@article {pmid42051331,
year = {2026},
author = {Wilches-Luna, EC and Perez-Hortúa, V and Asencio-Santofimio, H and Aguilar-Zambrano, J and Arzayus-Patiño, L},
title = {Distribution of pulmonary ventilation in women with post-COVID-19 before and after the use of a respiratory incentive device (UBICU): a pilot study.},
journal = {Frontiers in digital health},
volume = {8},
number = {},
pages = {1789878},
pmid = {42051331},
issn = {2673-253X},
abstract = {INTRODUCTION: In the aftermath of the COVID-19 pandemic, restrictive pulmonary complications have emerged as a common long-term sequela. To address these impairments, a novel flow-based respiratory incentive device, UBICU, was developed to promote lung expansion through gamification and visual feedback. The aim of this study was to describe the pulmonary ventilation distribution using Electrical Impedance Tomography (EIT) in women with long COVID and restrictive pulmonary impairment, before and after using the UBICU device.

METHODS: This exploratory (pre-post) pilot study included eight women with post-COVID-19 restrictive impairment, as determined by spirometry in accordance with ATS/ERS guidelines. Pulmonary ventilation distribution was assessed before and after the intervention using electrical impedance tomography. Participants were provided with the UBICU device and instructed to perform three sets of 10 repetitions daily for seven consecutive days. The study was approved by the Institutional Ethics Committee, adhered to the principles of the Declaration of Helsinki, and written informed consent was obtained from all participants.

RESULTS: An asymmetric regional ventilation pattern was observed before and after the intervention. Statistically significant improvements were found in ROI 1 (p = 0.007), ROI 3 (p = 0.007), and ROI 4 (p = 0.007) after using the UBICU device.

CONCLUSION: Use of the UBICU device was associated with improvements in pulmonary ventilation distribution, suggesting its potential as an adjunctive therapeutic tool in the management of women with long COVID and restrictive pulmonary impairment.},
}

@article {pmid42051540,
year = {2026},
author = {Jin, H and An, Y and Huang, J and Luo, T and Wu, X},
title = {Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1774310},
pmid = {42051540},
issn = {1664-3224},
mesh = {Humans ; *COVID-19/immunology/complications/metabolism/physiopathology ; *SARS-CoV-2 ; *Fatigue Syndrome, Chronic/immunology/physiopathology/metabolism ; Exercise/physiology ; Mitochondria/metabolism ; Neuroimmunomodulation ; Post-Acute COVID-19 Syndrome ; Reactive Oxygen Species/metabolism ; },
abstract = {Post-exertional malaise (PEM) is a common core symptom in various chronic debilitating conditions, such as Post COVID-19 Condition (PCC, also known as Long COVID) and Chronic Fatigue Syndrome (CFS). It is characterized by the delayed and persistent exacerbation of symptoms following even mild physical or cognitive activities. This review presents a systematic review of the pathophysiological mechanisms involved in PEM, proposing a dynamic framework of multi-system interactions that may lead to homeostatic imbalance. The etiology of PEM is multifactorial, potentially involving factors such as the persistent presence of pathogens, exposure to environmental toxins, and genetic predisposition. Collectively, these factors may establish a vulnerable baseline that heightens the body's physiological response to stressors, such as exercise, potentially triggering a pathological reaction. First, mitochondrial dysfunction and metabolic abnormalities may act as potential initiating factors in PEM, manifesting as impaired ATP synthesis, overproduction of reactive oxygen species (ROS), and the accumulation of metabolic byproducts. It is crucial to emphasize that exercise itself induces a 'toxic excitatory effect,' whereby healthy individuals enhance mitochondrial function and antioxidant defenses through physical activity. However, in individuals predisposed to PEM, due to underlying pathological conditions (e.g., sequelae of viral infections), this adaptive process is disrupted, preventing effective restoration of mitochondrial homeostasis and may initiate a potential vicious cycle of dysfunction. Second, ROS and mitochondrial DNA (mtDNA), as damage-associated molecular patterns (DAMPs), along with pathogen-associated molecular patterns (PAMPs), may activate the NLRP3 inflammasome and induce the release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, potentially transforming localized metabolic stress into a systemic inflammatory response. Subsequently, peripheral inflammation may be transmitted to the central nervous system through disruption of the blood-brain barrier and vagal nerve pathways, activating glial cells and initiating neuroinflammation. This process may ultimately affect the brain's interoceptive network, particularly the insular cortex, resulting in altered perception and processing of signals related to fatigue and pain. Furthermore, mitochondrial dysfunction in neurons may contribute to central energy depletion, which may impair synaptic plasticity and induce cognitive deficits and brain fatigue. Ultimately, this review proposes that PEM may arise from a complex interplay among mitochondrial dysfunction, immune activation, and neuroinflammation, which together form a self-perpetuating loop of "energy exhaustion - inflammation amplification," potentially contributing to the chronic and multi-system nature of PEM symptoms. The integrated "metabolism-immune-neuro" interaction model presented in this article may provide a potential comprehensive framework for understanding PEM and highlights the need for a multi-target, collaborative intervention approach that may help disrupt the pathological cycle.},
}

Humans
*COVID-19/immunology/complications/metabolism/physiopathology
*SARS-CoV-2
*Fatigue Syndrome, Chronic/immunology/physiopathology/metabolism
Exercise/physiology
Mitochondria/metabolism
Neuroimmunomodulation
Post-Acute COVID-19 Syndrome
Reactive Oxygen Species/metabolism

@article {pmid42052332,
year = {2025},
author = {Lee, EJ and Tsang, C and Pérez, MLG and Abouzari, M and Djalilian, HR},
title = {Calcitonin Gene-Related Peptide-Induced Central Sensitization: A Hypothesis for Long COVID Symptoms.},
journal = {Medical hypotheses},
volume = {195},
number = {},
pages = {},
pmid = {42052332},
issn = {1532-2777},
abstract = {Central sensitization (CS) denotes aberrant processing of sensory stimuli within the central nervous system, wherein innocuous inputs activate pain pathways, leading to pain hypersensitivity. Features observed in CS conditions are often present in patients with long COVID, suggesting a potentially shared pathophysiological mechanism. We hypothesize that elevated levels of calcitonin gene-related peptide (CGRP), a neuropeptide known to play an integral role in the development of CS, may contribute to the persistent symptoms observed in long COVID. This article explores the role of CGRP within the context of CS and proposes its potential relationship to long COVID.},
}

@article {pmid42052381,
year = {2026},
author = {Lin, J and Chen, S and Zhang, L and Qiu, M and Zuo, W and Wang, L and He, Q and Li, Y and Jin, H and Tan, S and Huang, M and Zhu, C and Jin, Q and Wang, M and Wan, Y and Hu, B},
title = {Two-year trajectory of cognitive decline and neurological sequelae in COVID-19 survivors with acute neurological symptoms.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1724803},
pmid = {42052381},
issn = {1663-4365},
abstract = {INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 has profound implications for global public health. It significantly affects the nervous system and cognitive function. The emergence of long COVID has raised concerns regarding long-term cognitive impairment, particularly among patients who experienced neurological symptoms during the acute phase of infection.

AIM: This study investigated the impact of neurological symptoms during acute SARS-CoV-2 infection on subsequent cognitive change and neurological sequelae over a 2-year period.

METHODS: We enrolled 3,419 hospitalized patients with confirmed infection in Wuhan, China (Dec 2022-Mar 2023), and 2,087 completed follow-ups. Propensity score matching identified 901 patients with acute neurological symptoms and 901 controls. Cognitive decline was measured with the Informant Questionnaire on Cognitive Decline in the Elderly, and cognitive status with the Telephone Interview of Cognitive Status-40. Multivariable regression was used to examine risk factors and cognitive changes, and residual neurological symptoms and new-onset symptoms were also analyzed.

RESULTS: Acute neurological symptoms, particularly central nervous system manifestations such as delirium and brain fog, were strongly associated with both cognitive decline (aOR, 2.16; 95% CI, 1.53-3.07) and cognitive impairment (aOR, 2.75; 95% CI, 1.73-4.49). Delirium, brain fog, stroke, numbness, and facial paralysis were associated risk factors (all p < 0.05). After 2 years' follow-up, most acute neurological symptoms had subsided, yet fatigue (8.66%) and brain fog (5.99%) persisted. Comorbidities did not significantly increase the risk of persistent symptoms. For the new-onset symptoms, the proportion of insomnia, tinnitus, blurred vision, movement disorder, palpitation, muscle weakness, and respiratory symptoms were much higher in the neurological symptom group (p < 0.05), with a highest proportion in insomnia (9.99% vs. 5.22%, p < 0.001), compared with the non-neurological symptom group.

CONCLUSION: Acute neurological symptoms, especially central nervous system manifestations, were strongly associated with long-term cognitive decline and new-onset symptoms (mainly insomnia) in COVID-19 survivors. This study uniquely reveals the persistence of high levels in brain fog and fatigue at 2-year's follow up, despite overall subsidence of most acute manifestations, underscoring the need for early intervention and sustained monitoring in this high-risk population.},
}

@article {pmid42052408,
year = {2026},
author = {Wang, R and Dai, R and Dai, H and French, E and Zheng, C},
title = {Controlling FDR in selecting group-level simultaneous signals from multiple data sources with application to the National COVID Collaborative Cohort data.},
journal = {Journal of applied statistics},
volume = {},
number = {},
pages = {},
pmid = {42052408},
issn = {0266-4763},
abstract = {One challenge in exploratory association studies using observational data is that the associations between the predictors and the outcome are potentially weak and rare, and the candidate predictors have complex correlation structures. False discovery rate (FDR) controlling procedures can provide important statistical guarantees for replicability in predictor identification in exploratory research. In the recently established National COVID Collaborative Cohort (N3C), electronic health record (EHR) data on the same set of grouped candidate predictors are independently collected in multiple different data contributing sites, offering opportunities to identify true associations by combining information from different sources. One challenge is to handle the heterogeneous data types for the same clinical endpoint from the multiple sites. This paper addresses this challenge by presenting a general knockoff-based variable selection algorithm to identify associations from unions of group-level conditional independence tests (simultaneous signals) with exact FDR control guarantees under finite sample settings. This algorithm can work with general regression settings, allowing heterogeneity of both the predictors and the outcomes across multiple data sources. We demonstrate the performance of this method with extensive numerical studies and an application to the N3C data.},
}

@article {pmid42053865,
year = {2026},
author = {Mignolet, M and Deroux, C and Florkin, T and Bielarz, V and De Swert, K and Halloin, N and Sprimont, L and Ladang, A and George, F and Gilloteaux, J and Abeloos, L and Garin, P and Van Weyenbergh, J and Jamoulle, M and Diederich, C and Gillet, NA and Bulpa, P and Nicaise, C},
title = {Pathogenic IgG from long COVID patients with neurological sequelae triggers sensitive but not cognitive impairments upon transfer into mice.},
journal = {Acta neuropathologica},
volume = {151},
number = {1},
pages = {},
pmid = {42053865},
issn = {1432-0533},
mesh = {Animals ; *COVID-19/immunology/complications/psychology ; *Immunoglobulin G/immunology ; Mice ; Humans ; Male ; Female ; Mice, Inbred C57BL ; *Cognitive Dysfunction/immunology/etiology ; Middle Aged ; *Autoantibodies/immunology ; SARS-CoV-2 ; Hyperalgesia/immunology ; Disease Models, Animal ; Adult ; Aged ; },
abstract = {Approximately 30% of long COVID patients still experience neurological symptoms (brain fog, pain, chronic fatigue) more than 4 months after the onset of COVID-19. This condition, known as 'neurological long COVID', remains poorly understood and might be explained by a persisting autoimmune response against nervous-derived self-antigens. The aim of this study is to determine whether IgG autoantibodies from long COVID patients with neurological sequelae can bind to central or peripheral nervous system epitopes and trigger neuropsychiatric symptoms upon passive transfer into mice, thereby mirroring patient-reported manifestations. Long COVID patients meeting the 2021 consensus WHO definition were included following a standardized neuropsychological assessment, while excluding patients with a medical history of autoimmune and neurological disorders. Age- and sex-matched asymptomatic individuals were used as healthy controls. Total IgGs were isolated using protein G purification and injected intraperitoneally into C57Bl6/J mice for four consecutive days. During the two weeks post-injections, behavioral tests assessed mechanical allodynia, thermal hyperalgesia, spatial working memory, depression, and anxiety. Mice injected with IgG from long COVID patients showed no difference with the control group in terms of anxiety or depression behaviors, short- or long-term spatial memories. However, they displayed a transient decrease of paw withdrawal threshold and thermal hypersensitivity during the first week. This effect was abolished when IgG-depleted serum or papain-digested IgGs were transferred. IgG from long COVID patients accumulated in the lumbar dorsal root ganglia of injected mice and colocalized with proprioceptive and nociceptive sensory neurons, without inducing local neuroinflammation or astrogliosis. When applied onto human post-mortem DRG tissue, patient-derived IgG also exhibited immunoaffinity for sensory neuron somata. These data demonstrate that IgGs from long COVID patients bind to peripheral sensory neurons and induce pain-related symptoms in mice. Our findings also support the hypothesis that autoantibodies mediate pain-related pathophysiology in the spectrum of long COVID symptoms.},
}

Animals
*COVID-19/immunology/complications/psychology
*Immunoglobulin G/immunology
Mice
Humans
Male
Female
Mice, Inbred C57BL
*Cognitive Dysfunction/immunology/etiology
Middle Aged
*Autoantibodies/immunology
SARS-CoV-2
Hyperalgesia/immunology
Disease Models, Animal
Adult
Aged

@article {pmid42055117,
year = {2026},
author = {Kahlon, RK and Laurin, JKH and Nath, E and Raj, SR},
title = {Successful Ivabradine Use Throughout Pregnancy for Postural Orthostatic Tachycardia Syndrome: A Case Report with Reassuring Maternal-Fetal Outcomes.},
journal = {The Canadian journal of cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cjca.2026.04.019},
pmid = {42055117},
issn = {1916-7075},
abstract = {We report on a 35-year-old gravida 2 para 1 female with long-COVID postural orthostatic tachycardia syndrome (POTS) who continued all pharmacologic therapies from preconception through delivery, including ivabradine, a medication contraindicated in pregnancy due to preclinical embryotoxicity and teratogenicity. Serial fetal assessments including growth studies, fetal Dopplers, and non-stress tests remained normal throughout gestation without evidence of fetal bradycardia, arrhythmia, or structural abnormalities. Delivery at 38 weeks 5 days' gestation resulted in a healthy female neonate. This case illustrates successful use of off-label ivabradine in pregnancy with reassuring maternal-fetal outcomes under close obstetric-cardiology supervision.},
}

@article {pmid42055743,
year = {2026},
author = {Grach, SL and Seltzer, J and Mueller, MR and Aakre, CA and Natividad, LT and Lawson, DK and Ganesh, R and Hurt, RT},
title = {Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation.},
journal = {Annals of family medicine},
volume = {},
number = {},
pages = {},
doi = {10.1370/afm.250266},
pmid = {42055743},
issn = {1544-1717},
abstract = {PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem neurologic disease characterized by profound fatigue and decreased functional capacity, postexertional malaise, and unrefreshing sleep, along with cognitive impairment and/or orthostatic intolerance. Its prevalence has risen exponentially with the COVID-19 pandemic. Pharmacologic therapies have been used successfully by ME/CFS specialists but may be underused by the general medical field.

METHODS: To assess this potential practice gap, we retrospectively analyzed the records of 571 patients with an ME/CFS diagnosis referred to our ME/CFS specialty clinic in Minnesota during 2018-2022. We ascertained medications that had already been tried at the time of consultation and also ascertained supplement use.

RESULTS: With the exception of medications primarily used for pain and anxiety, use of pharmacotherapy for ME/CFS symptom management as proposed by specialists was limited. Overall, 68.3% of patients had had at least 1 medication potentially prescribed for ME/CFS; the most common were serotonin-norepinephrine reuptake inhibitors, gabapentin, and tricyclic antidepressants. A slightly larger share of patients, 72.2%, reported having taken at least 1 dietary supplement; the most common were vitamin D, vitamin B12 and B complex, and fish oil.

CONCLUSION: Our findings suggest that potentially helpful medications for ME/CFS are being underprescribed in the general medical field and that patients may resort to supplements to manage symptoms. Better education of clinicians about available treatment options and treatment guides may improve management of this debilitating disease.},
}

@article {pmid42056279,
year = {2026},
author = {Faghy, MA and Wüst, RCI and Altmann, DM and Ashton, RE and McMullen, SB and Duncan, R and Ewing, AG and Hausmann, E and Gupta, S and Hornig, M and Joffe, D and Kane, B and Khan, MA and Natt, M and Owen, R and Putrino, D and Skipper, L and Taylor, C and Thomas, C and Tuller, D and Beckman, D and Kruger, A and Pretorius, E},
title = {Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID.},
journal = {Communications medicine},
volume = {6},
number = {1},
pages = {},
pmid = {42056279},
issn = {2730-664X},
abstract = {BACKGROUND: Viral and infectious illnesses can exert profound and enduring effects on population health and well-being. In the aftermath of SARS-CoV-2 infection, post-acute sequelae, collectively referred to as Long COVID, have emerged as a major global health challenge, affecting more than 400 million people and contributing to estimated annual economic costs exceeding $1 trillion.

SCOPE OF THE REVIEW: Long COVID encompasses a wide and heterogeneous spectrum of debilitating symptoms, including cognitive dysfunction, sleep disturbances, severe fatigue, and post-exertional malaise. Despite its substantial burden, fundamental uncertainties remain regarding its underlying pathophysiology, the development of robust diagnostic criteria, and the identification of effective therapeutic options.

KEY INSIGHTS: This review synthesises current evidence on the biological mechanisms thought to contribute to Long COVID, spanning immune dysregulation, viral persistence, autonomic dysfunction, microvascular pathology, and other emerging hypotheses. We examine advances and limitations in contemporary diagnostic approaches and critically appraise existing treatment strategies, highlighting inconsistencies and gaps that hinder clinical consensus.

IMPLICATIONS: By integrating interdisciplinary insights, this review underscores the urgent need for mechanistic clarity, validated diagnostic frameworks, and rigorously evaluated treatment pathways. Addressing these gaps will be essential to developing effective, evidence-based management strategies and mitigating the long-term impact of Long COVID on global health.},
}

@article {pmid42046713,
year = {2026},
author = {Wu, KK and Deng, JS and Jiang, PL and Huang, CL and Tung, TH and Zhu, JS},
title = {Prevalence and influencing factors of long COVID brain fog among college students: a cross-sectional study in Taizhou, China.},
journal = {PeerJ},
volume = {14},
number = {},
pages = {e21026},
pmid = {42046713},
issn = {2167-8359},
mesh = {Humans ; Cross-Sectional Studies ; China/epidemiology ; *COVID-19/epidemiology/complications ; Male ; Female ; *Students/statistics & numerical data/psychology ; Prevalence ; Young Adult ; Universities ; SARS-CoV-2 ; Adult ; Surveys and Questionnaires ; Adolescent ; Risk Factors ; },
abstract = {BACKGROUND: Long COVID following SARS-CoV-2 infection is a public health concern. Brain fog, a symptom of long COVID, has an impact on patients' daily lives and health. However, studies on the effects of COVID on college students are limited.

