with PCC. The average monthly incidence of PCC was 4.7 per 10,000 ADSM. Females had 3.70 times (95% CI, 3.50-3.90) the adjusted incident rate ratio (aIRR) of PCC compared to males. Active duty service members aged 55-64 had the greatest risk with an aIRR of 28.81 (95% CI, 20.81-38.75) compared to ADSM aged 17-24. The highest frequency co-occurring diagnoses were respiratory signs and symptoms, with 874 diagnosed with R06.02 (shortness of breath).

CONCLUSION: Post-COVID-19 Condition represents a significant burden on the health of ADSM. Further research is warranted to study trends of PCC among the ADSM and to assess the effect of PCC on readiness and retention.},
}

Humans
Incidence
*COVID-19/epidemiology/complications
*Military Personnel/statistics & numerical data
Female
Male
Adult
Cross-Sectional Studies
Middle Aged
United States/epidemiology
Adolescent

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

@article {pmid40981197,
year = {2025},
author = {Matangkha, K and Punyahotara, V and Rintra, J and Sittiprapaporn, P},
title = {Association Between Vitamin D Levels and Long COVID Signs and Symptoms.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {3},
pages = {},
doi = {10.3390/medsci13030199},
pmid = {40981197},
issn = {2076-3271},
mesh = {Humans ; *COVID-19/blood/epidemiology/complications ; Female ; Male ; Adult ; *Vitamin D/blood/analogs & derivatives ; Middle Aged ; SARS-CoV-2 ; Young Adult ; *Vitamin D Deficiency/blood/epidemiology ; Adolescent ; Prevalence ; },
abstract = {BACKGROUND: "Long COVID" refers to a condition in which individuals continue to experience persistent signs and symptoms even after recovering from the initial COVID-19 infection. Signs and symptoms that persist can affect multiple organs in the body. Vitamin D is an essential nutrient that plays a crucial role, particularly in the immune system, and may be linked to the development of long COVID.

OBJECTIVE: The study aimed to investigate the association between vitamin D levels and the prevalence of long COVID signs and symptoms in COVID-19 patients.

MATERIALS AND METHODS: The study enrolled 170 COVID-19 patients with mild signs and symptoms and confirmed COVID-Ag or RT-PCR tests. The subjects were aged 18-59 years. All patients had 25(OH)D levels measured within 60 days of COVID-19 diagnosis and had been followed for at least 3 months post-infection. Data collected included demographic characteristics, serum 25(OH)D levels, and self-reported long COVID signs and symptoms questionnaire responses.

RESULTS: The study results indicated a female-to-male ratio of 1.1:1 and a mean age of 45.87 ± 8.65 years; of these, 62.4% received three doses of the COVID-19 vaccine, and 64.7% developed long COVID. The most prevalent signs and symptoms were respiratory (55.3%), skin (50.6%), and general (39.4%). The median blood vitamin D level was 22.96 ng/mL, with 41.2% of subjects having insufficient levels, 30.6% having deficient levels, and 28.2% having sufficient levels. Patients with long COVID had significantly lower vitamin D levels compared with those without long COVID (21.52 ng/mL vs. 25.46 ng/mL; p < 0.05). Multivariable analysis found that vitamin D deficiency was significantly associated with overall long COVID signs and symptoms (Adj. OR, 5.80 [95% CI: 2.10, 16.13]). Additionally, vitamin D deficiency significantly increased the number of long COVID systemic signs and symptoms (Adj. IRR, 3.30 [2.12, 5.12]).