METHODS: This cross-sectional study included students from two tertiary institutions in Taizhou, China. Data were collected using WeChat-based electronic questionnaires on the Wen-Juan-Xing survey platform from July 20, 2023 to August 7, 2023. Chi-square analyses and binary logistic regression were used to evaluate the factors contributing to brain fog.

RESULTS: A total of 1,071 students participated in the survey. Of these 1,071 students, 13.7% (147/1,071) reported experiencing long COVID, of whom 27.2% (40/147) reported symptoms of brain fog. Significant associations with brain fog were observed for the following factors: age (> 20 vs. ≤ 20 years, odds ratio (OR) = 4.360, 95% confidence interval (CI) [1.620-11.740]), clinical classification of COVID-19 (OR = 2.940, 95% CI [1.230-7.010]), and a decreased sense of smell and taste (OR = 5.110, 95% CI [1.240-21.110]).

CONCLUSIONS: This study highlights the significant prevalence of long COVID brain fog among college students and identifies key associated factors, underscoring the need for specific, focused interventions and support for affected individuals.},
}

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

@article {pmid42046721,
year = {2026},
author = {Deng, M and Wang, Y},
title = {Ocular Symptoms in Long COVID: A Cross-Sectional Study [Letter].},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {616430},
pmid = {42046721},
issn = {1177-5467},
}

@article {pmid42040088,
year = {2026},
author = {Onik, G},
title = {A health resort-based intervention reduces insomnia with minimal changes in quality of life in COVID-19 survivors and non-COVID-19 controls.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1803380},
pmid = {42040088},
issn = {2296-2565},
mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy ; *Quality of Life ; *COVID-19/complications/psychology ; Male ; Female ; Middle Aged ; *Health Resorts ; Adult ; *Survivors/psychology/statistics & numerical data ; Aged ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Persistent post-COVID-19 symptoms, especially insomnia, are common and markedly impair quality of life. While some patients improve over time, many experience long-lasting complaints. Health resort treatment has shown potential benefits in long COVID, but its effects on sleep and quality of life remain unclear. This study aimed to evaluate the impact of comprehensive health resort treatment on insomnia and quality of life in post-COVID-19 individuals and to compare outcomes with those without prior SARS-CoV-2 infection.

METHODS: A total of 101 participants, including 30 post-COVID-19 individuals, underwent comprehensive health resort treatment. Propensity score matching was used to compare post-COVID-19 and non-COVID groups. Insomnia and health-related quality of life were assessed using the Athens Insomnia Scale and EQ-5D-5L, respectively, before and after the sanatorium stay.

RESULTS: The Athens Insomnia Score significantly decreased in post-COVID-19 individuals following sanatorium treatment (6.24 ± 5.93 vs. 3.97 ± 4.19 points; p = 0.0005). The EQ index did not change significantly after treatment (p = 0.08). Overall health status, assessed using the visual analog scale (VAS), significantly improved in individuals with a history of COVID-19 (76.03 ± 12.70 vs. 88.45 ± 7.80 points; p < 0.0001). Treatment effectiveness did not differ significantly between the patient groups.

CONCLUSIONS: Comprehensive health resort treatments may improve insomnia and self-reported health in COVID-19 survivors. Effects on overall quality of life appear limited, and outcomes are similar to those in individuals without prior COVID-19. Further research is needed to clarify the clinical utility of this approach.},
}

Humans
*Sleep Initiation and Maintenance Disorders/therapy
*Quality of Life
*COVID-19/complications/psychology
Male
Female
Middle Aged
*Health Resorts
Adult
*Survivors/psychology/statistics & numerical data
Aged
SARS-CoV-2

@article {pmid42040552,
year = {2026},
author = {Srinivasan, M and Joseph, PV},
title = {A hypothesis connecting dysgeusia due to defects in ATP-P2X3 signaling and fatigue in myalgic encephalomyelitis/chronic fatigue syndrome: lessons learned from long-COVID.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1808646},
pmid = {42040552},
issn = {2296-858X},
abstract = {Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a neuroimmune disease characterized by debilitating post-exertional malaise (PEM), brain-fog/cognitive problems, and dysregulation of the autonomic nervous system. Currently, there are no objective biomarkers for ME/CFS despite decades of research. Here, we compile evidence from literature that supports taste dysfunction, particularly alterations of taste perception mediated by Type II taste receptor cells, may be a critical underrecognized feature of ME/CFS. The impetus is drawn from the emerging evidence of clinicopathological similarities between long-COVID and ME/CFS. We discuss in parallel the mechanisms of cellular metabolism, inflammation, vascular dysfunction, and autonomic dysregulation in ME/CFS and long-COVID pathophysiology. We postulate that mechanistically, dysregulation of ATP signaling through P2X2/P2X3 purinergic receptors underlies both gustatory impairment and core ME/CFS symptoms. Adopting information from the NIH-RECOVER shared resources, we present evidence that suggests chemosensory dysfunction as a potential indicator of progression/severity of PEM. We discuss standardized taste testing as a non-invasive screening tool complementary to molecular biomarkers for ME/CFS. Notwithstanding, we acknowledge the limitations, confounding and contributing factors such as medications and deficiencies that may exacerbate or independently cause taste-related symptoms in ME/CFS. In conclusion, we present a compelling case for the multi-factorial role of taste dysfunction in ME/CFS and suggest specific research priorities for investigating the relationship between chemosensory function and post-viral chronic illness.},
}

@article {pmid42041273,
year = {2026},
author = {Silveira, JM and Nakaishi, APM and da Silva, MG and Dos Santos, DO and Gastaldi, AC},
title = {Effects of Exercise-Based Pulmonary Rehabilitation in Patients with Long COVID: A Systematic Review and Meta-Analysis.},
journal = {Advances in respiratory medicine},
volume = {94},
number = {2},
pages = {},
doi = {10.3390/arm94020025},
pmid = {42041273},
issn = {2543-6031},
mesh = {Humans ; *COVID-19/rehabilitation/complications/physiopathology ; *Exercise Therapy/methods ; Quality of Life ; Exercise Tolerance ; SARS-CoV-2 ; Randomized Controlled Trials as Topic ; },
abstract = {Background/Objective: A substantial proportion of infected individuals develop persistent symptoms after the acute phase of COVID-19, regardless of initial disease severity. Long COVID (LC) remains a public health challenge characterized by impaired functional exercise capacity (FEC) and quality of life (QoL). We systematically synthesized evidence on the effects of in-person outpatient pulmonary rehabilitation (OPR) with individualized and supervised exercise in adults with LC. Methods: Following PROSPERO (CRD42023389365), this study reviewed randomized controlled trials (RCTs) and observational cohort studies (OCSs) published between November 2019 and January 2026 in MEDLINE/PubMed, Web of Science, PEDro, and EMBASE. Results: Fifteen studies (n = 803) were included. OPR improved FEC (6MWT; MD: 53.72 m, 95% CI 43.69-63.75) and 30″SST (MD: 4.68, 95% CI 3.59-5.77) and reduced exertional dyspnea. RCTs showed benefits in physical (MD: 8.04, 95% CI 3.02-13.05) and mental QoL (MD: 6.60, 95% CI 2.01-11.18) and dyspnea impact, with inconsistent PF findings. Fatigue showed a trend toward improvement but was measured using heterogeneous patient-reported tools in RCTs and OCSs. Conclusions: Supervised PR improves FEC, QoL, and dyspnea in individuals with LC. In patients with fatigue/PEM, systematic assessment and continuous symptom monitoring are essential. High-quality controlled studies are needed to strengthen evidence and clinical guide.},
}

Humans
*COVID-19/rehabilitation/complications/physiopathology
*Exercise Therapy/methods
Quality of Life
Exercise Tolerance
SARS-CoV-2
Randomized Controlled Trials as Topic

@article {pmid42041818,
year = {2026},
author = {Moore, AL and Jedlicka, EJ and Patterson, JC and Ledbetter, CR},
title = {LearningRx Cognitive Training for Workplace Self-Efficacy in Adults with Post-COVID-19 Brain Fog: A Mixed-Methods Pilot Study.},
journal = {Brain sciences},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/brainsci16040410},
pmid = {42041818},
issn = {2076-3425},
support = {Louisiana State University Health Sciences Center Shreveport Research Council Intramural Grants Program Center for Brain Health (CBH) Grant-in-Aid Award.//Louisiana State University/ ; },
abstract = {BACKGROUND/OBJECTIVES: Cognitive dysfunction, or "brain fog", following COVID-19 viral infection is strongly associated with diminished work capacity which disproportionality affects working-age adults. This study examined an existing method of cognitive rehabilitation training applied to adults struggling with workplace functioning and self-efficacy due to post-COVID-19 brain fog.

METHODS: Nine adults with post-COVID-19 cognitive dysfunction participated in this single arm pilot trial of a severity-adaptive cognitive training program. The participants completed 45-90 h of clinician-delivered cognitive training exercises delivered remotely in 60- to 90-min sessions, two or three times per week. The primary outcome measure was overall workplace self-efficacy with subskills of perceived workplace functioning, perception of cognitive functioning, and perception of home functioning assessed through pre and post surveys and qualitative interviews. The secondary outcome was cognitive function operationalized by an IQ score administered before and after the intervention.

RESULTS: The participants achieved significant improvements in workplace self-efficacy and cognition following cognitive training. The main qualitative themes of self-reported improvements were in executive function, health and energy, daily living activities, productivity, and socioemotional functioning. A cross-case synthesis of pre-intervention struggles, and post-intervention improvements revealed subthemes at work or school in cognitive processing and comprehension, memory, executive function, fatigue, emotional distress, confidence in work or academics, and work/academic performance impairment. As a group, the mean gain in IQ score was 10.5 points.

CONCLUSIONS: This study adds to the growing body of literature examining the possibility of using cognitive rehabilitation for post-COVID-19 cognitive dysfunction impacting workplace self-efficacy and work functioning.},
}

@article {pmid42043247,
year = {2026},
author = {Mahajan, S and Mahajan, S and Kaushik, N},
title = {Integrative Insights into the Immunopathogenesis and Organ-Specific Immunological Mechanisms of Long COVID: A Narrative Review.},
journal = {Viruses},
volume = {18},
number = {4},
pages = {},
doi = {10.3390/v18040458},
pmid = {42043247},
issn = {1999-4915},
mesh = {Humans ; *COVID-19/immunology/pathology/complications/virology ; *SARS-CoV-2/immunology ; Post-Acute COVID-19 Syndrome ; Immunity, Innate ; Adaptive Immunity ; Organ Specificity ; Autoimmunity ; },
abstract = {Long COVID (LC), also referred to as post-acute sequelae of SARS-CoV-2 infection, is characterized by persistent symptoms originating 3 months following acute COVID-19, lasting for at least two months and frequently affecting individuals who initially experienced mild to moderate disease. The clinical spectrum is heterogeneous, involving respiratory, cardiovascular, neurological, renal, gastrointestinal, and endocrine systems, thereby posing substantial diagnostic and therapeutic challenges. Despite extensive investigation, the precise immunopathogenic mechanisms underlying LC remain incompletely defined. Accumulating evidence suggests that LC is driven by a multifactorial interplay of persistent viral antigen reservoirs, chronic immune activation, dysregulated innate and adaptive immune responses, autoimmunity, endothelial dysfunction, microvascular injury, and aberrant tissue repair. These systemic immune perturbations manifest variably across different organs, contributing to the diverse clinical phenotypes observed. However, mechanistic clarity is hindered by heterogeneity in study designs, limited longitudinal data, and the absence of standardized immunological profiling. This narrative review provides integrative insights into the immunopathogenesis of LC, synthesizing current evidence on systemic immune dysregulation and organ-specific immunological mechanisms. A conceptual framework is proposed to facilitate a structured understanding of this complex syndrome and to guide future research toward targeted immunomodulatory strategies.},
}

Humans
*COVID-19/immunology/pathology/complications/virology
*SARS-CoV-2/immunology
Post-Acute COVID-19 Syndrome
Immunity, Innate
Adaptive Immunity
Organ Specificity
Autoimmunity

@article {pmid42043604,
year = {2026},
author = {Camara, B and Buonsenso, D},
title = {Response to letter: Methodological considerations for interpreting a scoping review of pediatric long COVID biomarkers.},
journal = {European journal of pediatrics},
volume = {185},
number = {5},
pages = {},
doi = {10.1007/s00431-026-06992-6},
pmid = {42043604},
issn = {1432-1076},
}

@article {pmid42043629,
year = {2026},
author = {Selvakumar, JP and Wyller, VBB},
title = {Methodological considerations for interpreting a scoping review of pediatric long COVID biomarkers.},
journal = {European journal of pediatrics},
volume = {185},
number = {5},
pages = {},
pmid = {42043629},
issn = {1432-1076},
}

@article {pmid42043742,
year = {2026},
author = {Tomaskovic, A and Weber, V and Ochmann, DT and Hillen, B and Neuberger, EWI and Brahmer, A and Lachtermann, E and Lieb, K and Simon, P},
title = {Cardiopulmonary Exercise Testing Reveals Functional Limitations and Work Disability in Severe Post-COVID-19 and ME/CFS Patients.},
journal = {Sports medicine - open},
volume = {12},
number = {1},
pages = {},
pmid = {42043742},
issn = {2199-1170},
abstract = {BACKGROUND: Patients severely affected by post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience long-term work incapacity, contributing to a growing economic burden. Organ-centered clinical diagnostics frequently fail to explain their work disability.

OBJECTIVES: We aimed to objectively assess physical work ability using cardiopulmonary exercise testing (CPET) in a cohort of long-standing and severely affected PCC patients. We hypothesized: (1) patients with ME/CFS exhibit lower peak oxygen uptake (VO₂peak [mL/min/kg]) and peak power output (PPO [W/kg]) than those without; (2) most patients demonstrate objective work disability, closely aligned with subjective perception of disability; (3) oxygen pulse (O2 pulse [mL/bpm]) is reduced in ME/CFS, independent of comorbidity.

METHODS: The study was conducted in the Department of Sports Medicine, Prevention and Rehabilitation at Johannes Gutenberg-University Mainz (Mainz, Germany). Between July 31, 2023, and March 31, 2025, a total of 92 PCC patients with suspected occupational disease underwent symptom-limited CPET and completed the Canadian Consensus Criteria, Bell Disability Scale (Bell-Score), and DePaul Symptom Questionnaire (Post-Exertional Malaise) Short Form (DSQ-PEM).

RESULTS: Nearly half of the patients (49%) met ME/CFS criteria and 79% screened positive on the DSQ-PEM. ME/CFS patients showed significantly lower VO₂peak (13.0 ± 3.1 vs. 15.4 ± 4.9, p = 0.012), PPO (0.9 ± 0.3 vs. 1.1 ± 0.5, p = 0.014), and O₂ pulse (7.7 ± 2.0 vs. 8.5 ± 1.9, p = 0.047) compared to those without ME/CFS. Overall, 66% of patients met objective thresholds for work disability (VO₂peak < 15 mL/min/kg or PPO < 1 W/kg). Forty-five patients (51%) had a Bell-Score ≤ 30 and 82% from those had VO₂peak < 15 and/or PPO < 1. VO₂peak and PPO significantly correlated with Bell-Score (r = 0.3, p = 0.005 and r = 0.3, p = 0.003) and were the lowest among patients on medical sick leave (13.3 ± 3.3 and 0.9 ± 0.3), compared to those in occupational reintegration (16.0 ± 3.9, p = 0.04 and 1.2 ± 0.5, p = 0.024) or currently working (18.0 ± 7.1, p = 0.036 and 1.2 ± 0.5, p = 0.015).

CONCLUSIONS: Severely affected PCC patients exhibit objective work disability, particularly those with ME/CFS. VO₂peak and PPO are associated with subjective disability and occupational status. Therefore, early integration of CPET into clinical and occupational evaluations can inform individualized therapy planning and return-to-work decisions. Trial registration DRKS, DRKS00032394. Registered 28 July 2023, https://drks.de/search/de/trial/DRKS00032394.},
}

@article {pmid42045916,
year = {2026},
author = {Li, S and Zhao, H and Zhang, M and Yuan, T and Li, X and Shen, Z and Qin, C and Li, Y and Pan, M},
title = {Long-term health outcomes in elderly COPD patients with long COVID: a 2-year prospective cohort study.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-026-03689-0},
pmid = {42045916},
issn = {1465-993X},
}

@article {pmid42035205,
year = {2026},
author = {Yuan, MQ and Pan, YF and Zhang, ZY and Wu, YX and Zhu, KD and Wang, ZR and Zhang, ZY and Xiong, JQ and Xu, Z and Huang, L and Wang, FS and Shi, L},
title = {Therapeutic potential of mesenchymal stromal cells in COVID-19: a meta-analysis of clinical trials conducted since the pandemic onset.},
journal = {Stem cell research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13287-026-05020-6},
pmid = {42035205},
issn = {1757-6512},
support = {No. 2022YFA1105604//National Key Research and Development Program of China/ ; },
abstract = {BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce immune dysregulation and multi-organ injury; mesenchymal stromal cell (MSC) therapy has shown promise in clinical trials for COVID-19 and may have broader applicability to pneumonia induced by respiratory viruses (e.g., the influenza virus). This meta-analysis synthesized the available comparative clinical evidence on the safety and efficacy of MSCs in patients with moderate to critical COVID-19 and examined the reported outcomes relevant to Long-COVID.

METHODS: We searched the PubMed, Embase, and CNKI databases for original, comparative studies in moderate, severe, or critical COVID-19 published up to September 2, 2024. Twenty-four eligible studies (13 RCTs and 11 non-randomized controlled trials; n = 1080) were included in the mortality meta-analysis. Patients were assigned to either the intervention group (MSC therapy plus standard care) or the control group (standard care with or without placebo). The primary efficacy outcome was all-cause mortality, while the primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included clinical recovery, hospitalization metrics, chest imaging, and inflammatory biomarkers. We performed a pooled meta-analysis on mortality with subgroup analyses (by disease severity, administration route, dosing frequency, and study design), assessment of publication bias (using funnel plots and Egger's test), and evaluation of the quality of evidence via the GRADE approach. AEs/SAEs were analyzed using meta-analysis and descriptive statistics, while other secondary outcomes were summarized descriptively.

RESULTS: MSC therapy significantly reduced all-cause mortality (MSC: 26.4% vs control: 31.9%; fixed-effect OR = 0.74, 95% CI 0.55-0.99), with low heterogeneity (I[2] = 2.8%, P =0.422[Q-test]) and no publication bias. The quality of evidence was moderate (according to the GRADE assessment). The subgroup analysis revealed a significant survival benefit in severe/critical patients (OR = 0.73, 95% CI 0.54-0.98) but not in studies that included moderate cases (OR = 0.91, 95% CI 0.23-3.65). No significant heterogeneity was found across study designs, administration routes, or dosing frequencies, which confirmed the robustness of the primary findings while indicating insufficient evidence to determine the optimal regimen. The secondary outcomes suggested improvements in clinical recovery, pulmonary function, and pro-/anti-inflammatory cytokine balance in patients that received MSC therapy. Limited studies with long-term follow-up indicated potential benefits for Long-COVID outcomes (e.g., fatigue, quality of life, residual CT abnormalities, and exercise tolerance). No significant differences were observed in AEs or SAEs post-MSC infusion, which suggested that MSC therapy was well tolerated.

CONCLUSION: This meta-analysis indicated that MSC therapy may reduce mortality in patients with severe or critical COVID-19, demonstrating a favorable safety profile and potential benefits for Long-COVID and other viral pneumonias. Further large-scale, rigorous RCTs and mechanistic studies are warranted to strengthen the evidence base and standardize MSC administration regimens (source, dosing, frequency, and intervals) for managing COVID-19, Long-COVID, and other viral pneumonias.},
}

@article {pmid39668387,
year = {2025},
author = {Savith, A and Meah, A and Murthy, RSS and Phal, NB},
title = {Long-term Health Implications of Coronavirus Disease 2019: A Prospective Study on Post-coronavirus Disease 2019 Symptoms.},
journal = {Annals of African medicine},
volume = {24},
number = {1},
pages = {167-172},
pmid = {39668387},
issn = {0975-5764},
mesh = {Humans ; *COVID-19/complications/epidemiology/physiopathology/diagnosis ; Prospective Studies ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Severity of Illness Index ; Aged ; Post-Acute COVID-19 Syndrome ; Hospitalization ; Prevalence ; Fatigue/epidemiology ; Dyspnea/epidemiology ; },
abstract = {CONTEXT: Patients recovering from coronavirus disease 2019 (COVID-19) infection continue to have some persistent symptoms or develop new symptoms, resulting in impairment of everyday activities beyond the initial acute period. The current study was undertaken to understand the long term health implications of covid 19 and to analyse the correlation of post covid symptoms with the severity of infection and inflammatory markers at the time of hospitalisation.

AIMS: (1) To estimate the prevalence of post covid symptoms at the end of 1 month,3 months and 12 months after discharge, (2) To correlate post covid symptoms with the severity of infection and inflammatory markers at the time of hospitalisation.

SETTINGS AND DESIGN: The study design was a cross-sectional study.

SUBJECTS AND METHODS: A prospective observational study was done on 150 COVID-19 reverse transcription-polymerase chain reaction-positive patients aged 18 years and above recovering from acute infection discharged from Vydehi Institute of Medical Sciences and Research Centre. All the patients were followed up for 1 year, during which telephonic interviews were conducted, and a systematic enquiry was made regarding post-COVID-19 symptoms.

STATISTICAL ANALYSIS USED: Data were entered in MS Excel and analyzed in SPSS V25. Descriptive statistics are represented with percentages, mean with standard deviation, or median with interquartile range depending on the nature of the data. The Kolmogorov-Smirnov test was applied to find normality. The Chi-square test, Independent t -test, or Mann-Whitney U -test were calculated depending on normality; P < 0.05 was considered statistically significant.

RESULTS: A total of 150 COVID-19-positive patients discharged from the hospital were included in the study. Sixty-seven percent of patients had symptoms at 1 month, 39% at 3 months, and 31% of patients persisted to have symptoms at 1 year. The most common symptoms at 1 year were fatigue (5%), breathlessness (5%), and insomnia (5%). No statistically significant correlation was found with the severity of infection, inflammatory markers, and other variables.

CONCLUSIONS: Approximately one-third of patients who recover from acute COVID-19 infection may continue to have post-COVID-19 symptoms at 1 year after infection. Fatigue is the most common post-COVID-19 symptom. Post-COVID-19 symptoms can affect COVID-19 survivors regardless of the severity of the infection.},
}

Humans
*COVID-19/complications/epidemiology/physiopathology/diagnosis
Prospective Studies
Male
Female
Middle Aged
Cross-Sectional Studies
Adult
SARS-CoV-2
Severity of Illness Index
Aged
Post-Acute COVID-19 Syndrome
Hospitalization
Prevalence
Fatigue/epidemiology
Dyspnea/epidemiology

@article {pmid42026739,
year = {2026},
author = {Thomas, C and Ashton, RE and Owen, R and McNeil-Angopa, E and Carr, J and Bewick, T and Faghy, MA},
title = {Impaired peripheral oxygen delivery during submaximal exercise in adults with long COVID.},
journal = {Physiological reports},
volume = {14},
number = {8},
pages = {e70873},
doi = {10.14814/phy2.70873},
pmid = {42026739},
issn = {2051-817X},
support = {IN-UK-983-6080//Gilead Sciences (Gilead)/ ; },
mesh = {Humans ; *COVID-19/physiopathology/metabolism/complications ; Male ; Female ; Middle Aged ; *Muscle, Skeletal/metabolism/physiopathology ; *Exercise/physiology ; Exercise Test ; Adult ; *Oxygen Consumption ; *Oxygen/metabolism ; Spectroscopy, Near-Infrared ; SARS-CoV-2 ; },
abstract = {Long COVID (LC) is a multisystem condition that is linked to distinct pathologies including viral persistence, immunological dysfunction, endothelial damage, and mitochondrial dysfunction. To date, limited research has assessed peripheral tissue hypoxia to better understand LC symptom exacerbation. Forty-six people with LC and 10 controls (CON) completed two submaximal cardiopulmonary exercise tests (CPETs), separated by 24-h. Near-infrared spectroscopy (NIRS)-derived signals from the left gastrocnemius muscle were continuously monitored before, during, and after 2-day incremental CPET. CPET outcomes demonstrated impaired physical function on day 2 compared with day 1 for the LC cohort at rest and VT1. LC tissue saturation index (TSI%) remained elevated above rest for a shorter duration of exercise compared to CON on day 1 (2nd minute vs. 5th minute). On day 2, this response worsened for LC (Rest vs. 1st exercise minute: 63 ± 5% vs. 65 ± 5%; p < 0.05); meanwhile, CON exhibited sustained TSI% elevation throughout exercise above rest (Rest vs. 12th exercise minute: 62 ± 5% vs. 67 ± 4%; p < 0.05). LC TSI% remained elevated above rest for a shorter duration of exercise compared to CON, worsening for LC on day 2. LC showed rapid normalization of TSI%, suggesting impaired muscle oxygenation and recovery during repeated exercise.},
}

Humans
*COVID-19/physiopathology/metabolism/complications
Male
Female
Middle Aged
*Muscle, Skeletal/metabolism/physiopathology
*Exercise/physiology
Exercise Test
Adult
*Oxygen Consumption
*Oxygen/metabolism
Spectroscopy, Near-Infrared
SARS-CoV-2

@article {pmid42028736,
year = {2026},
author = {Samet, M and Aghaei-Meybodi, FA and Hosseini, S and Meidany, A and Fateh, A},
title = {Lung autopsy findings in 44 COVID-19 deceased patients:pathological and radiological insights.},
journal = {Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace},
volume = {},
number = {},
pages = {},
doi = {10.4081/monaldi.2026.3412},
pmid = {42028736},
issn = {2532-5264},
abstract = {This study presents a detailed histopathological analysis of lung tissue from 44 deceased COVID19 patients, aiming to elucidate the mechanisms driving severe disease progression. Postmortem biopsies were systematically examined, revealing diffuse alveolar damage in 95.5% of cases, predominantly in the acute/exudative phase. Characteristic features included extensive hyaline membrane formation, alveolar septal thickening, fibrin deposition, and red blood cell extravasation. Notably, advanced fibrosis, indicative of ongoing tissue remodeling, was observed in 86.4% of cases, highlighting the chronic pathological impact of the disease. Patient demographics showed a predominance of older males with comorbidities such as hypertension and diabetes, aligning with known high-risk profiles. The methodology involved meticulous autopsy procedures and standardized histopathological assessments to ensure the reliability of findings. This study provides key insight into histological changes in the lungs of COVID-19 patients, helping to clarify the disease's progression. It provides valuable insights that may contribute to a better understanding of long COVID and the potential long-term pulmonary complications in these patients. These findings may ultimately support improved management approaches and therapeutic strategies for COVID-19 care.},
}

@article {pmid42028925,
year = {2026},
author = {Silva, LI and Gonzalez-Zambrano, CM and Ferreira, VCMP and Corrêa, FC and Dias-Melicio, LA},
title = {MicroRNAs in Acute COVID-19 and Long COVID: Dysregulation, Pathogenic Roles, and Clinical Implications.},
journal = {Journal of immunology research},
volume = {2026},
number = {1},
pages = {e5862241},
doi = {10.1155/jimr/5862241},
pmid = {42028925},
issn = {2314-7156},
support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; },
mesh = {Humans ; *COVID-19/genetics/immunology/virology/pathology ; *MicroRNAs/genetics ; *SARS-CoV-2/physiology/immunology ; Post-Acute COVID-19 Syndrome ; Extracellular Vesicles ; Gene Expression Regulation ; Biomarkers ; Inflammation ; },
abstract = {MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression with central roles in immune responses, inflammation, and viral pathogenesis. Increasing evidence indicates that severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection induces marked dysregulation of host and viral miRNAs (v-miRNAs), contributing to disease severity during acute COVID-19 and to the persistent manifestations observed in long COVID (LC). This narrative review critically synthesizes current evidence on miRNA dysregulation across the acute and post-acute phases of COVID-19, highlighting their pathogenic roles, clinical relevance, and existing knowledge gaps. During acute infection, altered miRNA profiles-including those associated with immune activation, endothelial dysfunction, and immunothrombosis-reflect both host responses and viral strategies of immune modulation, including miRNAs carried by extracellular vesicles (EVs) and SARS-CoV-2-derived v-miRNAs. In LC, emerging data suggest that persistent miRNA alterations are associated with unresolved inflammation, pulmonary dysfunction, neurological symptoms, and vascular injury, although available studies remain limited and heterogeneous. Overall, miRNAs represent promising biomarkers and potential therapeutic targets in COVID-19; however, robust longitudinal and mechanistic studies are urgently needed to clarify their causal roles and translational utility in post-acute disease.},
}

Humans
*COVID-19/genetics/immunology/virology/pathology
*MicroRNAs/genetics
*SARS-CoV-2/physiology/immunology
Post-Acute COVID-19 Syndrome
Extracellular Vesicles
Gene Expression Regulation
Biomarkers
Inflammation

@article {pmid42029517,
year = {2026},
author = {Couto, NMS and Bernal, JVM and Facioli, TP and Dos Santos, D and de Souza, HCD},
title = {The Severity of COVID-19 Is Associated with Greater Impairment of Cardiac Autonomic Modulation-Physical Training as a Countermeasure.},
journal = {Journal of functional morphology and kinesiology},
volume = {11},
number = {2},
pages = {},
doi = {10.3390/jfmk11020149},
pmid = {42029517},
issn = {2411-5142},
support = {2023/17422-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
abstract = {Background: COVID-19 has been associated with persistent impairments in autonomic modulation of heart rate variability (HRV). However, whether disease severity during the acute phase influences the magnitude of these impairments remains insufficiently explored. In turn, aerobic physical training (APT) has been proposed as a countermeasure to autonomic dysfunction of HRV in different conditions, although its effects in individuals with COVID-19 are not yet well established. To address these gaps, this study investigated the consequences of COVID-19 on autonomic modulation of HRV according to disease severity and evaluated the effects of APT on this parameter. Methods: One hundred and sixteen individuals (58 men and 58 women) aged between 30 and 55 years were included, allocated into three groups according to the severity of the disease in the acute phase: Mild group (n = 38, mean age: 48 ± 7 years); Moderate group (n = 52, mean age: 43 ± 5 years); and Severe group (n = 26, mean age: 45 ± 6 years). All groups had anthropometric and hemodynamic parameters evaluated before and after the 16-week APT period, as well as parameters of autonomic modulation of HRV analyzed using linear (time and frequency domain) and non-linear (symbolic analysis) methods obtained from R-R interval (RRi) recordings in the supine position for 30 min. Results: Initially, all groups presented similar anthropometric and hemodynamic values. In contrast, the Moderate and Severe groups presented lower values for standard deviation of normal RRi (SDNN; Moderate: 38 ± 14 ms; Severe: 33 ± 12 ms vs. Mild: 55 ± 28 ms; p < 0.001), root mean square difference between adjacent normal RRi (RMSSD; Moderate: 28 ± 13 ms; Severe: 22 ± 7 ms vs. Mild: 47 ± 38 ms; p < 0.001), total variance (Moderate: 203 ± 127 ms[2]; Severe: 303 ± 157 ms[2] vs. Mild: 526 ± 347 ms[2]; p < 0.001), and high-frequency (HF) oscillations in absolute units (Moderate: 259 ± 270 ms[2]; Severe: 153 ± 74 ms[2] vs. Mild: 438 ± 421 ms[2]; p < 0.001), both compared to the Mild group. In turn, the Severe group, when compared to the other groups, also presented lower HF oscillations (Severe: 29 ± 12 nu vs. Mild: 44 ± 17 nu and Moderate: 42 ± 17 nu; p < 0.001) and higher low-frequency (LF) oscillations (Severe: 71 ± 12 nu vs. Mild: 60 ± 17 nu and Moderate: 58 ± 17 nu; p < 0.001), but in normalized units. After the 16-week APT, all groups showed increases in HF oscillations (Mild: -206 ms[2] and -19.12 nu; Moderate: -236 ms[2] and -26.7 nu; Severe: -211 ms[2] and -31.0 nu; p < 0.001) and reductions in LF oscillations (Mild: 198 ms[2] and 19.01 nu; Moderate: 98 ms[2] and 26.7 nu; Severe: 218 ms[2] and 31.1 nu; p < 0.001), both in absolute and normalized units. In this case, there were no further differences in LF and HF oscillations between the groups. Conclusions: Individuals who had COVID-19 and developed moderate to severe cases showed greater impairments in the autonomic modulation of HRV, characterized by increased sympathetic autonomic modulation and reduced vagal modulation. In turn, APT as a countermeasure appears to increase vagal autonomic modulation and reduce sympathetic autonomic modulation of HRV, regardless of the previous severity of COVID-19.},
}

@article {pmid42021271,
year = {2026},
author = {Sommen, SL and Segtnan, S and Selvakumar, J and Havdal, LB and Stiansen-Sonerud, T and Gjerstad, J and Mjaaland, S and Nygaard, UC and Wyller, VBB and Mukherjee, R and Berven, LL},
title = {Long COVID: Deep single-cell immunophenotyping and machine learning reveal a general signature for fatigue.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08149-3},
pmid = {42021271},
issn = {1479-5876},
}

@article {pmid42022303,
year = {2025},
author = {Tabarsi, P and Mohamadnia, A and Shahabinejad, P and Haseli, S and Askari, E and Bahrami, N and Shafaghi, S and Hajimoradi, M},
title = {Long COVID in Patients with Multiple Sclerosis Treated with Rituximab: A Report of Two Cases.},
journal = {Tanaffos},
volume = {24},
number = {1},
pages = {106-110},
pmid = {42022303},
issn = {1735-0344},
abstract = {COVID-19 symptoms may persist for more than 12 weeks in some infected patients, a condition described as long COVID-19 in these cases. These patients have symptoms attributed to impairment of multiple organs. Scientists have discovered the lengthy COVID-19 etiology, risk factors, and treatments. It has been observed that immunosuppression may prolong COVID-19 symptoms. Patients with multiple sclerosis (pwMS) are generally treated with disease-modifying treatments, which suppress the immune system and predispose patients to infections like COVID-19. Also, these drugs may increase not only the morbidity and mortality of infection but also the risk of developing long COVID-19 in these patients. We have described two cases of multiple sclerosis patients who were diagnosed with long COVID-19. Both patients were under treatment with rituximab, so we discussed treatment choices and strategies for pwMS patients under rituximab who had symptoms of long COVID. Our data would further add to the information on managing long COVID-19 in pwMS under treatment with rituximab.},
}

@article {pmid42022621,
year = {2026},
author = {Obeagu, EI},
title = {Taming the Cytokine Storm: Therapeutic Strategies for Post-Acute Sequelae of SARS-CoV-2 Infection.},
journal = {Health science reports},
volume = {9},
number = {3},
pages = {e72174},
pmid = {42022621},
issn = {2398-8835},
abstract = {BACKGROUND AND AIM: Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as long COVID, has emerged as a significant global health concern, marked by persistent symptoms and chronic inflammation following recovery from acute COVID-19. A central driver of PASC pathogenesis is the sustained cytokine storm-an exaggerated and prolonged pro-inflammatory response that leads to ongoing tissue injury and multisystem dysfunction. This review aims to synthesize current knowledge on cytokine dysregulation in PASC and evaluate emerging therapeutic strategies targeting these immunopathological mechanisms.

METHODS: A narrative review methodology was employed, drawing from recent peer-reviewed publications, clinical trial databases, and immunological studies published between 2020 and 2025. Articles focusing on cytokine profiles in PASC, immune reprogramming, and immunomodulatory therapies were included. Mechanistic studies, biomarker research, and translational trials involving corticosteroids, cytokine inhibitors, Janus kinase (JAK) inhibitors, and novel biologics were critically analyzed.

RESULTS: The literature reveals that elevated levels of IL-6, IL-1β, TNF-α, and IFN-γ persist in a subset of PASC patients, contributing to chronic systemic and organ-specific inflammation. Emerging therapies-including IL-6 and IL-1 receptor antagonists, JAK inhibitors, and CNS-penetrant anti-inflammatory agents-demonstrate promise in modulating cytokine storms and improving clinical outcomes. Recent insights into cytokine profiling, trained immunity, and neuroimmune crosstalk suggest potential for precision-based interventions tailored to distinct inflammatory phenotypes in PASC.