CONCLUSION: Assessing and maintaining vitamin D levels, vitamin D supplementation, and sunlight exposure in COVID-19 patients can reduce the risk and severity of long-term COVID-19 signs and symptoms.},
}

Humans
*COVID-19/blood/epidemiology/complications
Female
Male
Adult
*Vitamin D/blood/analogs & derivatives
Middle Aged
SARS-CoV-2
Young Adult
*Vitamin D Deficiency/blood/epidemiology
Adolescent
Prevalence

@article {pmid40980765,
year = {2025},
author = {Xiong, R},
title = {Advancing Digital Precision Medicine for Chronic Fatigue Syndrome through Longitudinal Large-Scale Multi-Modal Biological Omics Modeling with Machine Learning and Artificial Intelligence.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {40980765},
issn = {2331-8422},
abstract = {We studied a generalized question: chronic diseases like ME/CFS and long COVID exhibit high heterogeneity with multifactorial etiology and progression, complicating diagnosis and treatment. To address this, we developed BioMapAI, an explainable Deep Learning framework using the richest longitudinal multi-omics dataset for ME/CFS to date. This dataset includes gut metagenomics, plasma metabolome, immune profiling, blood labs, and clinical symptoms. By connecting multi-omics to a symptom matrix, BioMapAI identified both disease- and symptom-specific biomarkers, reconstructed symptoms, and achieved state-of-the-art precision in disease classification. We also created the first connectivity map of these omics in both healthy and disease states and revealed how microbiome-immune-metabolome crosstalk shifted from healthy to ME/CFS.},
}

@article {pmid40980657,
year = {2025},
author = {Ribeiro, HS and Frediani, MM and Marçal, L and Antonângelo, L and Catharina, GS and Yu, L and Zanetta, DMT and Mauad, T and Moreira, TCL and Gouveia, N and Busatto, GF and Carvalho, CRR and Burdmann, EA and , },
title = {Community-Acquired Acute Kidney Injury and Late Kidney Dysfunction in Survivors of COVID-19 Hospitalization.},
journal = {Kidney international reports},
volume = {10},
number = {9},
pages = {3032-3043},
pmid = {40980657},
issn = {2468-0249},
abstract = {INTRODUCTION: Data on the incidence and risk factors for renal long COVID are scarce. We aimed to investigate 2 acute kidney injury (AKI) phenotypes, namely community-acquired (CA; CA-AKI) and hospital-acquired (HA; HA-AKI), and the development of late kidney dysfunction in survivors of COVID-19 hospitalization.

METHODS: This is a prospective cohort study of survivors of moderate-to-severe COVID-19 hospitalization in Brazil, from March to August 2020. The patients were assessed for up to 11 months after hospital discharge. Exposure was CA-AKI and HA-AKI. The main outcome was kidney dysfunction defined as incident low estimated glomerular filtration rate (eGFR; < 60 ml/min per 1.73 m[2]) and/or eGFR decline ≥ 25% from discharge at follow-up. An adjusted binary logistic regression analysis was run.

RESULTS: A total of 655 survivors were evaluated (6.5 ± 1.9 follow-up months); 79% had AKI (35% CA and 43% HA); 14% used kidney replacement therapy (KRT). Late kidney dysfunction occurred in 28% of the patients (16% with incident low eGFR and 27% with eGFR decline ≥ 25%). CA-AKI, but not HA-AKI, was independently associated with late kidney dysfunction (adjusted odds ratio [aOR] = 7.3, 95% confidence interval (CI): 3.6-15.8 and aOR = 2.2, 95% CI: 0.9-4.8, respectively).

CONCLUSION: In conclusion, late kidney dysfunction affected 1 in 4 COVID-19 survivors. CA-AKI, but not HA-AKI, was an independent risk factor for late kidney dysfunction. These findings suggest that renal long COVID might be frequent and that a specific AKI phenotype (CA-AKI) may play a crucial role in its development. Our research highlights the need for CA-AKI prevention and for the long-term follow-up and care of patients affected by this AKI phenotype during COVID-19 infection.},
}

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

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

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

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

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

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

@article {pmid40979552,
year = {2025},
author = {Adebisi, YA and Alhur, AA and Alshahrani, NZ and Cañezo, VC and Cue, EG and Lucero-Prisno, DE},
title = {Pre-pandemic diabetes and risk of long COVID: longitudinal evidence.},
journal = {Journal of diabetes and metabolic disorders},
volume = {24},
number = {2},
pages = {207},
pmid = {40979552},
issn = {2251-6581},
abstract = {OBJECTIVE: To examine whether pre-pandemic diabetes is associated with an increased risk of Long COVID in a nationally representative UK cohort.