CONCLUSION: Persistent cytokine dysregulation underlies the pathophysiology of PASC and offers actionable targets for therapeutic intervention. Immunomodulatory strategies, when guided by biomarker profiling and systems biology approaches, hold promise for mitigating long-term complications of COVID-19. Future research should prioritize personalized treatment algorithms to address the heterogeneity of PASC and enhance patient recovery.},
}

@article {pmid42026280,
year = {2026},
author = {Stanley, HB and Bensafi, M},
title = {The characteristics of chemosensory losses in the symptomatology of long-COVID.},
journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery},
volume = {},
number = {},
pages = {},
pmid = {42026280},
issn = {1434-4726},
support = {964529//Horizon 2020 Framework Programme/ ; Human Chemosensation IRP project//CNRS/ ; },
}

@article {pmid42002663,
year = {2026},
author = {Stervbo, U and Anft, M and Paniskaki, K and Blazquez-Navarro, A and Doevelaar, A and Skrzypczyk, S and Kohut, E and Kurek, J and Wehler, P and Kaliszczyk, S and Rosiewicz, K and Seibert, FS and Hölzer, B and Thieme, CJ and Roch, T and Konik, MJ and Berger, MM and Brenner, T and Kölsch, U and Adamzik, M and Schmueck-Henneresse, M and Scheibenbogen, C and Dolff, S and Dittmer, U and Witzke, O and Westhoff, TH and Babel, N},
title = {Acute COVID-19 is associated with altered CD8 T-cells indicative of impaired ability to control Epstein-Barr virus reactivation.},
journal = {Medical microbiology and immunology},
volume = {215},
number = {1},
pages = {},
pmid = {42002663},
issn = {1432-1831},
abstract = {UNLABELLED: Increasing evidence suggests that reactivation of latent EBV in patients with COVID-19 may be linked to the development of post-acute sequelae of COVID-19, colloquially known as Long COVID. However, the reason for this co-occurrence of primary infection and reactivation of latent viruses remains elusive. During the first wave of COVID-19, we assessed all major immune cell populations by flow cytometry in a cohort of 61 patients with moderate to critical COVID-19 at the time of hospitalization. Additional blood samples from these patients were biobanked for later analysis. Using these biobanked samples, we evaluated the co-occurrence of CMV, EBV, as well as HHV-6A and -6B by qPCR. EBV was found to be reactivated not only in patients with critical or severe COVID-19 (24/33 patients; 72.72%), but also in patients with moderate COVID-19 disease (19/28; 67.86%) at the time of hospital admission. In contrast, HHV-6A was not detected among any patients, whereas CMV and HHV-6B only occurred in low frewuencies (7.1–12.1% and 10.7–15.2%, respectively). In COVID-19 patients with EBV reactivation, the degree of expression of the T-cell co-stimulatory CD28 and co-expression of CD28 and the integrin CD11a was diminished on CD8 T-cells. In contrast, the frequency of CD8 T-cells expressing the proliferative exhaustion marker CD57 increased. Collectively, these data point to an altered activation phenotype of circulating CD8 T cells and that higher replicative senescence is associated with EBV reactivation. The data presented here suggests an alteration in the CD8 T-cell compartment with impaired ability to control the EBV reactivation in COVID patients.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00430-026-00873-3.},
}

@article {pmid42015188,
year = {2026},
author = {Sardell, JM and Das, S and Pearson, M and Kolobkov, D and Malinowski, AR and Fullwood, LM and Sanna, M and Baxter, H and McLellan, K and Natt, M and Lamirel, D and Chowdhury, S and Strivens, MA and Gardner, S},
title = {Identification of novel reproducible combinatorial genetic risk factors for myalgic encephalomyelitis in the DecodeME patient cohort and commonalities with long COVID.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08167-1},
pmid = {42015188},
issn = {1479-5876},
support = {10083274//Innovate UK/ ; },
}

@article {pmid42016647,
year = {2026},
author = {Wetmore, E and Grach, S and Boes, C and Lanzino, G and Kissoon, N},
title = {Long COVID Syndrome and Associated New Daily Persistent Headache (NDPH) Presenting With Crossed Clonus Response.},
journal = {Clinical case reports},
volume = {14},
number = {3},
pages = {e72386},
pmid = {42016647},
issn = {2050-0904},
abstract = {Evaluating patients following a COVID-19 infection with multiple chronic, progressive symptoms can be challenging, but easy to navigate by using the temporal profile obtained from the clinical history, findings from the neurological exam, and screening for red flag symptoms.},
}

@article {pmid42017188,
year = {2026},
author = {Alvarez-Pedrerol, M and Polo-Alonso, S and Ramos, R and Martí-Lluch, R and Pinsach-Abuin, ML and Dégano, IR and Elosua, R and Subirana, I and Hernáez, Á and Selga, E and Puigdecanet, E and Pruneda-Paz, J and Solà-Richarte, C and Puigmulé, M and Pérez, A and Nogués, X and Masclans, JR and Güerri-Fernández, R and Cubero-Gallego, H and Tizon-Marcos, H and Vaquerizo, B and Brugada, R and Camps-Vilaró, A and Marrugat, J},
title = {Sex Differences in Long COVID Prevalence Over One year After the Acute Phase, and Related Risk Factors. The GINA-COVID Cohort Study.},
journal = {International journal of women's health},
volume = {18},
number = {},
pages = {538491},
pmid = {42017188},
issn = {1179-1411},
abstract = {BACKGROUND: This 1-year cohort study aimed to track long COVID prevalence, identify associated risk factors, and assess its association with hospitalization.

METHODS: The GINA-COVID cohort study included 2698 COVID-19 patients from Spain, who reported persistent symptoms spontaneously mentioned in an open questionnaire one year after infection. We recorded symptom onset, duration, and recovery rates at 12 months. Hospitalization data were collected from the Catalan Health System. We performed descriptive statistics and logistic regression models stratified by sex to identify factors associated with long COVID, using multiple imputation for missing values and model selection via stepwise regression based on the Akaike Information Criterion.

RESULTS: Significant sex differences appeared, with females showing a two-fold higher risk of developing long COVID compared to males (OR=1.95; 95% CI, 1.68-2.29). Females reported higher prevalence and a greater number of persistent symptoms, with fatigue being the most common in both sexes (36% in females, 26% in males at 3 months). The recovery rate at 12 months was lower in females (23% vs. 34%, p<0.001). Hypertension emerged as the most significant protective factor for long COVID in females (OR=0.64; 95% CI, 0.48-0.84), whereas COVID-19 severity was the most influential risk factor in males (OR=2.34; 95% CI, 1.79-3.08). Despite these differences, the trajectory of persistent symptoms over time was similar between the sexes. Importantly, long COVID did not increase hospital admissions.

CONCLUSION: Findings underscore the importance of sex-specific approaches in managing long COVID and suggest further investigation into hypertension's protective role in females and disease severity's impact in males.},
}

@article {pmid42017426,
year = {2026},
author = {Krzyzanowski, MC and Pan, H and Glaze, I and Hwang, S and Williams, D and Engle, M and Waterfield, J and Ives, C and Armson, S and Huggins, W and Hamilton, CM},
title = {The PhenX Toolkit: Long COVID Collection of Standard Protocols.},
journal = {Current protocols},
volume = {6},
number = {4},
pages = {e70317},
doi = {10.1002/cpz1.70317},
pmid = {42017426},
issn = {2691-1299},
support = {/HG/NHGRI NIH HHS/United States ; (U41HG007050)//Genomic Research/ ; (U24HG012556)//Biomedical Knowledgebase/ ; /CD/ODCDC CDC HHS/United States ; /HL/NHLBI NIH HHS/United States ; /NS/NINDS NIH HHS/United States ; /MD/NIMHD NIH HHS/United States ; /CA/NCI NIH HHS/United States ; /DA/NIDA NIH HHS/United States ; //Office of Behavioral and Social Sciences Research/ ; /ES/NIEHS NIH HHS/United States ; //Disaster Research Response (DR2)/ ; },
mesh = {Humans ; *COVID-19/complications/epidemiology ; SARS-CoV-2 ; *Data Collection/methods ; Crowdsourcing/methods ; },
abstract = {Because of the urgent need to better understand the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission mechanism and clinical outcomes resulting from infection, health organizations and research institutes developed data collection instruments to assess coronavirus disease 2019 (COVID-19) symptoms, treatments, and associated impacts on behaviors and risks, treatment and outcomes, information available, psychosocial and mental health, and socioeconomic effects across demographic groups. The PhenX team developed the COVID-19 Protocol Library to share data collection instruments, methods, and protocols in use by investigators and to reduce proliferation of similar protocols. The Office of Behavioral and Social Sciences Research and the National Human Genome Research Institute sponsored the effort, in collaboration with the NIH Disaster Research Response Program. As the COVID-19 library was being established, crowdsourcing was used to identify key topics related to the pandemic, which formed the basis of the COVID-19 Research Collection, and was released in the PhenX Toolkit. Long COVID continues to have an impact on human health. Long COVID is a chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months, encompassing a variety of symptoms or conditions that may improve, worsen, or be ongoing. Not surprisingly, submissions to the COVID-19 library began to address Long COVID symptoms. After discussions with its Steering Committee, the PhenX team established a collection of Long COVID measurement protocols. Also, there was significant interest in assessing the amount of overlap among all instruments submitted to the COVID-19 library. The intent was to develop a tool that could identify potential for cross-study analyses. The COVID-19 Variable Compare Tool (VCT) integrates all COVID-19 Research Collection protocols and a prioritized subset of instruments from the COVID-19 library. The Long COVID Specialty Collection and the VCT support investigators' needs to combine and analyze data related to COVID-19 prospectively and retrospectively by identifying compatibility with other studies. © 2026 RTI International. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Exploring Long COVID through PhenX Toolkit Specialty Collections and the Variable Compare Tool.},
}

Humans
*COVID-19/complications/epidemiology
SARS-CoV-2
*Data Collection/methods
Crowdsourcing/methods

@article {pmid42017829,
year = {2026},
author = {Sun, H and Dang, R and Li, P and Xiao, W and Scott-Sutherland, J and Sassower, KC and Westover, MB and Felsenstein, D and Thomas, RJ and Haack, M and Mullington, JM},
title = {Facility-Measured Sleep Electroencephalographic Microstructures in Long COVID.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsag090},
pmid = {42017829},
issn = {1550-9109},
abstract = {STUDY OBJECTIVES: Sleep electroencephalographic (EEG) microstructures are related to brain functions, providing a window into the unrefreshing, non-restorative sleep and daytime fatigue symptoms in long COVID (LC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We aim to characterize sleep EEG microstructural differences in individuals with LC and age-sex-matched healthy controls (HC), and also ME/CFS, using overnight in-lab facility-measured polysomnography (PSG).

METHODS: 28 LC and 28 HC participants came from a single-center research study. 19 ME/CFS participants came from a single clinical center. Sleep EEG was processed to extract spectral band powers, spindles, slow oscillations (SO, 0.5-1 Hz), spindle-SO coupling, brain age index (BAI), alpha-delta patterns, and infraslow oscillation relative band power (ISO, 0.005-0.03 Hz).

RESULTS: Compared to HC, LC had higher SO power during wake before sleep and REM sleep. In N2 and N3, LC showed a faster within-spindle frequency drop (chirp) and shorter SO peak duration in the frontal region. LC showed widespread, early spindle-SO coupling phase at SO trough for both fast and slow spindles, with early fast spindle-SO coupling associated with worse sleep quality. ME/CFS shared some differences with LC but had higher SO-uncoupled slow spindle densities in frontal and central regions, more alpha-delta patterns in the first half of the night, and widespread elevated ISO power in the slow sigma band (11-13 Hz).

CONCLUSIONS: These findings suggest that LC and ME/CFS are associated with plausibly pathological sleep EEG microstructure changes, illuminating the pathobiology of post-infectious processes on brain activity.CLINICAL TRIAL INFORMATIONTrial 1: Sleep and Inflammatory Resolution Pathway, https://clinicaltrials.gov/study/NCT03377543, NCT03377543.Trial 2: Pain in Long COVID-19: the Role of Sleep, https://clinicaltrials.gov/study/NCT05606211, NCT05606211.},
}

@article {pmid42018978,
year = {2026},
author = {Gesell, D and Lienesch, P and Shi, Y and Strobl, R and Tauscher, M and Gerlach, R and Grill, E and Koller, D},
title = {Care Pathways and Patient Experiences Among Patients With Post COVID-19 Condition: Study Protocol for a Mixed-Methods Study in Germany.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e91976},
doi = {10.2196/91976},
pmid = {42018978},
issn = {1929-0748},
mesh = {Humans ; Germany/epidemiology ; *COVID-19/therapy/complications/epidemiology ; Retrospective Studies ; SARS-CoV-2 ; Qualitative Research ; *Patient Acceptance of Health Care/statistics & numerical data ; *Critical Pathways ; Research Design ; Female ; Male ; Focus Groups ; Post-Acute COVID-19 Syndrome ; Pandemics ; },
abstract = {BACKGROUND: The COVID-19 pandemic has a lasting impact on health care utilization, as both the acute infection and post COVID condition (PCC) can lead to increased demand for medical services due to ongoing symptoms.

OBJECTIVE: The aim of this study is to systematically examine health care utilization among individuals after acute SARS-CoV-2 infection in Bavaria, Germany, with a particular focus on PCC. The study combines claims data analysis with qualitative interviews to improve the understanding of objective care pathways and patients' subjective experiences within the health care system.

METHODS: The research project 'SOLongCOVID' employs a mixed-methods design consisting of two subprojects: (1) a retrospective cohort study using claims data from the Bavarian Association of Statutory Health Insurance Physicians (KVB) to analyze care pathways through state sequence analysis, (2) a qualitative study based on semistructured interviews and focus groups with patients with PCC concerning their subjective care experiences. A synthesis process involving a focus group discussion will combine the information from the two subprojects, providing a comprehensive understanding of the care processes of patients with PCC.

RESULTS: The study was funded by the German Federal Joint Committee Innovation Fund in October 2024. Statutory health insurance claims data cover the period from 2019 to 2022, and qualitative interview data collection is planned from May 2025 to August 2026. As of manuscript submission, study preparation and ethics approvals have been completed, and 14 participants have been recruited for the qualitative interviews. Study findings are anticipated to be published from July 2026 to August 2027.

CONCLUSIONS: The results are expected to enhance the understanding of existing barriers and challenges and to support evidence-based recommendations for improving care pathways for patients with specific care needs.},
}

Humans
Germany/epidemiology
*COVID-19/therapy/complications/epidemiology
Retrospective Studies
SARS-CoV-2
Qualitative Research
*Patient Acceptance of Health Care/statistics & numerical data
*Critical Pathways
Research Design
Female
Male
Focus Groups
Post-Acute COVID-19 Syndrome
Pandemics

@article {pmid42019647,
year = {2026},
author = {Nieuwland, JM and Scaramuzza, A and Bugiani, M and van de Berg, WDJ and Middeldorp, J},
title = {Human brain matters: Navigating the neuropathology of COVID-19.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70101},
doi = {10.1111/bpa.70101},
pmid = {42019647},
issn = {1750-3639},
support = {//European research project NEUROCOV, funded by Horizon Europe (EU)/ ; },
abstract = {Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths worldwide. Although the incidence of severe acute cases has declined, the prevalence of long COVID, also known as post-acute sequelae of COVID-19 (PASC), is rising. The pathological mechanisms underlying severe COVID-19, along with the relationship to neurological disorders and potential risk for neurodegeneration, remain poorly understood. The aim of this narrative review is to summarize neuropathological features described in postmortem human COVID-19 brains (n = 352). Furthermore, analysis of biofluids and neuroimaging from PASC patients underline long-term changes in the proteome and CNS response following the infection. Postmortem brain studies from severe COVID-19 patients highlight disruption of the fluid-brain barriers and vascular dysregulation defined by endothelial inflammation and disruption, hemorrhages, and hypoxic-ischemic damage. Neuroinflammation, including astrogliosis, microglia nodules and infiltration of adaptive immune cells, has been reported in the olfactory bulb, medulla oblongata, midbrain and cerebellum. Neuronal damage was demonstrated in the hippocampus, midbrain and cerebellum in severe COVID-19 and protein aggregation was observed in the midbrain and entorhinal cortex. Neuropathological burden and elevated blood and/or cerebrospinal fluid (CSF) levels of proinflammatory cytokines (e.g. IL-6) and neuro-axonal proteins (e.g. NfL) correlated with severity of anosmia, memory deficits, and cerebellar ataxia. Elderly patients and/or patients with underlying neurological diseases were more susceptible and had worsened symptoms. Potential disease mechanisms underlying neurological symptoms observed in severe COVID-19 are vascular and fluid-brain barrier abnormalities, chronic neuroinflammation, persistent axonal damage and protein aggregation. In PASC patients, an altered biofluid proteome with increased neuronal proteins and pro-inflammatory cytokines was observed. The pathological burden in affected brain regions may contribute to manifestations such as anosmia, memory deficits, and cerebellar ataxia.},
}

@article {pmid42020802,
year = {2026},
author = {Steifman, CB and Alvarez-Carcamo, B and Verma, S and McCarthy, R and Guthrie, LB and Gill, KK and Swank, Z and Walt, DR and Grabowski, EF and Fasano, A and VanElzakker, MB and Irimia, D and Yonker, LM},
title = {Endovascular profiles linked to neutrophil activation in children and young adults with long COVID.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {42020802},
issn = {1530-0447},
abstract = {BACKGROUND: Endovascular symptoms are among the most debilitating long COVID symptoms; however, underlying mechanisms are unclear. Children and young adults with long COVID, an understudied population, offer key insight into long COVID pathology.

METHODS: Eighty-four children and young adults ≤25 years from the U.S. and Canada were enrolled; 61 with long COVID and 23 healthy pediatric controls. We assessed symptom burden, quantified fibrin amyloid microclots, endovascular cytokines, cell-free DNA, and conducted in vitro assays to assess Spike-related neutrophil-mediated endothelial cell injury.

RESULTS: Cardiovascular symptoms were prevalent among participants with long COVID. Microclot burden was increased (p = 0.0003), as were markers of angiogenesis and endothelial remodeling, including FGF-2, which correlated with microclots (p = 0.04). Cytokines involved in leukocyte trafficking (sVCAM-1, L-selectin, α-2-macroglobulin) were reduced while cell-free DNA, a marker of intravascular neutrophil extracellular trap (NET) formation, was increased (p = 0.003) and positively correlated with microclot component serum amyloid A (p = 0.004). Co-culture assays revealed that NETosis, triggered by Spike immune complexes, contributes to endothelial injury in long COVID.

CONCLUSIONS: Children and young adults with long COVID with cardiovascular symptoms display increased microclots, endothelial injury, and neutrophil inflammation, which warrant further evaluation and suggest intravascular NETosis as a key driver of endovascular pathology in long COVID.

IMPACT: Children and young adults with long COVID display elevated endothelial biomarkers, underscoring disease-related rather than age-related endovascular profiles following SARS-CoV-2 infection. Children and young adults with long COVID exhibit increased microclot burden in blood. Neutrophil activation may contribute to ongoing endovascular injury in long COVID. A combination of microclots, neutrophil markers, and endothelial cytokines could serve as biomarkers for Long COVID.},
}

@article {pmid42008509,
year = {2026},
author = {Ortega-Martin, E and Alvarez-Galvez, J},
title = {Understanding quality-of-life patterns in long COVID: How Symptoms and socioeconomic conditions shape patient wellbeing.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0347743},
doi = {10.1371/journal.pone.0347743},
pmid = {42008509},
issn = {1932-6203},
mesh = {Humans ; *Quality of Life ; Male ; Female ; Middle Aged ; *COVID-19/epidemiology/psychology/pathology ; Cross-Sectional Studies ; Adult ; Aged ; Spain/epidemiology ; Socioeconomic Factors ; SARS-CoV-2/isolation & purification ; Surveys and Questionnaires ; Fatigue ; Social Support ; },
abstract = {OBJECTIVE: To characterize the heterogeneity of Long COVID (LC) by identifying distinct patient profiles based on symptoms and quality of life (QoL), and to examine the sociodemographic and clinical predictors associated with these profiles.

STUDY DESIGN: A cross-sectional observational study was conducted.

METHODS: We recruited 363 patients with LC in Spain via an online survey. Symptom patterns were identified through latent class analysis of 15 binary symptoms. QoL was assessed with the patient-derived LC-6D-QoL across six dimensions, and cluster analysis defined QoL subgroups. Logistic regression was applied to examine clinical and sociodemographic predictors of QoL profiles.

RESULTS: Two symptom profiles emerged: a low-burden profile, dominated by fatigue and cognitive problems, and a high-burden profile with multisystem involvement. QoL clustered into three profiles-high, middle, and low QoL-with more than half of participants in the low QoL group. Symptom burden and employment status were the strongest predictors of poor QoL, whereas age, sex, education, and income showed limited associations. Social support was more frequently reported among participants with low QoL.