METHODS: We conducted a prospective cohort analysis using data from the UK Household Longitudinal Study. A total of 11,669 adults aged ≥ 16 years were followed from Wave 10 (2018-19) to Wave 14 (2022-23). The primary exposure, pre-pandemic diabetes, was defined at baseline (Wave 10) based on self-report of a doctor diagnosis. The primary outcome, Long COVID, was assessed at follow-up (Wave 14) and defined as self-reported symptoms lasting more than 12 weeks after a COVID-19 infection that could not be explained by another cause. Modified Poisson regression models with robust standard errors were used to estimate relative risks of Long COVID associated with pre-pandemic diabetes. Predictive margins were then calculated to obtain adjusted probabilities.

RESULTS: At follow-up, 1,076 participants (9.2%) reported Long COVID. In the unadjusted model, participants with pre-pandemic diabetes had a 36% higher risk of Long COVID compared with those without diabetes (RR = 1.36, 95% CI: 1.09-1.69, p = 0.006). After adjusting for age and sex, the relative risk increased to 1.43 (95% CI: 1.15-1.79, p = 0.002). In the fully adjusted model, which controlled for age, sex, ethnicity, education, income satisfaction, smoking, and other long-standing illness, the relative risk of Long COVID in participants with diabetes was 1.60 (95% CI: 1.27-2.02, p < 0.001). The adjusted predicted probability of long COVID was 14.4% (95% CI: 11.2-17.6) among those with diabetes, compared with 9.0% (95% CI: 8.5-9.5) among those without.

CONCLUSIONS: In this nationally representative prospective cohort, pre-pandemic diabetes emerged as an independent risk factor for Long COVID. Enhanced surveillance and targeted support for individuals with diabetes may be warranted in Long COVID care strategies.},
}

@article {pmid40979084,
year = {2025},
author = {Kent, DA and Villegas-Downs, M and Wilson, A and Krishnan, J and Gerald, L},
title = {Navigating the challenges of NT-proBNP result disclosure in clinical research.},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e176},
pmid = {40979084},
issn = {2059-8661},
abstract = {BACKGROUND: The Office of Human Research Protections and the National Academy of Sciences, Engineering, and Medicine (NASEM) recommend the return of individual research results (IRRs) to study participants as a strategy to build public trust in science. However, the feasibility of sharing IRRs is unclear. Within a National Institutes of Health (NIH) funded parent study about Long COVID, we embedded the My ILLInet RECOVER Return of Results study to explore clinician-level considerations (e.g., validity, actionability, recommendations for follow-up) about returning a clinically used biomarker for heart failure (N-terminal pro-B-type natriuretic peptide, (NT-proBNP) collected as part of the NIH RECOVER study protocol.

APPROACH: Clinicians participated in a three-phase modified Delphi process that sought their input to guide appropriate follow up recommendations the research team should provide to research participants with an abnormal NT-proBNP.

RESULTS: Clinicians agreed that NT-proBNP results could be returned to study participants. However, consensus was not reached on specific NT-proBNP thresholds that warrant immediate medical attention versus general follow-up.

DISCUSSION: Lack of clinical context presents a challenge in returning IRRs. Clinicians expressed concerns about the potential harm caused by misinformation or misinterpretation of these findings. While the NASEM report offers guidance on communicating IRRs, careful consideration is essential to ensure that clinical uncertainty is conveyed clearly, minimizing the risk of misinterpretation.

CONCLUSION: The feasibility of returning IRRs to study participants depends, in part, on sufficient clinical context for the information to be actionable.},
}

@article {pmid40978825,
year = {2025},
author = {Kouyoumdjian, JA and Yamamoto, LA and Graca, CR},
title = {Exploration of Intersections and Divergences of Long COVID and Chronic Fatigue Syndrome.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e90607},
pmid = {40978825},
issn = {2168-8184},
abstract = {BACKGROUND: Fatigue is the most common symptom of Long COVID (LC), defined by persistent or newly emerging symptoms that develop at least three months after an initial SARS-CoV-2 infection, in the absence of other identifiable cause. This study investigates the prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as a potential comorbidity of LC.

METHODS:  The study enrolled 37 adult controls with no documented SARS-CoV-2 infection and 32 individuals with a history of infection, categorized as LC-yes (with LC symptoms) and LC-no (without LC symptoms). ME/CFS diagnosis was based on the International Consensus Criteria (ICC).

RESULTS:  Among LC-yes cases, the most frequently reported symptoms included post-exertional malaise (PEM); neurosensory, perceptual, or motor disturbances; cognitive impairment; sleep disturbances; pain; impaired thermoregulation; and flu-like symptoms, all occurring significantly more than in the LC-no or control groups. All individuals in the LC-yes group reported PEM. ME/CFS was diagnosed in three LC-yes cases (18.8%), one LC-no case (6.7%), and four control subjects (10.8%), with no statistically significant differences observed among groups. Experiencing more than six symptoms during acute infection, such as fatigue, loss of taste or smell, headache, fever, cough, myalgia, sore throat, shortness of breath, rhinorrhea, and diarrhea, was associated with a twofold higher risk of developing LC.

CONCLUSION: A substantial proportion of LC-yes individuals experienced PEM; neurosensory, perceptual, or motor disturbances; cognitive impairment; and sleep disturbances, with rates significantly exceeding those in the LC-no and control groups. Nevertheless, only a minority of LC-yes cases (18.8%) satisfied criteria for the ME/CFS, and the prevalence did not significantly differ from LC-no and controls. These findings suggest that while many symptoms of LC overlap with those of ME/CFS, only a subset of LC cases meet established ME/CFS diagnostic criteria.},
}

@article {pmid40978720,
year = {2025},
author = {Wei, DJ and Chow, CW and Cheung, WYH and Yeung, WF and Cao, PH and Liong, C and Chen, HY and Zhang, S and Zhong, LLD},
title = {Electro-acupuncture for long COVID neuropsychiatric symptoms: study protocol for a prospective, randomized sham-controlled, patient-assessor-blinded clinical trial.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1620288},
pmid = {40978720},
issn = {2296-858X},
abstract = {INTRODUCTION: Patients recovering from long COVID often endure a spectrum of neuropsychiatric symptoms, including cognitive impairment, memory deficits, mood disturbances and sleep disorders, that significantly impact their quality of life. Acupuncture, particularly electroacupuncture, has shown promise in addressing these symptoms. Currently there is no high-quality clinical trial for acupuncture on long COVID neuropsychiatric symptoms.

METHODS AND ANALYSIS: In this 24 weeks, sham-controlled, patient-assessor-blinded randomized trial, 150 long COVID patients will be equally allocated to either an electroacupuncture group (EAG) or a sham control group (SCG). Each subject will receive a total of 32 intervention sessions over a 16 weeks intervention phase (two sessions each week) and will be followed up for an additional 8 weeks. Primary outcomes include changes in the Mini-Mental State Examination (MMSE) and the Chinese version of the Beck Depression Inventory (CBDI) scores. Secondary outcomes include the Insomnia Severity Index (ISI), Brief Fatigue Inventory-Taiwan (BFI-T), and the Short Form 12 (SF-12). All outcomes will be assessed at baseline and then at 4 weeks intervals during both the treatment and post-treatment periods.

DISCUSSION: This trial aims to generate robust clinical data on the therapeutic effects of electroacupuncture for long COVID. The anticipated results will clarify electroacupuncture's value as a therapeutic option for neuropsychiatric symptoms in long COVID patients, contributing to evidence-based practice in integrative medicine.},
}

@article {pmid40977575,
year = {2025},
author = {Ribeiro, A and Hadavi, S and Gall, N and Hadden, RDM and Serra, J},
title = {Microneurography Reveals Unmyelinated Small Nerve Fiber Dysfunction in Long COVID.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78045},
pmid = {40977575},
issn = {1531-8249},
abstract = {OBJECTIVE: To review the microneurography findings of long coronavirus disease 2019 (COVID) patients who presented to the clinic with multisystem involvement affecting neurological, cardiovascular, gastrointestinal, genitourinary, pulmonary, and immunological domains.