CONCLUSIONS: LC is characterized by distinct clinical and QoL profiles, with strong interactions between multisystem symptom burden and social determinants. Identifying patients at greatest risk of poor QoL can inform stratified interventions and integrated policies that combine medical care, psychosocial support, and workplace reintegration.},
}

Humans
*Quality of Life
Male
Female
Middle Aged
*COVID-19/epidemiology/psychology/pathology
Cross-Sectional Studies
Adult
Aged
Spain/epidemiology
Socioeconomic Factors
SARS-CoV-2/isolation & purification
Surveys and Questionnaires
Fatigue
Social Support

@article {pmid42010131,
year = {2026},
author = {Floridia, M and Weimer, LE and Bonfanti, P and Forte, AL and Cogliandro, V and Bottaro, V and Andreozzi, P and Zucco, S and Vagheggini, G and Onder, G},
title = {Cognitive impairment in long-COVID: frequency, trajectories and risk factors in a cohort study from Italy.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {5},
pages = {},
pmid = {42010131},
issn = {1590-3478},
support = {I85F21003410005//Ministero della Salute/ ; },
}

@article {pmid42010493,
year = {2026},
author = {Köhrer, S and Brand, ML and Leidner, V and Zimmer, H and Langel, A and Langel, J and Michl, P and Mohr, I},
title = {Exploratory longitudinal cohort study of modest bilirubin-driven biochemical liver alterations after SARS-CoV-2 infection in a selected subgroup of patients with Wilson's disease and liver cirrhosis.},
journal = {BMC gastroenterology},
volume = {26},
number = {1},
pages = {},
pmid = {42010493},
issn = {1471-230X},
}

@article {pmid42011141,
year = {2026},
author = {Lloyd-Jones, G and Santamarina, M and Alcock, R and Oudkerk, M},
title = {Acute COVID-19 lung disease and long COVID vascular pathophysiology modelling: the relevance of medical imaging in building multidisciplinary understanding.},
journal = {The British journal of radiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/bjr/tqag056},
pmid = {42011141},
issn = {1748-880X},
abstract = {In this review, imaging features of COVID-19 lung disease are analysed in the context of pathophysiological processes in different phases of the disease. Radiological evidence is presented for the central role of vasculopathic phenomena in both the acute and post-acute phases of COVID-19. Radiologists have a central role in building understanding of many diseases. In multidisciplinary settings, medical imaging has a role in diagnosing, assessing severity, monitoring progress and delineating anatomy involved in diseases. Imaging also helps to elucidate models of disease pathogenesis. At the outset of the COVID-19 pandemic many groups worked together informally to gain understanding of pathogenesis, but no centralised system for formal interdisciplinary collaboration existed. In hindsight, the absence of formalised radiological involvement in building models of pathophysiology potentially contributed to the use of terminology which may be considered inappropriate or misleading. We reflect on the use of certain terminology commonly used to describe the lung disease. In conclusion, imaging is essential to multidisciplinary understanding of COVID-19 vascular pathophysiology both in the acute and post-acute phases of disease. Formation of collaborative systems to build interdisciplinary understanding of disease pathogenesis across all medical and scientific specialties should be a priority at the outset of any future pandemic.},
}

@article {pmid42011214,
year = {2026},
author = {Tan, C and Meng, J and Dai, X and He, B and Liu, P and Wu, Y and Xiong, Y and Yin, H and Wang, S and Gao, S},
title = {Corrigendum to 'Effects of therapeutic interventions on long COVID: a meta-analysis of randomized controlled trials'.},
journal = {EClinicalMedicine},
volume = {94},
number = {},
pages = {103887},
pmid = {42011214},
issn = {2589-5370},
abstract = {[This corrects the article DOI: 10.1016/j.eclinm.2026.103883.][This corrects the article DOI: 10.1016/j.eclinm.2026.103882.][This corrects the article DOI: 10.1016/j.eclinm.2025.103412.].},
}

@article {pmid42013972,
year = {2026},
author = {Sagoo, R and Sagoo, NS and Nguyen, K and Sathyamoorthy, M},
title = {Sex-Based Differences in Cardiovascular Diagnoses, Mortality, and Resource Utilization in Long COVID Hospitalizations: A National Inpatient Sample Analysis.},
journal = {The American journal of cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjcard.2026.04.027},
pmid = {42013972},
issn = {1879-1913},
abstract = {Long COVID refers to persistent sequelae following SARS-CoV-2 infection, and sex-specific cardiovascular outcomes among hospitalized patients remain incompletely characterized. We queried the 2022 National Inpatient Sample (NIS) to identify adult hospitalizations with a diagnosis of long COVID (ICD-10 U09.9), excluding patients younger than 18 years or with missing outcome data. Analyses incorporated NIS discharge weights to generate national estimates. Multivariable (survey-weighted) logistic regression was used to estimate adjusted odds ratios (aORs) for cardiovascular diagnoses and in-hospital mortality. Among 87,415 weighted hospitalizations for long COVID, 49.4% were male and 50.6% were female. Males had more complicated hypertension, coagulopathy, and alcohol use disorder, whereas females had higher rates of obesity, depression, and hypothyroidism (all p<0.05). Males had a higher in-hospital mortality rate (5.9% vs. 4.7%, p<0.001). In adjusted analyses, females had lower odds of in-hospital mortality (aOR: 0.874 [95% CI, 0.819-0.932]), cardiac arrhythmias (aOR: 0.652 [0.629-0.677]), venous thromboembolism (aOR: 0.846 [0.807-0.887]), and myocardial infarction (aOR: 0.767 [0.720-0.817]). Adjusted odds of ischemic cerebrovascular accident were not significantly different (aOR: 0.955 [0.795-1.146]). Females had higher odds of transient ischemic attack (aOR: 1.441 [1.067-1.945]). Median length of stay (5 vs. 4 days) and total hospital charges ($50,447 vs. $43,839) were lower in females (all p<0.001). In conclusion, in this nationally representative analysis of long COVID hospitalizations, sex-based differences were observed in cardiovascular diagnoses, mortality, and healthcare utilization, and these findings support sex-sensitive risk stratification and hypothesis generation for post-COVID care.},
}

@article {pmid42001973,
year = {2026},
author = {Mery, V and Albacar, N and Matute-Villacís, M and Dalmases, M and Sibila, O and Agustí, À and Embid, C},
title = {"High prevalence of obstructive sleep apnea in patients with Long-COVID".},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108848},
doi = {10.1016/j.rmed.2026.108848},
pmid = {42001973},
issn = {1532-3064},
abstract = {BACKGROUND: Long-COVID (LC) is defined as the persistence of symptoms 12 weeks after the acute COVID infection not explained by any other alternative diagnosis. Its pathophysiology is poorly understood. Obstructive Sleep Apnea (OSA) shares several clinical manifestations with LC, such as fatigue and low-quality sleep, however, thus far, their potential coexistence has been poorly addressed.

OBJECTIVE: To investigate the prevalence of OSA in patients with LC.

METHODS: Observational, prospective study. Patients with LC were recruited from a dedicated ambulatory hospital clinic. All patients underwent a comprehensive clinical evaluation, including standardized questionnaires to evaluate persistent symptoms, lung function tests and full polysomnography.

RESULTS: We studied 73 patients with LC. Their mean age was 57.4 ± 10.5 years, they were predominantly male (56.2%), 73.9% of whom were hospitalized during the acute COVID episode. Median AHI was 17.2 (24.14) events/h with a proportion of mild (27.4%), moderate (24.6%) and severe OSA (31.5%). Objective questionnaires identified poor sleep quality and fatigue as the most prevalent symptoms and daytime sleepiness as the least prevalent. Self-reported symptoms were frequent, with dyspnea, fatigue, and insomnia being the most commonly reported. Neither objective nor subjective symptoms correlated with OSA severity, with the exception of insomnia.

CONCLUSION: In this single-center, clinic-based LC cohort, OSA diagnosed by in-lab PSG was highly common. Given that OSA is treatable, a sleep study should be considered in LC patients even in the absence of daytime sleepiness or in the presence of insomnia.},
}

@article {pmid42004170,
year = {2026},
author = {Li, Y and Shan, T and Jiang, Z and Han, F and Ma, J and Ni, H and Peng, J and Xu, M},
title = {Enduring coagulopathy and endothelial dysfunction in postacute COVID-19 syndrome.},
journal = {Blood vessels, thrombosis & hemostasis},
volume = {3},
number = {2},
pages = {100147},
pmid = {42004170},
issn = {2950-3272},
abstract = {Postacute coronavirus disease 2019 (COVID-19) syndrome (PACS), or long COVID, encompasses a range of symptoms persisting beyond the acute phase of severe acute respiratory syndrome coronavirus 2 infection. Although acute-phase coagulation disturbances in COVID-19 are well documented, these abnormalities during recovery and their association with PACS remain inadequately explored. Our study aimed to investigate the long-term changes in coagulation function and inflammatory markers in patients with PACS, elucidating their pathological mechanisms and providing insights for patient management. This retrospective cohort study included 3783 adult inpatients in Jinan, China, divided into COVID-19-positive and -negative groups, with 363 patients with COVID-19 further diagnosed with PACS. Coagulation and inflammatory markers were collected at baseline and during 1-year follow-up, and changes over time were analyzed using generalized estimating equations. Most inflammatory markers and some coagulation parameters showed significant recovery, including lymphocyte counts and fibrinogen. However, several parameters remained abnormal even at 7 to 12 months after infection. Of note, D-dimer (Z = 5.692, P < .001, abnormal rate 65.79%) and erythrocyte sedimentation rate (Z = 2.749, P = .006, abnormal rate 57.32%) remained elevated above the normal upper limit. Additionally, certain coagulation parameters, particularly prothrombin time (β = -0.10 [95% confidence interval, -0.88 to 0.69]; P = .81, prolonged rate 17.29%) and platelet counts, did not normalize by 7 to 12 months. Our findings in survivors of severe COVID-19 pneumonia support the concept of PACS as a chronic thromboinflammatory syndrome characterized by sustained coagulation abnormalities. The prolonged elevation of D-dimer and incomplete recovery of coagulation parameters highlight the need for long-term monitoring and personalized management strategies to mitigate thrombotic risks in survivors of COVID-19.},
}

@article {pmid42004496,
year = {2026},
author = {Omdal, R and Lenning, OB and Jonsson, G and Kvaløy, JT and Skoie, IM and Braut, GS and Grimstad, T},
title = {Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.},
journal = {Brain, behavior, & immunity - health},
volume = {54},
number = {},
pages = {101226},
pmid = {42004496},
issn = {2666-3546},
abstract = {BACKGROUND: Fatigue persists as a dominant and debilitating phenomenon in long-COVID, yet its underlying biological mechanisms remain unclear. While inflammatory variables tend to normalize within months post-infection, fatigue continues to significantly impact quality of life. Understanding whether specific biomarkers associate with long-COVID fatigue could shed light on pathophysiological mechanisms and potential therapeutic targets.

METHODS: In this single-center, cross-sectional controlled study, we enrolled 48 individuals with long-COVID (according to NICE criteria) and 48 age- and sex-matched recovered controls with prior SARS-CoV-2 infection but no persistent symptoms. We carefully excluded all subjects with other diseases or conditions that could influence fatigue levels. Fatigue severity was assessed using three validated instruments: Fatigue Visual Analog Scale (fVAS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and SF-36 vitality subscale. Blood samples were analyzed for pro-inflammatory markers (CRP, TNF-α, IL-6, IL-1β) and biomarkers associated with cellular stress responses and neuroprotection (HSP90α, APOA4, Serpin F1/PEDF, Hemopexin). Anti-nuclear antibodies (ANA) were tested to assess potential autoimmune mechanisms. Depression was assessed using the Hospital Anxiety and Depression Scale, Depression Subscale (HADS-D).

RESULTS: Long-COVID patients demonstrated significantly higher fatigue severity across all instruments compared to recovered controls: fVAS median scores 63 versus 5 (p < 0.001), FACIT-F scores 21.5 versus 49 (p < 0.001), and SF-36 vitality scores 25 versus 72.5 (p < 0.001). Depression scores were also significantly elevated in long-COVID cases. However, none of the measured biomarkers differed significantly between groups: HSP90α, Serpin F1, Hemopexin, APOA4, and CRP showed no differences, while TNF-α and IL-6 showed only tendencies toward higher levels in long-COVID (p = 0.07 and p = 0.07, respectively). IL-1β concentrations were in most cases below the lower limit of detection and were excluded from further analysis. ANA positivity was 10.4% in cases versus 4.2% in controls (p = 0.38) and did not influence fatigue levels. Multivariable regression analysis revealed no significant associations between biomarkers and fatigue severity.

CONCLUSIONS: Fatigue in long-COVID represents severe, persistent disability comparable to observations in chronic inflammatory diseases and chronic fatigue syndrome but is not associated with traditional inflammatory biomarkers or cellular stress response proteins measured in peripheral blood. The absence of biomarker associations suggests that long-COVID fatigue may involve more complex mechanisms, potentially including persistent neuro-immune dysregulation, epigenetic changes, or pathophysiological processes not reflected in systemic biomarker concentrations including neurobiological mechanisms such as altered predictive processing and central nervous system-confined neuroinflammation. These findings highlight the need for alternative approaches to understanding and treating long-COVID fatigue beyond conventional inflammatory paradigms.},
}

@article {pmid42004523,
year = {2026},
author = {Petranu, K and Ford, T and Henley, D and Hammond, E and Henley, J and Crawford, M and Coleman, Z and Hirschtick, J},
title = {Exploring Long COVID diagnostic equity by sex, race and ethnicity, and insurance type.},
journal = {Preventive medicine reports},
volume = {65},
number = {},
pages = {103459},
pmid = {42004523},
issn = {2211-3355},
abstract = {OBJECTIVE: Our study explored Long COVID diagnostic inequity by comparing the demographic profile of patients diagnosed with Long COVID to patients diagnosed with COVID-19.

METHODS: Using electronic health record data from Advocate Health-Midwest between March 1, 2020, to November 1, 2023, we compared the proportion of all patients with documentation of Long COVID versus COVID-19 by race/ethnicity, sex, insurance type, and varying combinations of these characteristics.

RESULTS: Relative to COVID-19, a greater proportion of patients diagnosed with Long COVID were female (63.7% vs. 58.0%), non-Hispanic (NH) White (66.4% vs 62.9%), or covered by private insurance (53.8% vs 51.3%), and a lower proportion were Hispanic (12.1% vs. 14.3%) or covered by Medicaid (11.9% vs. 14.3%). Among patients with Medicaid, NH Black patients were underrepresented by 5.4 percentage points in the Long COVID sample vs. COVID-19 (25.2% vs. 30.6%), while NH White patients were overrepresented by 6.7 percentage points in the Long COVID sample compared to COVID-19 (48.2% vs. 41.5%).

CONCLUSIONS: Long COVID diagnostic estimates may be skewed towards patients that are more willing and able to seek care, while patients who experience multiple forms of disadvantage may be at risk for underdiagnosis due to compounding barriers to diagnosis.},
}

@article {pmid42007006,
year = {2026},
author = {Tamariz, L and Milanes, I and Bast, E and Shehadeh, LA and Klimas, N and Palacio, A},
title = {Elevated blood viscosity is associated with dysautonomia in long COVID symptoms.},
journal = {American heart journal plus : cardiology research and practice},
volume = {65},
number = {},
pages = {100776},
pmid = {42007006},
issn = {2666-6022},
abstract = {BACKGROUND: Long COVID is associated with elevated inflammatory and antibody levels. Elevated plasma proteins can increase blood viscosity and decrease blood flow. Our aim is to evaluate if blood viscosity is associated with long COVID outcomes.

METHODS: We conducted a cross-sectional study and included a sample of patients enrolled in our long COVID clinic. We estimated whole blood viscosity (WBV) using two previously validated formulas and compared it with the NASA lean test, COMPASS-31 scale as measures of dysautonomia and the symptom burden as measured by the modified COVID-19 Yorkshire scale. We obtained WBV at three different shear stress. We divided WBV and evaluated the distribution of symptom scores using univariate and multivariate models.

RESULTS: We included 185 patients for this study. Our sample had a mean age of 56 ± 11 years, included 53% minorities and 32% were women. The mean C19-YRSm did not change with increasing tertile of WBV (p > 0.05) while the mean COMPASS-31 score increased with increasing tertile of WBV in all levels of shear stress. In adjusted models the beta-coefficient of the C19-YRSm was (B -0.19p = 0.90) and for COMPASS-31 was (B 7.0 p = 0.01) for 208 s[-1] and for all other levels of shear stress Twenty-three percent of patients in tertile 1 had either POTS or orthostatic hypotension compared to 32% on tertile 3 (p = 0.04).

CONCLUSION: Whole blood viscosity was associated with dysautonomia and not with long COVID symptoms.},
}

@article {pmid41998026,
year = {2026},
author = {Chowdhury, MMH and Quenum, AJI and Rioux-Perreault, C and Lucier, JF and Ilangumaran, S and Piché, A and Allard-Chamard, H and Ramanathan, S},
title = {Distinct plasma proteome signature at 3 months post-COVID-19 infection irrespective of post-COVID condition.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-46180-y},
pmid = {41998026},
issn = {2045-2322},
support = {GA4-177773/CAPMC/CIHR/Canada ; 202309PPE-512214/CAPMC/CIHR/Canada ; },
abstract = {Persistent symptoms following SARS-CoV-2 infection are the hallmark of post-COVID condition (PCC), also referred to as long COVID. However, the underlying molecular mechanisms remain poorly understood. In this study, we employed data-independent acquisition mass spectrometry (DIA-MS)-based plasma proteomics to identify molecular alterations associated with PCC. DIA-MS proteomic analysis revealed a clear distinction between the plasma proteome of uninfected individuals and those previously infected with SARS-CoV-2, irrespective of PCC status. PCC samples demonstrated downregulation of the antioxidant protein peroxiredoxin 6 (PRDX6) and upregulation of oxidative stress-associated proteins, particularly vanin-1 (VNN1) and paraoxonase-3 (PON3). Additionally, individuals with PCC exhibited significantly elevated levels of six proteins-PCSK9, CST3, C1Q, CPB2, KNG1, and GAPDH-associated with glycolysis, complement and coagulation cascades, and inflammatory pathways. Validation by ELISA does not necessarily reflect the proteomics data suggesting the requirement for alternate methods of validation. Nonetheless, oxidative stress, as measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG), further showed that PCC samples had significantly higher levels of DNA damage, compared with convalescent individuals. Antioxidant markers, including reduced and oxidized glutathione (GSH and GSSG), were significantly lower in PCC samples than in uninfected controls. Collectively, these findings indicate that plasma proteomic alterations persist for at least 3 months following SARS-CoV-2 infection, with additional disruptions in oxidative stress and inflammatory pathways characterizing individuals with PCC.},
}

@article {pmid41993482,
year = {2026},
author = {Lu, P and Izzy, S and Da Silva, P and Imkamp, HT and Christenson, JR and Yahya, T and Mansi, MHA and Alawi, A and Moreira, TG and Monje, M and Weiner, HL and Iwasaki, A},
title = {Intranasal Anti-CD3 Antibody Treatment Attenuates Post-COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.07.716934},
pmid = {41993482},
issn = {2692-8205},
abstract = {Cognitive impairment is a disabling feature of Long COVID, with data supporting neuroinflammation and maladaptive glial responses as primary drivers. Nasal administration of an anti-CD3 monoclonal antibody (aCD3 mAb) has shown therapeutic benefits in autoimmune and CNS disease models. Using a respiratory-restricted mild SARS-CoV-2 mouse model of Long COVID, we show that nasal anti-CD3 mAb, administered shortly after infection or during chronic neuroinflammation, increased brain FoxP3+ IL-10+ Tregs, reduced microglial and astrocytic gliosis in the white matter and hippocampus, restored neurogenesis, and improved short-term memory. Nasal aCD3 mAb reprogrammed microglia from an antigen-presenting, NF-κB-driven inflammatory state toward chemokine signaling, phagosome, and TGF β-related regulatory phenotype. Patients with Long COVID with neurological symptoms had lower circulating Treg populations. These findings identify nasal administration of aCD3 mAb as a noninvasive strategy to control neuroinflammation, restore the neurogenic niche, and offer a novel approach to treating cognitive impairment in Long COVID.},
}

@article {pmid41993604,
year = {2026},
author = {Colgan, DD and Buttolph, L and Grow, T and Stadler, DD and Ruddick, M and Davenport, TE and Zwickey, H},
title = {Designing Nutrition Studies for Long COVID and Related Infection-Associated Chronic Illness: Qualitative Insights From a Patient-Reported Evaluation of Ketogenic Metabolic Therapy.},
journal = {Journal of patient experience},
volume = {13},
number = {},
pages = {23743735261442541},
pmid = {41993604},
issn = {2374-3735},
abstract = {BACKGROUND: Long COVID affects over 400 million people worldwide and has no FDA-approved treatments. Patients often rely on self-directed strategies, making their lived experiences an essential, yet underutilized, source of evidence. Ketogenic metabolic therapy (KMT) has demonstrated mechanisms relevant to Long COVID, including improved mitochondrial energy production, reduced oxidative stress, and modulation of inflammation, but remains underexplored.