METHODS: We analyzed 36 consecutive long COVID patients using microneurography. We evaluated abnormalities in C nociceptors, including spontaneous activity, peripheral sensitization, multiple spikes, conduction failure, and alterations in activity-dependent slowing of conduction velocity. Sympathetic nerve fiber function was assessed using the recovery cycle of excitability. Results were compared with a large normative database.

RESULTS: The mean age was 40.9 ± 9.2 years (range 17-60 years), with a female predominance (30/36, 83.3%). Patients were seen from 15 to 61 months after onset of symptoms (35.7 ± 11.3 months). All patients presented with neuropathic symptoms, mainly pain and orthostatic intolerance. A total of 32 patients (88.9%) had objective electrophysiological abnormalities in peripheral C fibers, including spontaneous nociceptor activity (61.1%), peripheral sensitization (27.8%), and multiple spikes (11.1%). Long COVID patients also showed a significant shift in C nociceptor populations, with a higher prevalence of type 1B mechano-insensitive C nociceptors compared with healthy controls. Changes in activity-dependent slowing of conduction velocity differed in opposite directions between mechano-sensitive and mechano-insensitive C nociceptors. Postganglionic sympathetic fibers also showed abnormal recovery cycles with a lack of supernormality, suggesting impaired neuronal homeostasis.

INTERPRETATION: This study provides novel electrophysiological evidence linking small nerve fiber dysfunction to long COVID. These findings align with previous histological evidence of small nerve fiber loss, reinforcing the hypothesis that peripheral nerve dysfunction contributes to the multisystem symptoms of long COVID. ANN NEUROL 2025.},
}

@article {pmid40977216,
year = {2025},
author = {Hitch, D and Botha, T and Tesfay, F and Holton, S and Said, CM and Hensher, M and Richards, K and Angeles, MR and Bennett, CM and Pepin, G and Rasmussen, B and Nicola-Richmond, K},
title = {Impacts of long COVID on disability, function and quality of life for adults living in Australia.},
journal = {Australian journal of primary health},
volume = {31},
number = {},
pages = {},
doi = {10.1071/PY25033},
pmid = {40977216},
issn = {1836-7399},
mesh = {Humans ; *Quality of Life ; Male ; Australia/epidemiology ; Female ; *COVID-19/psychology/complications/epidemiology ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Persons with Disabilities/statistics & numerical data/psychology ; Aged ; Activities of Daily Living ; Disability Evaluation ; SARS-CoV-2 ; Young Adult ; },
abstract = {Background To describe the impact of long COVID on disability, function and quality of life among adults living in Australia. Method People aged >18years with a history of COVID-19 infection confirmed by polymerase chain reaction or rapid antigen test were eligible for this cross-sectional survey. The World Health Organization Disability Assessment Schedule 2.0 measured disability and function, and the 36-Item Short Form Health Survey assessed quality of life. Results Participants (n =121) reported significant functional impairment and reduced quality of life compared with established population norms for these outcome measures. Most (n =104, 86%) reported clinically significant disability and participation limitations in daily activities. Mean World Health Organization Disability Assessment Schedule 2.0 scores indicated higher levels of disability than 98% of the general population. The 36-Item Short Form Health Survey scores indicated lower quality of life across all domains, but particularly in relation to vitality and social functioning. Regression analysis found significant associations between the World Health Organization Disability Assessment Schedule 2.0 and 36-Item Short Form Health Survey scores, and vaccine dose number, comorbidities and self-rated recovery. Conclusion Long COVID is associated with significantly reduced function and quality of life, which are distinct outcomes requiring targeted assessment and intervention. The overall impact may be exacerbated in people with pre-existing comorbidities who are more susceptible to long COVID in the first place. The findings underscore the need for targeted rehabilitation and support services for people living in Australia with long COVID, and further longitudinal research to explore the long-term impact on disability and quality of life, and inform policy and healthcare service delivery.},
}

Humans
*Quality of Life
Male
Australia/epidemiology
Female
*COVID-19/psychology/complications/epidemiology
Cross-Sectional Studies
Middle Aged
Adult
*Persons with Disabilities/statistics & numerical data/psychology
Aged
Activities of Daily Living
Disability Evaluation
SARS-CoV-2
Young Adult