METHODS: We conducted a cross-sectional, mixed-methods study of adults who completed Enable Your Healing, a 12-week virtual program integrating KMT with lifestyle components. Recruitment emails were sent to 194 participants; 41 completed the online REDCap survey. Quantitative data were summarized descriptively. Qualitative data were analyzed using conventional content analysis.

RESULTS: Participants (mean age 41; 90% female) reported diagnoses including postviral dysautonomia, myalgic encephalomyelitis/chronic fatigue syndrome, and Long COVID. Four themes emerged: program benefits, challenges, recommendations, and scientific considerations. Key insights included the value of multicomponent synergy, extended duration, and prioritization of functional outcomes.

CONCLUSION: Findings suggest nutrition trials for infection-associated chronic illnesses, including Long COVID, should consider incorporating longer intervention periods, multicomponent design, patient-centered outcomes, lived-experience integration, and tailored supports to optimize feasibility and impact.},
}

@article {pmid41993998,
year = {2026},
author = {Mogensen, DG and Dreyer, P and Backer, V and Jarden, M},
title = {Living with a hidden disability - a qualitative study of post-COVID-19 olfactory dysfunction.},
journal = {Frontiers in allergy},
volume = {7},
number = {},
pages = {1792460},
pmid = {41993998},
issn = {2673-6101},
abstract = {INTRODUCTION: Since the onset of the COVID-19 pandemic, olfactory dysfunction has become increasingly prevalent, manifesting as complete loss of smell, reduced olfactory sensitivity, or distorted perceptions such as parosmia. This qualitative study explored how post-COVID-19 olfactory dysfunction is experienced and how it impacts daily life, well-being, and quality of life.

METHODS: A qualitative design inspired by Ricoeur's phenomenological-hermeneutic approach was used. Twenty patients with post-COVID-19 olfactory dysfunction were recruited from an otolaryngology department in Denmark and interviewed between June 2023 and February 2024. Transcribed data were analyzed using Dreyer and Pedersen's Ricoeur-inspired method. The Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist was applied.

RESULTS: The analysis revealed six themes: 1) Smell loss means relying on others' sense of smell, 2) A sudden fear of body odor, 3) The smell of decay and dreadful taste take over, 4) Losing the pleasure of food and finding comfort in overeating, 5) The loss of the ability to recall and experience meaningful scents, and 6) Living with a hidden disability.

CONCLUSIONS: Olfactory dysfunction after COVID-19 is experienced as an invisible yet intrusive condition that impacts daily functioning, eating habits, social relationships and personal identity. The findings highlight the need for greater awareness among healthcare professionals to support patients in developing coping strategies that promote quality of life in the context of long-term sensory loss.},
}

@article {pmid41994117,
year = {2026},
author = {Byrareddy, S and Kumar, N and Acharya, A and Das, R and Sardarni, U and Olasunkanmi, O and Murakonda, S and Sutar, D and Venkatesan, A and Ampasala, D and Cohen, S and Samuelson, M and Sajja, B and Dettmer, U and Ramalingam, N and Chand, H},
title = {Sex- and Age-Dependent Neuroimmune Dysregulation and Early Neurodegenerative Signatures Following SARS-CoV-2 Infection in Golden Syrian Hamsters.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9130692/v1},
pmid = {41994117},
issn = {2693-5015},
abstract = {Post-acute sequelae of SARS-CoV-2 infection, or Long-COVID, affects millions globally and is characterized by persistent symptoms affecting multiple organs, yet the underlying mechanisms remain poorly defined. Here, we used Golden Syrian Hamsters (GSH) infected with the SARS-CoV-2 to investigate how sex and age shape viral persistence, organ-specific pathology, immune responses, and neurological outcomes during acute infection and Long-COVID. We show that during Long-COVID, viral RNA persists only in the lungs of male hamsters. Lung pathology revealed sustained inflammation and tissue remodeling, with young females exhibiting greater fibrosis. Transcriptomic profiling across brain, lung, and heart identified pronounced sex- and age-dependent regulation of gene expression spanning immune, neuroinflammatory, and neurotransmitter signaling pathways. These transcriptomic alterations were accompanied by sex-specific behavioral changes and persistent microstructural remodeling in cognition-associated brain regions. Additionally, SARS-CoV-2 altered α-synuclein homeostasis and microglial activation alongside gut microbiome composition in a sex- and age-dependent manner. Together, our findings demonstrate that, in GSH Long-COVID is strongly modulated by sex and age, influencing viral RNA persistence, immune and neurobiological responses, and gut microbiota composition mirroring clinical outcomes reported in human cohorts. This study establishes SARS-CoV-2-infected GSH as a model for dissecting the mechanisms of Long-COVID and informing targeted prevention strategies.},
}

@article {pmid41995128,
year = {2026},
author = {Gonah, L and Ginindza, TG and Hlongwana, KW},
title = {Mapping global evidence on compassion fatigue among healthcare workers during COVID-19: insights and implications for future preparedness - a scoping review.},
journal = {Journal of global health},
volume = {16},
number = {},
pages = {04130},
doi = {10.7189/jogh.16.04130},
pmid = {41995128},
issn = {2047-2986},
mesh = {Humans ; *COVID-19/epidemiology/psychology ; *Health Personnel/psychology ; *Compassion Fatigue/epidemiology ; Risk Factors ; SARS-CoV-2 ; Prevalence ; Global Health ; Burnout, Professional/epidemiology ; Female ; },
abstract = {BACKGROUND: Compassion fatigue (CF) is a critical occupational hazard for healthcare workers (HCWs), intensified by the COVID-19 pandemic, with implications for well-being, retention, and quality of care. We aimed to map the global evidence on CF prevalence, risk factors, effects, interventions, and research gaps among HCWs during the COVID-19 pandemic.

METHODS: A scoping review of 56 studies from 21 countries (2020-2025) was conducted following PRISMA-ScR guidelines. Seven databases were searched, and findings were synthesised narratively with attention to occupational, demographic, and systemic determinants of CF.

RESULTS: Compassion fatigue prevalence ranged from 20 to 87%. It was most pronounced among nurses, women, frontline staff, early-career professionals, and those in under-resourced or rural settings. Key risk factors included high workload, long shifts, repeated exposure to death, moral distress, and limited organisational support. Symptoms encompassed emotional exhaustion, depersonalisation, diminished empathy, and co-occurring anxiety, depression, or secondary traumatic stress. Interventions (resilience and peer-support programmes, self-compassion training, motivational messaging, and mobile psychoeducation) showed small-to-moderate benefits but were limited by methodological heterogeneity and scarce robust evaluation. Temporally, CF peaked during early pandemic surges and persisted among frontline staff and in resource-constrained or long-COVID contexts.

CONCLUSIONS: Compassion fatigue is a multifactorial, context-dependent hazard disproportionately affecting vulnerable HCWs. Effective mitigation requires longitudinal research, inclusive global representation, and multi-level strategies linking individual resilience with organisational reform and policy action to safeguard HCW well-being in current and future crises.},
}

Humans
*COVID-19/epidemiology/psychology
*Health Personnel/psychology
*Compassion Fatigue/epidemiology
Risk Factors
SARS-CoV-2
Prevalence
Global Health
Burnout, Professional/epidemiology
Female

@article {pmid41997565,
year = {2026},
author = {Rozewicz-Juraszek, M and Mueller, S and Ganbat, M and Bolanos, CR and Klement, A and Ugalde, SA and Halle, M and Nagel, E and Puntmann, V},
title = {Native T1 is independently associated with aerobic exercise capacity in long-term follow-up after mild initial COVID-19 disease (Impression COVID&Heart Study).},
journal = {Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance},
volume = {},
number = {},
pages = {102725},
doi = {10.1016/j.jocmr.2026.102725},
pmid = {41997565},
issn = {1532-429X},
abstract = {BACKGROUND: Exercise intolerance is a common and incapacitating long-term consequence of COVID-19, even after mild acute illness. Cardiovascular magnetic resonance (CMR) studies have demonstrated persistent perimyocardial inflammatory abnormalities; however, their relationship with long-term aerobic capacity remains unclear.

METHODS: In this prospective observational study, individuals without prior structural heart disease underwent standardised CMR, echocardiography, and cardiopulmonary exercise testing (CPET) at least 3 years after the initial COVID-19. The primary endpoint was the association between %-predicted VO₂peak (age-sex-body mass index (BMI) adjusted, Study of Health in Pomerania (SHIP) reference) and imaging parameters. Secondary analyses included lactate measurements and sex-stratified models.

RESULTS: A total of 132 participants (mean age 49 ± 12 years; 68/132 (52%) male) were evaluated 48 months [interquartile range (IQR) 42-53] post-infection. Non-ischaemic perimyocardial enhancement was present in 34/132 (26%), whereas two participants had an unrecognised ischaemic scar. Male sex, higher BMI, lower age, and higher native T1 were associated with lower %-predicted VO₂peak in univariate models. In multivariate analysis, male sex, lower age, and higher native T1 (β = -0.25 per ms, 95% CI -0.40 to -0.10; p < 0.001) remained independent predictors of lower %-predicted VO₂peak. In total, 63/132 (48%) participants demonstrated %-predicted VO₂peak below predicted values. Sex-stratified multivariate analyses showed that higher native T1 (p<0.001) independently associated with lower %-predicted VO₂peak in both men and women, with lower age additionally retained in men. In a lactate-measured subgroup (n=73), higher resting lactate, higher native T1, male sex, and lower left atrial area were associated with lower %-predicted VO₂peak.

CONCLUSIONS: In long-term follow-up of individuals with mild initial COVID-19 and no prior structural heart disease, aerobic capacity relative to predicted values was reduced in 48% of participants, particularly in men, and was independently associated with higher myocardial native T1. Native T1 and resting lactate, but not conventional structural measures or peak exercise.},
}

@article {pmid41987304,
year = {2026},
author = {Alhumaid, S and Sabr, Z and Alshehri, SM and Alhashem, HA and Alnajjad, Q and Alsaadoun, DS and Algrafi, AS and Aborshaid, FA and Alsaidalani, AA and Noorsaeed, S and Al Nasser, DA and Majzoub, RA and Alkhars, O and Al Dossary, N and Banjar, SS and ALMuhaini, IA and Ismail, FA and Al Alawi, Z and Alalwan, QM},
title = {Asthma control and exacerbation risk following SARS-CoV-2 infection in the post-acute COVID-19 phase: a systematic review.},
journal = {Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13223-026-01027-z},
pmid = {41987304},
issn = {1710-1484},
}

@article {pmid41987944,
year = {2026},
author = {Mesquita da Fonseca, L},
title = {Commentary: A cross-continental comparative analysis of the neurological manifestations of Long COVID.},
journal = {Frontiers in human neuroscience},
volume = {20},
number = {},
pages = {1798243},
pmid = {41987944},
issn = {1662-5161},
}

@article {pmid41990057,
year = {2026},
author = {Zhang, J and Zhao, W and Zhang, T and Wu, Q and Di, J and Mao, X},
title = {Impact of COVID-19 on the treatment outcomes of secretory otitis media.},
journal = {Journal of infection in developing countries},
volume = {20},
number = {3},
pages = {327-331},
doi = {10.3855/jidc.21341},
pmid = {41990057},
issn = {1972-2680},
mesh = {Humans ; *COVID-19/complications/epidemiology ; Male ; Female ; Retrospective Studies ; Treatment Outcome ; Middle Aged ; Adult ; *Otitis Media with Effusion/therapy/complications/drug therapy ; SARS-CoV-2 ; Aged ; Audiometry, Pure-Tone ; },
abstract = {INTRODUCTION: The World Health Organization (WHO) officially lifted the global emergency designation for coronavirus disease 2019 (COVID-19) in May 2023. Nonetheless, the long-term repercussions of the pandemic-referred to as 'long COVID'-have persisted. It is also highly likely for the disease to be complicated by secretory otitis media (SOM). This study aimed to determine if there is anything particularly distinctive about SOM associated with long-COVID, and could it affect the therapeutic outcomes of the latter.

METHODOLOGY: A total of 102 patients diagnosed with COVID-19-associated SOM between December 2022 and May 2023 were retrospectively analyzed. Pre- and post-treatment pure-tone audiometry thresholds were assessed to evaluate therapeutic efficacy. Follow-up assessments were performed at 1, 3, 6, and 12 months' post treatment, and the findings were compared with those of a control group of 98 patients who had SOM but not COVID-19 infection during the same time frame.

RESULTS: All patients showed normal hearing thresholds post treatment. A comparative analysis using a two-sample t-test revealed no statistically significant difference in the average speech-hearing thresholds between the two groups post-treatment (t = 0.099, p = 0.92). No recurrence was observed in either group during the year-long follow-up period.

CONCLUSIONS: Although COVID-19 is commonly associated with SOM, patients can expect satisfactory recovery of their hearing function with proactive treatment strategies.},
}

Humans
*COVID-19/complications/epidemiology
Male
Female
Retrospective Studies
Treatment Outcome
Middle Aged
Adult
*Otitis Media with Effusion/therapy/complications/drug therapy
SARS-CoV-2
Aged
Audiometry, Pure-Tone

@article {pmid41991929,
year = {2026},
author = {Saak, TM and Tervo, JP and Jacobson, PT and Vilarello, BJ and Caruana, FF and Gallagher, LW and Gary, JB and Gudis, DA and Motter, JN and Goldberg, TE and Devanand, DP and Overdevest, JB},
title = {Longitudinal evaluation of neurocognitive outcomes in a cohort with persistent post-COVID olfactory dysfunction.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {41991929},
issn = {2045-2322},
abstract = {Persistent COVID-19-associated olfactory dysfunction (C19OD), along with other neurologic and cognitive deficits are common features of long COVID. This study aims to evaluate longitudinal trends in neurocognitive performance within a cohort with C19OD. In individuals with perceived C19OD we performed serial psychophysical olfactory and neurocognitive assessments at baseline and follow-up one year later. At baseline evaluation, individuals with C19OD were found to have diminished cognitive functioning compared to normosmic counterparts across several domains, including attention, executive functioning, language, learning and memory, and psychomotor speed. At subsequent one-year follow-up assessment, C19OD participants demonstrated cognitive recovery, with performance comparable to normosmic counterparts. These findings suggest that early associations between C19OD and certain neurocognitive domains may dissipate upon repeated longitudinal evaluation, with partial resolution of cognitive deficits despite persistent C19OD.},
}

@article {pmid41982416,
year = {2026},
author = {Doenyas-Barak, K and Elman Shina, K and Lang, E and Finci, S and Elkarif, V and Shorer, R and Efrati, S},
title = {The effect of hyperbaric oxygen therapy on sleep quality across diverse patient populations.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1690633},
pmid = {41982416},
issn = {1664-2295},
abstract = {BACKGROUND: Sleep disturbances are common in aging, post-traumatic stress disorder (PTSD), and long COVID, often linked to neuroinflammation, autonomic dysregulation, and neurodegeneration. Hyperbaric oxygen therapy (HBOT) promotes neuroplasticity through the hyperoxic-hypoxic paradox, improving cerebral perfusion, mitochondrial function, and reducing inflammation. While HBOT benefits sleep in certain conditions, its general effects across clinical populations remain unclear.

METHODS: This retrospective longitudinal study evaluated Pittsburgh Sleep Quality Index (PSQI) changes in patients undergoing 60 HBOT sessions (2.0 ATA, 100% oxygen, 90 min, 5 days/week) at the Sagol Center. Participants included individuals treated for healthy aging (n = 180), long COVID (n = 92), or PTSD (n = 123). Pre- and post-treatment PSQI total and component scores were compared using paired t-tests and Wilcoxon signed-rank test was used for PSQI components. Regression analysis identified predictors of improvement.

RESULTS: Among 395 patients (mean age at baseline 57.9 ± 14.6 years, 31% female), baseline PSQI scores were highest in PTSD. Post-HBOT, total PSQI scores improved significantly in all groups (p < 0.001; Cohen's d = 0.37-0.91). Significant gains were observed in subjective sleep quality, sleep latency, and disturbances in all groups; daytime dysfunction improved in aging and long COVID but not PTSD. Medication use was unchanged. Baseline PSQI was a strong predictor of improvement (B = 0.494, p < 0.001, r = 0.46). Those with disturbed sleep (PSQI>5) showed broad, statistically significant gains, while normal sleepers exhibited minimal changes.

CONCLUSION: HBOT was associated with improvement in sleep quality across diverse conditions, with greatest benefit in patients with poorer baseline sleep. Findings support HBOT's potential as a sleep-modulating therapy, warranting controlled trials to characterize the patients that can benefit the most and elucidate mechanisms.},
}

@article {pmid41984770,
year = {2026},
author = {Abbas, U and Laghari, RN and Ahmed, I and Musawwir, UA and Riaz, H and Anwar, K and Hussain, N and Mubeen, M and Khan, M and Khalid, MU and Ashraf, S},
title = {Acute SARS-CoV-2 viral load and systemic inflammation are associated with neuropsychiatric and musculoskeletal symptoms in long COVID.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0346978},
doi = {10.1371/journal.pone.0346978},
pmid = {41984770},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/complications/virology/blood/psychology ; *Viral Load ; Male ; Female ; Middle Aged ; Retrospective Studies ; *SARS-CoV-2/isolation & purification ; *Inflammation/blood/virology ; Adult ; Biomarkers/blood ; Aged ; *Musculoskeletal Diseases ; Interleukin-6/blood ; *Mental Disorders ; C-Reactive Protein/metabolism ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long after recovery from acute-COVID illness, many patients show persistent multi-organ dysfunction consistent with Long COVID. Biochemical profile and measurements of inflammatory markers in these individuals can help to understand the underlying pathophysiology. This study aims to evaluate biochemical markers and their association with symptoms of Long COVID. We, in a retrospective analysis, also examined whether the Long COVID symptom persistence is associated with the SARS-CoV-2 viral load documented during the acute infection.

METHODS: A total of 300 participants with previously diagnosed mild COVID-19 were recruited at 10 months post-infection. Brief clinical history was taken based on persistent symptoms after COVID-19 and categorized as Long COVID (n = 177) and controls group (n = 123) based on WHO defined criteria. Biochemical parameters in blood like complete blood count (RBC and WBC indices) were compared between the groups. Other measurements including inflammatory markers such as IL-6, IL-10, ferritin and C-reactive protein along with electrolytes, vitamin D3 and B12, and lipid profile, were also compared. SARS-CoV-2 viral load was assessed retrospectively. Data was analyzed through SPSS v.26.

RESULTS: The findings of our study revealed that 59% (177) of individuals had symptoms of Long COVID. The most frequently reported symptoms of Long COVID were related to neuropsychiatry (35%), followed by musculoskeletal system (32.2%). The Hemoglobin, RBC counts and MCHC were decreased in Long COVID as compared to control group (p < 0.05). While Lymphocytes, IL-6 and ferritin levels were raised in Long COVID group (p < 0.05). In multivariable logistic regression analyses adjusted for age and sex, neuropsychiatric symptoms were independently associated with higher lymphocyte counts (aOR 1.19, 95% CI 1.12-1.51), IL-6 (aOR 1.16, 95% CI 1.10-1.86), ferritin (aOR 1.42, 95% CI 1.10-1.53), and vitamin D deficiency (aOR 1.45, 95% CI 1.22-2.01). Musculoskeletal symptoms were strongly associated with vitamin D deficiency (aOR 2.30, 95% CI 1.20-4.50) and ferritin levels (aOR 0.98, 95% CI 0.97-0.99). Moreover, higher SARS-CoV-2 viral load (CT ≤ 20) during acute infection was also associated with neuropsychiatric and musculoskeletal symptoms of Long COVID.

CONCLUSION: We identified Long COVID in 59% of the participants, the highest reported percentage in studies in the middle-aged individuals. Compared to controls, we found differential biochemical markers in the Long COVID group indicating a different metabolic status in these individuals. Moreover, the association of raised inflammatory markers at ten months follow up and acute-phase SARS-CoV-2 viral load were also seen to be associated with musculoskeletal and neuropsychiatric symptoms of the Long COVID. These significant clinical and biochemical changes warrant thorough monitoring and follow-ups for extended time.},
}

Humans
*COVID-19/complications/virology/blood/psychology
*Viral Load
Male
Female
Middle Aged
Retrospective Studies
*SARS-CoV-2/isolation & purification
*Inflammation/blood/virology
Adult
Biomarkers/blood
Aged
*Musculoskeletal Diseases
Interleukin-6/blood
*Mental Disorders
C-Reactive Protein/metabolism
Post-Acute COVID-19 Syndrome

@article {pmid41984971,
year = {2026},
author = {Jason, LA and Furst, J and Katz, BZ},
title = {Comparing ME/CFS following mononucleosis with Long COVID.},
journal = {Chronic illness},
volume = {},
number = {},
pages = {17423953251347108},
doi = {10.1177/17423953251347108},
pmid = {41984971},
issn = {1745-9206},
abstract = {ObjectivesLong COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are examples of post-infectious chronic illnesses. Behavioral and pathophysiological underpinnings of both ME/CFS following IM and Long COVID are not well understood.MethodsWe studied ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. We categorized those meeting either moderate or severe ME/CFS criteria. We subsequently recruited a matched sample of those infected with SARS-CoV-2, some of whom recovered and others of whom developed Long COVID. We compared and contrasted ME/CFS and Long COVID following IM and SARS-CoV-2 infection in terms of somatic symptoms, coping strategies, depression and anxiety symptoms, and functional status.ResultsIn general, the Long COVID group's symptom burden was less than that of the Severe ME/CFS group but more than that of the Moderate ME/CFS group.DiscussionThese findings may allow investigators a better understanding of these post-viral illness pathophysiologies.},
}

@article {pmid41985377,
year = {2026},
author = {Sekendiz, Z and Caliendo, M and Taboada, D and An, T and Palekar, N and Weisenbach, S and Kim, MJ},
title = {The neuropsychiatric features of Long COVID in older adults and the potential association with neuroinflammation: Preliminary observations in a small cohort.},
journal = {Journal of the neurological sciences},
volume = {486},
number = {},
pages = {125915},
doi = {10.1016/j.jns.2026.125915},
pmid = {41985377},
issn = {1878-5883},
abstract = {BACKGROUND: The underlying mechanism of neuropsychiatric features of Long COVID remains unclear; however, the most compelling hypothesis is the contribution of excessive neuroinflammation induced by a systemic inflammatory response or cytokine storm. We aimed to investigate the neuropsychiatric features of Long COVID in older adults and the potential association with neuroinflammation measured by [[18]F]FEPPA positron emission tomography (PET) targeting translocator protein (TSPO).

METHODS: A total of 24 individuals aged 60 or older participated in the study: those with Long COVID symptoms and persistent subjective or objective cognitive impairments for more than six months (n = 12) and age-matched healthy adults without Long COVID (n = 12). After assessments with neuropsychiatric scales and cognitive testing batteries, three Long COVID and three healthy control participants, who were high-affinity binders to TSPO, underwent additional brain [[18]F]FEPPA PET scans.

RESULTS: Long COVID group (n = 12) showed significantly higher levels of depression and fatigue compared to the healthy control group (n = 12). With [[18]F]FEPPA PET, the Long COVID group (n = 3) showed significantly higher binding levels in all compared brain regions, such as the prefrontal, temporal, parietal, and occipital neocortices, and the hippocampus, thalamus, and cerebellum, compared to the healthy control group (n = 3).

CONCLUSION: Older adults with Long COVID showed greater neuropsychiatric symptoms, such as depression and fatigue, compared to healthy older adults. The [[18]F]FEPPA PET findings suggest that their persistent neuropsychiatric symptoms could potentially be associated with chronic neuroinflammation.},
}

@article {pmid41975732,
year = {2026},
author = {Fanò-Illic, G and Coscia, F and Gigliotti, PV and Checcaglini, F and Carraro, U and Fulle, S and Mancinelli, R},
title = {Pathophysiological, Translational, and Diagnostic Aspects of ME/CFS: A Focus on Skeletal Muscle Involvement.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {7},
pages = {},
pmid = {41975732},
issn = {2075-4418},
abstract = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multisystemic disorder characterized by severe, persistent fatigue not alleviated by rest and worsened by minimal exertion, often accompanied by post-exertional malaise (PEM), unrefreshing sleep, cognitive dysfunction, and autonomic disturbances. Despite decades of research, its pathophysiology remains incompletely understood, and skeletal muscle involvement has only recently gained attention. This review aims to provide a historical and pathophysiological synthesis of ME/CFS, emphasizing the pivotal role of skeletal muscle in the onset and persistence of symptoms, and to integrate molecular, cellular, and pathophysiological evidence into a coherent explanatory framework. This is a narrative review of published literature (1990-2025) with critical integration of clinical, biochemical, and experimental data on oxidative stress, mitochondrial dysfunction, Excitation-Contraction (E-C coupling) dysregulation, and muscle secretome alterations in ME/CFS also in relation to post-viral syndromes (e.g., Long COVID). Evidence consistently points to mitochondrial oxidative stress, redox imbalance, impaired Ca[2+] handling, and altered signaling pathways in skeletal muscle of patients with ME/CFS. Historical milestones show an evolution from psychogenic interpretations toward recognition of ME/CFS as a biological disorder with neuromuscular and metabolic underpinnings. ME/CFS can be interpreted as a skeletal muscle-metabolic disorder characterized by oxidative distress, mitochondrial dysfunction, and impaired energy regulation, leading to the clinical picture of exercise intolerance and post-exertional malaise. Integrating basic and clinical research through a translational approach provides the foundation for new diagnostic tools, targeted therapies, and biomarkers.},
}

@article {pmid41976810,
year = {2026},
author = {Barr, J and Marsden, L and Dassanayake, T and Almutairi, N and McKeever, V and Gaber, T and Tarrant, R and Godfrey, B and Witton, S and Sivan, M},
title = {Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Long COVID.},
journal = {Journal of clinical medicine},
volume = {15},
number = {7},
pages = {},
pmid = {41976810},
issn = {2077-0383},
support = {133038//The ME Association/ ; },
abstract = {Background/Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are complex multisystem conditions with significant functional disability. Many patients experience symptoms of orthostatic intolerance, which can be captured in some cases as Orthostatic Hypotension (OH) or Postural orthostatic Tachycardia Syndrome (PoTS) on objective testing. Conservative treatments are recommended for first-line symptom management, but there is a lack of efficacy evidence. This study aims to assess the feasibility of an 8-week clinically supervised, personalised Dysautonomia Management Protocol (DMP) in a cohort of ME/CFS and LC patients with subjective and objective evidence of orthostatic intolerance (dysautonomia). Methods: ME/CFS and LC patients with objective dysautonomia on the 10 min active Lean Test (LT) were recruited to an 8-week DMP, with interventions introduced cumulatively every two weeks. Interventions included increasing daily fluid intake to 3 litres and salt intake to 10 g, pacing to avoid crashes and calf activation. Baseline and weekly data collection included the LT, Composite Autonomic Symptom Score questionnaire (COMPASS-31) and Yorkshire Rehabilitation Scale (YRS). Results: Sixteen participants completed the 8-week program, five discontinued during the program, and one was withdrawn following a severe crash. The COMPASS-31 improved by 7.7 points from week 1 to week 8 (p = 0.045), with a medium Cohen's d effect size of 0.55. For the same period, there was a non-significant (p = 0.16) improvement in the YRS symptom severity score by 2 points. Comparing the final two weeks of the program with the first two weeks, mean heart rate during the LT decreased by 4.8 beats per minute (p = 0.032), with a medium Cohen's d effect size of 0.44. Adherence to the interventions was highly variable, with none of the patients able to fully employ all four recommendations. Conclusions: The results suggest that targeted conservative interventions could influence autonomic function and symptom reduction. However, the magnitude of change was limited, and statistical significance might not necessarily relate to a clinically significant improvement in symptoms.},
}

@article {pmid41976966,
year = {2026},
author = {Mihai, AM and Marc, M and Lucaciu, F and Sima, A},
title = {Incident Heart Failure Risk Following COVID-19 Recovery: A Systematic Review and Meta-Analysis.},
journal = {Journal of clinical medicine},
volume = {15},
number = {7},
pages = {},
pmid = {41976966},
issn = {2077-0383},
support = {We would like to acknowledge the Victor Babes University of Medicine and Pharmacy, Timisoara, for paying the APC. The funder had no role in study design, data collection/analysis, decision to publish, or manuscript preparation//Victor Babeș University of Medicine and Pharmacy Timișoara/ ; },
abstract = {Background/Objectives: While acute cardiac injury during COVID-19 is well-documented, the long-term risk of new-onset heart failure (HF) in survivors remains a critical clinical concern. This study aims to quantify the risk of new-onset heart failure during a 25 months prognostic follow-up period following recovery from SARS-CoV-2. Methods: We conducted a systematic review and meta-analysis of nine high-quality studies (n > 400,000 survivors) in accordance with PRISMA 2020 guidelines. Databases including PubMed/MEDLINE and Scopus were searched through January 2026. A quantitative meta-analysis was performed on six studies using a random-effects model to pool adjusted hazard ratios (aHR). Results: The pooled analysis revealed a significant 35% increased risk of new-onset heart failure following COVID-19 recovery (aHR 1.35; 95% CI: 1.14-1.60; p = 0.001). Significant heterogeneity was observed (I[2] = 92.62%), reflecting diverse risk profiles among survivors. The risk was most pronounced in immunocompromised kidney transplant recipients (aHR 2.32) and younger adults under the age of 65 (aHR 1.53). Subclinical myocardial damage, characterized by reduced left ventricular longitudinal strain, was identified even in survivors who experienced mild initial infections. Conclusions: COVID-19 recovery serves as a significant independent risk factor for chronic heart failure, emphasizing that cardiovascular impact extends far beyond the acute phase. These findings necessitate the implementation of structured cardiovascular monitoring and biomarker screening for at least one year post-infection to address this emerging chronic disease burden.},
}

@article {pmid41977143,
year = {2026},
author = {Jaishankar, S and Schaeper, D and Janga, SC and Srinivasan, M},
title = {Single-Cell Transcriptomic Analysis of Salivary Epithelial Cells Reveals Large-Scale Dysregulation in Bitter Taste Dysfunction.},
journal = {International journal of molecular sciences},
volume = {27},
number = {7},
pages = {},
doi = {10.3390/ijms27072953},
pmid = {41977143},
issn = {1422-0067},
support = {4476254//Delta Dental Research and Development Committee/ ; },
mesh = {Humans ; *Epithelial Cells/metabolism ; Single-Cell Analysis/methods ; *Saliva/cytology/metabolism ; Gene Expression Profiling ; *Transcriptome ; Female ; *COVID-19/complications/genetics ; Male ; *Taste/genetics ; Middle Aged ; *Dysgeusia/genetics/metabolism ; Adult ; Toll-Like Receptor 2/genetics/metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; Toll-Like Receptor 4/genetics/metabolism ; },
abstract = {Taste dysfunction, or dysgeusia, is a frequent symptom associated with infections and systemic diseases, yet its cellular and molecular basis remains poorly understood. The COVID-19 pandemic provided an opportunity to study dysgeusia as a "natural experiment" due to its high prevalence in those with acute and long COVID (LC). We investigated salivary epithelial cells (SECs) using single-cell RNA sequencing to elucidate molecular changes underlying taste dysfunction in LC. Functional enrichment analysis of SEC transcriptomes from individuals with bitter taste dysfunction (LC-D) revealed downregulation of genes involved in cytoskeletal dynamics and taste cell-nerve synapse assembly. Further, specific Type II and III taste receptor genes, critical for bitter taste perception, were reduced. Microbial defense markers such as Toll-like receptors TLR2 and TLR4 were also downregulated, suggesting chronic inflammation. These findings support a model of sustained dysregulated epithelial turnover due to impaired taste in LC-D. Saliva-based single-cell approaches offer promising tools for future diagnostics and mechanistic studies of taste systems.},
}

Humans
*Epithelial Cells/metabolism
Single-Cell Analysis/methods
*Saliva/cytology/metabolism
Gene Expression Profiling
*Transcriptome
Female
*COVID-19/complications/genetics
Male
*Taste/genetics
Middle Aged
*Dysgeusia/genetics/metabolism
Adult
Toll-Like Receptor 2/genetics/metabolism
Receptors, G-Protein-Coupled/genetics/metabolism
Toll-Like Receptor 4/genetics/metabolism

@article {pmid41978821,
year = {2026},
author = {Miller, DW and Rodgers-Melnick, SN and Deraz, NT and Dusek, JA and Segall, TL and Edwards, AM},
title = {Interdisciplinary Pediatric Long-COVID Care: A Descriptive Study of Interventions and Health-Related Quality of Life.},
journal = {Open forum infectious diseases},
volume = {13},
number = {4},
pages = {ofag155},
pmid = {41978821},
issn = {2328-8957},
abstract = {OBJECTIVES: Data on pediatric long-COVID is limited to descriptive reports of symptom prevalence and incidence, with few studies describing integrative care or including patient-reported quality of life. This study describes demographic, clinical, symptom severity, and intervention characteristics within a pediatric long-COVID clinic involving collaboration between infectious disease and integrative medicine physicians.

METHODS: Clinical data were extracted from the electronic health records for patients aged 4-25 with long-COVID seen within this clinic. A subset of patients completed validated PROs of wellbeing, fatigue, sleep-related impairment and disturbance, depression, and anxiety.

RESULTS: A cohort of 214 patients (mean age 14.7, 61% female, 83% White) were seen between March 2021 and June 2023, with 39.7% providing Pediatric Quality of Life Inventory (PedsQL) and 30.3% providing Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Common documented conditions included fatigue (85%), headache (75.2%), dizziness (64.5%), anxiety (62.1%), and nausea (59.3%). Common interventions included diet changes (81.8%), pacing (65.9%), sleep hygiene (61.2%), and other self-care techniques (46.7%). The long-COVID cohort reported elevated PROMIS sleep disturbance (61.79), sleep-related impairment (63.9), anxiety (58.1), and depression (58.1) as well as PedsQL total fatigue (40.19). These scores were more severe than national norms as well as compared with other pediatric chronic disease cohorts (eg, chronic pain, cancer, sickle cell disease, autism).

CONCLUSIONS: Pediatric patients with long-COVID report high symptom burden. This study describes patient characteristics, care delivered and provides a novel description of symptom severity. Future research among more diverse populations is needed to evaluate outcomes of this integrative care.},
}

@article {pmid41979136,
year = {2026},
author = {Kleeman, M and Nau, C and Su, J and Young, DR and Butler, R and Yang, LS and Batteate, C and Eng, S and Burnett, RT and Jerrett, M},
title = {Ambient Air Pollution and COVID-19 in California.},
journal = {Research report (Health Effects Institute)},
volume = {},
number = {238},
pages = {1-97},
pmid = {41979136},
issn = {1041-5505},
mesh = {Humans ; *COVID-19/epidemiology/mortality ; *Air Pollution/adverse effects/analysis/statistics & numerical data ; California/epidemiology ; Particulate Matter/analysis/adverse effects ; *Environmental Exposure/adverse effects ; Middle Aged ; *Air Pollutants/analysis/adverse effects ; SARS-CoV-2 ; Male ; Female ; Aged ; Adult ; Risk Factors ; Incidence ; },
abstract = {INTRODUCTION: As of December 2023, more than 6.9 million people globally had died from COVID-19, including more than 1.165 million deaths in the United States. It is estimated that approximately 18.8 million people in the United States have experienced post-acute COVID-19 conditions, also known as post-acute sequelae of SARS-CoV-2 (PASC) or long COVID, in the first 3 years after the pandemic. Although some initial cases of long COVID have resolved, with the ongoing incidence of COVID-19, roughly 17.8 million persons in the United States continue to suffer from long COVID at the time of this writing.[1-3] Preliminary evidence early in the COVID-19 pandemic suggested that exposure to air pollution increased the likelihood of contracting COVID-19 and worsened outcomes for those who became ill. The validity of these findings was uncertain, however, as few studies used highly accurate exposure models incorporating individual-level data on patient characteristics and risk factors. Although the COVID-19 public health emergency has ended, the disease continues to pose substantial risks to individual and population health. At the time of this writing, nearly 35,000 individuals per week are hospitalized with COVID-19 in the United States, and the weekly number of COVID-19-related deaths ranges from 900 to 1,400.[4].

METHODS: In this study, we investigated relationships between ambient air pollution and COVID-19-related outcomes, including incidence, severity, mortality, and long COVID conditions. We used advanced models to estimate exposures, incorporating numerous air pollutants, particle species, and wildfire emissions. We used administrative COVID-19 data and several cohorts of patients from a large health system, and each was formed to evaluate different hypotheses.

UNLABELLED: Daily air pollution exposures for Southern California were estimated with high spatial and chemical resolution, using a combination of land use regression and chemical transport models for the years 2016, 2019, and 2020. Exposure variables included ozone (O3), nitrogen dioxide (NO2), fine particulate matter (PM) ≤2.5 μm in aerodynamic diameter (PM2.5mass), ultrafine PM ≤0.1 μm in aerodynamic diameter (PM0.1), and major sources or chemical components of PM in each size fraction. Exposures for multiple study populations were investigated using statistical analysis methods to test for associations with COVID-19-related outcomes, including the following.