@article {pmid40976237,
year = {2025},
author = {Soria, B and Andreu, E and Gonzaga, A},
title = {Long COVID: Is mitochondria the target?.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2025.09.019},
pmid = {40976237},
issn = {1525-0024},
}

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

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

@article {pmid40973114,
year = {2025},
author = {Vassiliou, VS and Tsampasian, V and Luchian, ML and D'Ascenzi, F and D'Ascenzo, F and Dweck, MR and Escaned, J and Gati, S and Halle, M and Koskinas, KC and Neubeck, L and Papadakis, M and Petersen, SE and Ristic, A and Metra, M and Biondi-Zoccai, G},
title = {Cardiovascular disease prevention and management in COVID-19: a clinical consensus statement of the European Association of Preventive Cardiology, the European Association of Cardiovascular Imaging, the Association of Cardiovascular Nursing & Allied Professions, the European Association of Percutaneous Cardiovascular Interventions, and the Heart Failure Association of the ESC.},
journal = {European journal of preventive cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/eurjpc/zwaf540},
pmid = {40973114},
issn = {2047-4881},
abstract = {The coronavirus-associated disease 2019 (COVID-19) pandemic has posed significant challenges due to the complex interplay between SARS-CoV-2 infection and cardiovascular disease. COVID-19 can trigger and exacerbate cardiovascular complications, observed both during the acute phase of infection and in the post-acute phase, with some individuals developing long-term sequelae collectively termed Long COVID. Additionally, reinfection and adverse reactions to COVID-19 vaccines may contribute to cardiovascular events. This clinical consensus statement, developed by associations of the European Society of Cardiology, aims to provide a comprehensive overview of cardiovascular prevention strategies across all stages of COVID-19. These include addressing cardiovascular risk associated with acute infection, prior infection, Long COVID, reinfection, and post-vaccination events. Key recommendations focus on preventing and managing cardiovascular manifestations in patients with acute or prior COVID-19, implementing targeted cardiovascular rehabilitation, and introducing interventions to mitigate the severity of Long COVID. The document also emphasizes lifestyle modifications and personalized therapeutic approaches to enhance patient outcomes. Given the evolving nature of COVID-19 and its long-term cardiovascular implications, ongoing research is crucial to address existing knowledge gaps, optimize preventive strategies, and improve patient care. Future studies should prioritize the individualization of preventive measures for diverse populations, refine rehabilitation strategies, and advance long-term cardiovascular care, ensuring that evidence-based practices continue to evolve alongside emerging data.},
}

@article {pmid40971997,
year = {2025},
author = {Ibrahim, A and Cesari, M and Tang, Q and Aktan Süzgün, M and Brandauer, E and Holzknecht, E and Wachter, A and Anselmi, V and Heidbreder, A and Stefani, A and Högl, B},
title = {Sleep Architecture and REM Sleep Without Atonia in Post-COVID-19 Insomnia.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsaf257},
pmid = {40971997},
issn = {1550-9109},
abstract = {STUDY OBJECTIVES: Insomnia associated with COVID-19 infection is a common complaint in long-COVID. Studies to date have predominantly examined post-COVID-19 sleep disturbances with questionnaires. We aimed to investigate whether there are distinctive polysomnographic findings in post-COVID-19 insomnia compared to non-COVID-related chronic insomnia.

METHODS: We included 150 patients with chronic insomnia, stratified into three groups: post-COVID-19 insomnia (n = 50), chronic insomnia during the pandemic without a history of COVID-19 infection (n = 50), and pre-pandemic chronic insomnia (n = 50). All patients underwent one-night video-polysomnography (v-PSG). The sleep architecture, respiratory variables and REM sleep without atonia (RWA) were compared across the groups.

RESULTS: Classical polysomnographic variables showed no significant differences across groups with regard to total sleep time, sleep efficiency, sleep stage percentages, and the apnea-hypopnea index. Post-COVID-19 insomnia patients had significantly increased RWA at both the chin and the flexor digitorum superficialis (FDS) (p=.020 for both), and higher nocturnal heart rates (p=.046). Sleep-bout analysis indicated shorter sustained N3-sleep periods (p=.001) and longer onset to stable REM-sleep (p=.016) in the post-COVID-19 insomnia group. Although sleep transitions did not withstand multiple comparison corrections, they revealed a trend towards decreased N3-sleep continuity and increased probabilities of transitioning to lighter stages (N3 → N3: unadjusted-p=.012; REM → N1: unadjusted-p=.027) in the post-COVID-19 insomnia.

CONCLUSIONS: Classical PSG profile of post-COVID-19 insomnia does not differ from non-COVID-related chronic insomnia. However, subtle differences in RWA and sleep integrity suggest that post-COVID-19 insomnia is driven not merely by pandemic-related stress factors but by additional physiological alterations linked to viral CNS involvement.},
}

@article {pmid40966577,
year = {2025},
author = {León-Herrera, S and Gómez-Bravo, R and Sánchez-Castro, M and Pavlou, MAS and Fischer, VJ and Hutmacher, D and Haeck, L and Weber, N and Oliván-Blázquez, B and Magallón-Botaya, R and Benoy, C and Schneider, JG},
title = {Fasting and Caloric Restriction in Long COVID Syndrome: A Scoping Review of Interventions and Outcomes.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuaf141},
pmid = {40966577},
issn = {1753-4887},
support = {//FASTCOV/ ; //Ministry of Health and Social Security of Luxembourg/ ; },
abstract = {BACKGROUND: Since the emergence of COVID-19, many patients continue to experience symptoms beyond the acute phase, a condition now termed long COVID syndrome (LCS). The complexity of LCS, with its varied symptoms, makes diagnosis and treatment challenging. Recent evidence suggests that dietary approaches, such as fasting and caloric restriction, may help in management of these symptoms. However, research on these interventions remains limited and preliminary.

OBJECTIVES: In this review we aimed to explore existing studies on the impacts of fasting and caloric restriction for LCS management, focusing on how these approaches might alleviate symptoms through mechanisms like reduced inflammation, enhanced autophagy, and better metabolic health. Additionally, we examined intervention types, reported outcomes, and gaps in the research to guide future studies of LCS.

METHODS: A systematic search was conducted using databases like PubMed, Scopus, and ScienceDirect for studies published from 2019 to 2024, following the Arksey and O'Malley framework and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A range of study types, including case series, narrative reviews, randomized controlled trial protocols, and public guidance documents, were included. Data were descriptively compiled.

RESULTS: Eleven studies met inclusion criteria, covering interventions such as intermittent and prolonged fasting, as well as caloric restriction, with durations from days to weeks. Some reported benefits included reductions in fatigue, cognitive impairment, and inflammatory symptoms such as joint pain, muscle pain, or chest tightness. However, the findings reported here are preliminary and limited by small sample sizes, short follow-up, and varied protocols and outcomes, underscoring the need for further standardized research.

CONCLUSIONS: Fasting and caloric restriction have shown potential benefits in managing LCS symptoms like fatigue, cognitive decline, and inflammatory symptoms. Nonetheless, the diversity of study designs and outcomes necessitates more rigorous research to confirm the effectiveness and safety of interventions for LCS management. Future studies should focus on long-term effects and biological mechanisms and include broader, more diverse populations to enhance generalizability and support clinical guidance.},
}

@article {pmid40964918,
year = {2025},
author = {Woldegiorgis, M and Bloomfield, L and Korda, R and Cadby, G and Ngeh, S and Knight, P and Jardine, A and Maticevic, J and Armstrong, P and Effler, P},
title = {Factors associated with persistence or recovery from long COVID six months post SARS-CoV-2 infection.},
journal = {Epidemiology and infection},
volume = {},
number = {},
pages = {1-18},
doi = {10.1017/S0950268825100551},
pmid = {40964918},
issn = {1469-4409},
}

@article {pmid40964469,
year = {2025},
author = {Pearson, L and Maina, A and Compratt, T and Harden, S and Aaroe, A and Copas, W and Thompson, L},
title = {Correction: Stellate Ganglion Block Relieves Long COVID-19 Symptoms in 86% of Patients: A Retrospective Cohort Study.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {c295},
doi = {10.7759/cureus.c295},
pmid = {40964469},
issn = {2168-8184},
abstract = {[This corrects the article DOI: 10.7759/cureus.45161.].},
}

@article {pmid40959166,
year = {2025},
author = {Tankéré, P and Lajeune, E and Mariet, AS and Cottenet, J and Beltramo, G and Georges, M and Bonniaud, P and Favrolt, N and Quantin, C},
title = {Long-term in-hospital mortality and chronic thromboembolic pulmonary hypertension after COVID-19-associated pulmonary embolism in France: a nationwide study.},
journal = {ERJ open research},
volume = {11},
number = {5},
pages = {},
pmid = {40959166},
issn = {2312-0541},
abstract = {BACKGROUND: Although long-term effects of coronavirus disease-2019 (COVID-19) such as dyspnoea are frequent, the mechanisms are often poorly understood. The endothelial effects of COVID-19, such as venous or arterial thrombosis, are also well documented. Thus, the incidence of chronic thromboembolic pulmonary hypertension (CTEPH) following COVID-19 is an issue with many implications, particularly for screening in patients with long COVID.

METHODS: From the French National Hospital Discharge database (March 2020 to December 2021), we included all adults hospitalised for pulmonary embolism (PE). To study the hospital incidence of CTEPH, we excluded patients with previous pulmonary hypertension diagnoses. Then, in the 2 years following the admission for PE, we compared the hospital incidence of CTEPH between PE patients with COVID-19 (COVID-PE) and without (non-COVID-PE). We also studied in-hospital mortality.

RESULTS: Among the 136 505 patients included, 1.68% were diagnosed with CTEPH in the following 2 years with a significant difference between COVID-PE and non-COVID-PE (0.77% versus 1.82%; p<0.0001). The 2-year in-hospital mortality was significantly lower in COVID-PE than in non-COVID-PE (4.82% versus 13.34%; p<0.0001). These results were confirmed by multivariate analyses. Among COVID-PE, we found no difference in the hospital incidence of CTEPH between 2020 and 2021, while after the initial discharge, in-hospital mortality was significantly higher in 2020 compared with 2021.

CONCLUSION: When investigating chronic dyspnoea in patients hospitalised for COVID-19 associated with PE, the risk of CTEPH should not be considered higher than for other PE. COVID-19 associated with hospitalised PE should not be considered an additional harmful factor if not associated with initial in-hospital mortality.},
}

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

@article {pmid40960332,
year = {2023},
author = {Kim, S and Hillery, T and Suric, V and Kim, C},
title = {Stellate Ganglion Block for Refractory Post-COVID Headache: Case Report.},
journal = {Pain medicine case reports},
volume = {7},
number = {2},
pages = {73-76},
pmid = {40960332},
issn = {2768-5152},
abstract = {BACKGROUND: Long coronavirus disease (COVID) is a multitude of symptoms weeks to months after recovering from COVID 2019 (COVID-19) and involves a variety of symptoms, ranging from brain fog and fatigue to refractory headaches that may result in ongoing disability.

CASE REPORT: A 49-year-old man presents for persistent headaches following COVID-19 infection months prior. The pain was frontal and bilateral but more prominent on the right, without sensitivity to light nor sound, and without identifiable triggers. He trialed numerous medications without relief. He rated his pain on average 8-10 on the Visual Analog Scale (VAS). After discussion of options, the patient elected to proceed with a stellate ganglion block (SGB). The patient underwent a right-sided SGB with 5 mL of 0.25% bupivacaine. Following the injection, the patient noted ~50% benefit immediately. On 6-week follow-up, he noted improvement of his headaches to 1-2 on the VAS. At 4 months, the headaches continued to be controlled (1-2 on the VAS).

CONCLUSIONS: Reports suggest that symptoms from long COVID are caused by dysregulation of the sympathetic nervous system. We report the use of the SGB for treating refractory headaches related to long COVID, suggesting that the SGB may relieve the dysautonomia.},
}