UNLABELLED: • COVID-19 cases (N = 773,374) and deaths (N = 14,311), by age, race, and sex, for 308 ZIP codes in Los Angeles County between June 19 and January 3, 2021. A negative binomial regression was performed for both individual and multiple ambient air pollutants to evaluate their associations with COVID-19 incidence and mortality.

UNLABELLED: • Patients with COVID-19 who were admitted to Kaiser Permanente Southern California (KPSC) hospitals between June 1, 2020, and January 30, 2021 (N = 21,415). Cox proportional hazards models were used to evaluate associations between ambient air pollutant exposure and COVID-19 mortality. A subset was of KPSC patients with COVID-19 who received care exclusively in KPSC hospitals (N = 15,978). A multistate survival model was used to examine how air pollution affects the transition to recovery or deterioration to more severe COVID-19 states (e.g., intensive care admission or death). A subset was of KPSC patients with COVID-19 who maintained membership with KPSC for 1 year after hospital discharge (N = 12,634). We combined a set of 45 diagnoses of post-acute sequelae of SARS-CoV-2 (PASC) into categories based on organ systems and then studied a subset of these PASC categories that could be affected by air pollution, including cardiac, cardiometabolic, pulmonary, and neurological conditions. Logistic regression was used to evaluate associations between 30-day air pollution exposure before hospital admission and PASC conditions diagnosed at 3 months and 12 months post-discharge.

RESULTS: PM0.1, O3, NO2, and PM2.5 elemental carbon exposures were identified as risk factors for COVID-19 incidence and mortality in the general population of Los Angeles County. Air pollution exposures were also significantly associated with COVID-19 mortality in the cohort of hospitalized KPSC patients, controlling for other individual health risks. Incremental increases equivalent to the interquartile range for several pollution exposure concentrations were significantly associated with increased mortality, including PM2.5 mass (hazard ratio [HR], 1.12), PM0.1(HR, 1.06), PM2.5 nitrate (HR, 1.12), PM2.5 elemental carbon (HR, 1.07), PM2.5 on-road diesel (HR, 1.06), and PM2.5 on-road gasoline (HR, 1.07). Humidity and temperature in the month of diagnosis were significant negative predictors of COVID-19 mortality and negative modifiers of the air pollution effects. Results of the multistate analysis were consistent with these findings and further suggested that O3, NO2, and PM2.5 each were associated with deteriorating health states. Increased PM2.5 concentration was associated with increased risk of deterioration to both intensive care admission (HR, 1.16) and death (HR = 1.11). Effects of O3 were similar to those of PM2.5, but O3 also affected the transition from recovery to death (HR, 1.24). Several air pollutants - particularly O3, PM0.1, and PM2.5 nitrate - were significantly associated with several long COVID outcomes, including cardiac, cardiometabolic, and pulmonary conditions.

CONCLUSIONS: Broadly, we concluded that several common air pollutants are associated with COVID-19 incidence, mortality, and progression to more severe states of illness, including long COVID conditions. Air pollution is a modifiable environmental risk factor that could be altered to improve the prognosis of COVID-19, thereby also reducing the public health impacts of coronaviruses now and in the future. This is particularly important for preventing long COVID, as evidence suggests that PASC conditions can occur even in vaccinated individuals. Given that 10% to 30% of individuals with COVID-19 will experience some form of PASC, which can have lifelong debilitating effects,[5] the importance of addressing modifiable environmental risk factors, such as air pollution, cannot be underestimated. A recent Lancet editorial noted that societal investment in understanding the pathogenesis of long COVID and preventive measures has lagged well behind the levels needed to effectively treat and mitigate this complex disease.[6] Our research focused mostly on hospitalized patients, but it also included one study on the general population effects. The results of both analyses were generally concordant, although our most important findings likely apply only to patients hospitalized with COVID-19.},
}

Humans
*COVID-19/epidemiology/mortality
*Air Pollution/adverse effects/analysis/statistics & numerical data
California/epidemiology
Particulate Matter/analysis/adverse effects
*Environmental Exposure/adverse effects
Middle Aged
*Air Pollutants/analysis/adverse effects
SARS-CoV-2
Male
Female
Aged
Adult
Risk Factors
Incidence

@article {pmid41979291,
year = {2026},
author = {Abid, S and Jannath, H},
title = {Cardiac Effects in Post-COVID-19 Heart Failure: A Systematic Review of Longitudinal Imaging- and Biomarker-Based Structural and Functional Remodeling.},
journal = {Annals of cardiac anaesthesia},
volume = {29},
number = {2},
pages = {157-168},
pmid = {41979291},
issn = {0974-5181},
mesh = {Humans ; *COVID-19/complications/diagnostic imaging/physiopathology ; Biomarkers/blood ; *Heart Failure/diagnostic imaging/physiopathology/etiology ; *Ventricular Remodeling/physiology ; Echocardiography ; Longitudinal Studies ; Magnetic Resonance Imaging ; },
abstract = {COVID-19 has been linked to persistent cardiovascular sequelae, yet the trajectory of structural and functional cardiac changes beyond the acute phase remains unclear. This systematic review synthesizes longitudinal evidence on post-COVID cardiac remodeling assessed by imaging and biomarkers. Following PRISMA guidelines, we searched PubMed and Cochrane Library (January 2020-April 2025) for peer-reviewed studies enrolling adults (≥18 years) with polymerase chain reaction (PCR)/antigen-confirmed SARS-CoV-2 infection and reporting cardiac outcomes ≥ 12 weeks post-infection. Eligible outcomes included imaging-based abnormalities (cardiac magnetic resonance [CMR]: T1/T2 mapping, late gadolinium enhancement [LGE]; echocardiography: left ventricular ejection fraction [LVEF], LV/RV strain). Longitudinal trends of biomarkers (troponin, NT-proBNP, C-reactive protein [CRP]) were also studied. Risk of bias was assessed using joanna briggs institute (JBI) tools; synthesis followed synthesis without metaanalysis (SWiM) principles. Fifteen studies (n ≈ 166,000; 14 cohorts, 1 case report) were included. Across CMR cohorts, global systolic function was largely preserved, but tissue abnormalities were frequent early and improved over time: edema indices normalized by ~ 12 months, while LGE prevalence declined (e.g. 50%→19% in paired scans). However, residual non-ischemic scars and elevated T1/T2 persisted in symptomatic subgroups. Echocardiography showed normal LVEF, but subtle left ventricular global longitudinal strain (LV-GLS) impairment versus controls (e.g. -18.5% vs - 19.3%). Biomarker trends were heterogeneous: natriuretic peptide positivity persisted in patients with prior cardiovascular disease (CVD), while troponin and CRP generally normalized. Large population-based cohorts demonstrated sustained 12-month risk for heart failure, myocarditis, and major cardiovascular events, graded by acute severity. Most patients recover gross systolic function, yet subclinical myocardial changes and elevated population-level cardiovascular risk persist up to 1 year. These findings support risk-stratified follow-up, judicious use of advanced imaging, and preventive cardiology strategies.},
}

Humans
*COVID-19/complications/diagnostic imaging/physiopathology
Biomarkers/blood
*Heart Failure/diagnostic imaging/physiopathology/etiology
*Ventricular Remodeling/physiology
Echocardiography
Longitudinal Studies
Magnetic Resonance Imaging

@article {pmid41969525,
year = {2026},
author = {Abdullah, M and Naz, A and Reznikov, LR and Qureshi, JA and Hasnain, A and Obaid, A and Ali, A},
title = {Neuropeptide and cytokines expression in long COVID-19 related neuropsychological sequelae: insights into NK1R-mediated neuroinflammation and in silico therapeutic targeting.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1763029},
pmid = {41969525},
issn = {1662-5102},
abstract = {BACKGROUND: Long COVID-19 causes neurophysiological, cardiopulmonary, and musculoskeletal issues. Increased neuropeptides and cytokines lead to neuroinflammation, resulting in neurocognitive impairments, fatigue, depression, anxiety, and severe cognitive deficits. The Neurokinin 1 receptor (NK1R) is a cellular receptor for the neuropeptide Substance P, and its dysregulation links to neuropsychological issues despite antipsychotic use.

OBJECTIVES: In the present study, neuropsychological sequelae related to long COVID-19 were screened and the expression of related neuropeptides and cytokines was evaluated. Additionally, potential drugs have been evaluated computationally to reduce neuroinflammation in long COVID-19.

METHODS: After informed consent, subjects were screened by a medical physician for long COVID-19 in an outdoor patient clinic. Various biological scales were used to assess and categorize the severity of neuropsychological symptoms related to long COVID-19. After that, peripheral blood samples were collected from subjects using ELISA and RT-qPCR. Nine drugs were selected and subjected to virtual screening to identify potential drug antagonists for NK1R. The key drug-like properties, safety profile, pharmacokinetic analysis, and biological activity of the identified hits were assessed.

RESULTS: In this study the mean age of 90 patients (60% males and 40% females), was 33 ± 5 years in the symptomatic group and 31 ± 6 years in the asymptomatic long COVID-19 group for <40 years age-group. Whereas, the mean age of >40 years age-group was 58 ± 10 years in the symptomatic group and 54 ± 11 years in the asymptomatic long COVID-19 group. The minimum persistence of duration of long COVID-19 related symptoms in the <30 weeks group was observed to be 19 ± 6 weeks, while 44 ± 6 weeks in the >30 weeks group of symptomatic long COVID-19. A total of 48% patients had fatigue, 47% complained about headache, 28% had anxiety, 25% faced depression, 20% had psychosocial distress, 20% felt discomfort, and 13% had cognitive impairment. A total of 10% had reported dizziness sequelae among long COVID-19 survivors. Experimental data showed upregulation of IL-6, IL-10, and SP in both symptomatic and asymptomatic individuals compared with controls (p < 0.001). Drug screening analyses revealed aprepitant (-9.3 kcal/mol) and N- acetyl- L- tryptophan (-8.7 kcal/mol) stable interactions with NK1R and maintaining molecular dynamics stability (RMSD: 1.5-2.2 Å; RMSF 0.8-1.4 Å; Rg approximately 21.6 Å). These compounds also demonstrated favorable blood-brain barrier permeability and pharmacokinetic profiles, suggesting their potential as therapeutic antagonists for treating prolonged COVID-related neuroinflammation.

CONCLUSION: IL-6, IL-10, and SP are found to be deregulated in long COVID-19 leading to neurophysiological sequelae. To overcome neuropsychological sequelae, binding of SP to NK1R can be hindered using aprepitant and N-Acetyl-L tryptophan which has been evaluated computationally and may require further in vivo and in vitro studies for validation.},
}

@article {pmid41969541,
year = {2023},
author = {Northstone, K and Suarez-Perez, A and Matthews, S and Crawford, M and Timpson, NJ},
title = {The Avon Longitudinal Study of Parents and Children - a resource for COVID-19 research: questionnaire data capture July 2021 to December 2021, with a focus on long COVID.},
journal = {Wellcome open research},
volume = {8},
number = {},
pages = {292},
doi = {10.12688/wellcomeopenres.19596.2},
pmid = {41969541},
issn = {2398-502X},
abstract = {ALSPAC, the Avon Longitudinal Study of Parents and Children is a prospective population-based cohort study. Pregnant women were recruited in 1990-1992 and the study has followed them, their partners (Generation 0; G0) and their offspring (Generation 1; G1) for over 30 years. During the coronavirus 2019 (COVID-19) pandemic, ALSPAC deployed a series of online questionnaires to capture participant experiences during this unprecedented time. In July 2021, a fifth questionnaire was deployed which primarily focussed on the symptoms of long COVID, also known as post-COVID syndrome. G0 and G1 participants were offered both online and paper questionnaires between 21 [st] July 2021 and 11 [th] December 2021. Of 21,138 invitations, 11,148 (52.8%) participants returned the questionnaire (4,763 original mothers [mean age 59.1 years], 2,074 original fathers/partners [mean age 62.0 years] and 4,311 offspring [mean age 29.0 years]). Of these 11,148 participants, 2835 (25.4%) had not completed any of the previous COVID-19 questionnaires, while 3480 (31.2%) had returned all four previous questionnaires. In this questionnaire, 1077 participants (9.8%) reported a previous positive COVID-19 test over the course of the pandemic. Of these, 109 (1.0%) had received medical advice that they likely had COVID-19, and 838 (7.6%) suspected that they had had COVID-19. Almost a third of participants (n=796, 31.1%) reported possible long COVID (experiencing symptoms for at least 4 weeks), whilst 351 (13.7%) reported symptom duration of 12 weeks or more (post-COVID syndrome). G0 mothers were more likely to report a longer duration of symptoms compared to their partners and their children. The fifth COVID-19 questionnaire deployed by ALSPAC and the data obtained from are described in this data note.},
}

@article {pmid41971233,
year = {2026},
author = {Adebisi, YA},
title = {Prepandemic Risk Factors for Disabling Long COVID: A Prospective Cohort Analysis.},
journal = {Journal of tropical medicine},
volume = {2026},
number = {},
pages = {9396282},
pmid = {41971233},
issn = {1687-9686},
abstract = {INTRODUCTION: Disabling long COVID, characterised by persistent symptoms that limit daily functioning, has emerged as an important public health concern. However, prospective evidence on predisposing risk factors remains limited.

METHODS: This study used prospective data from the UK Household Longitudinal Study, linking prepandemic baseline information collected in Wave 10 (2018-19) with follow-up data from Wave 14 (2022-23). The analytic sample comprised 12,033 adults aged ≥ 16 years who participated in both waves and self-reported a positive COVID-19 test at follow-up. The primary outcome, disabling long COVID, was defined as symptoms lasting more than 12 weeks that impaired day-to-day activities. Prepandemic sociodemographic, health and psychosocial factors assessed at baseline were included as predictors. Associations were estimated using modified Poisson regression with robust standard errors to calculate adjusted relative risks (RRs).

RESULTS: Disabling long COVID was reported by 690 individuals (5.7%). Higher risk was observed among women (RR 1.26; 95% CI 1.08-1.48) and adults aged 30-49 (RR 1.38; 95% CI 1.10-1.73) or 50-69 (RR 1.28; 95% CI 1.01-1.62) years, compared with those aged 16-29 years. Additional risk factors included pre-existing health conditions (RR 1.31; 95% CI 1.10-1.56), poor self-rated health (RR 1.78; 95% CI 1.40-2.25), psychological distress (RR 1.44; 95% CI 1.21-1.72) and poorer sleep quality (fairly bad: RR 1.92; 95% CI 1.45-2.56; very bad: RR 1.96; 95% CI 1.37-2.81), compared with very good sleep quality. Compared with non-White participants, White participants had lower risk (RR 0.75; 95% CI 0.61-0.92), while moderate (RR 0.76; 95% CI 0.62-0.93) and high (RR 0.81; 95% CI 0.67-0.98) income satisfaction, compared with low-income satisfaction, were protective. Stratified analyses showed that the effects of rural residence (p for interaction = 0.011) and income satisfaction (p = 0.009) differed significantly by sex, with weaker evidence for age (p = 0.095) and self-rated health (p = 0.061).

CONCLUSION: Prepandemic health, socioeconomic and psychological vulnerabilities were independently associated with disabling long COVID, with distinct sex-specific patterns of risk.},
}

@article {pmid41971988,
year = {2026},
author = {Ma, S and Koplin, E and Shilts, MH and Voehler, M and Rachakonda, G and Gil-Redondo, R and Rajagopala, SV and Sabaté Del Río, J and Botta-Orfila, T and Sibila, O and Asad, M and Sehanobish, E and Jerschow, E and Phillips, E and Millet, Ó and Mallal, SA and Das, SR},
title = {A quantitative metabolic signature of host response during SARS-CoV-2 infection and recovery.},
journal = {iScience},
volume = {29},
number = {4},
pages = {115390},
pmid = {41971988},
issn = {2589-0042},
abstract = {COVID-19 has individualized disease trajectories during both acute infection and long-term recovery ("long COVID"), highlighting the need for biomarkers for the disease's heterogeneity. In this study, we introduce "metabo-time," a quantitative metabolic signature derived from serum metabolites and lipoproteins measured via nuclear magnetic resonance (NMR) spectroscopy. Metabo-time was stablished across two longitudinal and demographically diverse cohorts and validated in independent populations. It captures patient-specific metabolic states throughout the disease course. Longitudinally, it is disrupted during acute infection and normalizes during recovery, mirroring systemic oxidative stress and immune response dynamics. Importantly, metabo-time outperforms actual recovery time in predicting patients' individualized normalization of oxidative stress. At baseline, it distinguishes infection severity and is associated with transcriptional activity in the upper airway. These findings establish metabo-time as a robust marker for tracking COVID-19 heterogeneity and progression, with potential utility for stratifying patients and informing therapeutic strategies, particularly in the context of SARS-CoV-2 recovery.},
}

@article {pmid41972671,
year = {2026},
author = {Asaba, CN and Gwanyama, BN and Ayuk, HS and Odo, TI and Bitazar, R and Noumi, T and Labonté, P and Bukong, TN},
title = {Neutrophil Extracellular Traps in Viral Infections: Regulation, Immune Consequences, and Pathogenic Outcomes.},
journal = {Cells},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/cells15070580},
pmid = {41972671},
issn = {2073-4409},
support = {Relance 2024//The INRS-Armand-Frappier Santé Biotechnologie Research Centre/ ; 363424//A doctoral scholarship from the Fonds de Recherche du Québec./ ; },
mesh = {*Extracellular Traps/immunology ; Humans ; *Neutrophils/immunology ; *Virus Diseases/immunology/pathology ; Animals ; COVID-19/immunology ; SARS-CoV-2/immunology ; Immunity, Innate ; Signal Transduction ; },
abstract = {Neutrophils are among the early responders of the innate immune system and play a key role in host defense against viral infections. Beyond their classical antimicrobial functions, neutrophils can engage in a specialized defense mechanism by releasing web-like extracellular DNA known as neutrophil extracellular traps (NETs). These extracellular traps are a mesh-like network of chromatin DNA decorated with cellular components, including histones, proteases, and antimicrobial enzymes, that function to contain and limit the spread of pathogens. While NET formation contributes to antiviral immunity, accumulating evidence indicates that excessive or dysregulated NET formation can significantly contribute to immunopathology during viral infections. Thus, depending on the context and outcome, NET formation may be viewed as a double-edged sword. Therefore, understanding the regulatory mechanisms governing NET formation and its harmful effects is critical for developing therapeutic strategies that enhance antiviral defense while minimizing tissue damage. In this review, we provide a comprehensive overview of the molecular mechanisms that drive NET formation and clearance, with a particular focus on how viruses modulate these processes to influence disease outcome. We also discuss the pathways underlying NET formation and subsequent neutrophil cell death (NETosis), including canonical and non-canonical pathways, and highlight key signaling axes involving SYK, MAPKs, and NF-κB. Using SARS-CoV-2 and hepatitis B virus as representative models, we examine how different viral components trigger, exploit, or evade NET targeting and how persistent accumulation of NETs can contribute to hyperinflammation, progressive tissue injury, and post-viral syndromes. We further explore emerging evidence linking impaired NET clearance and neutrophil heterogeneity, particularly low-density neutrophils (LDNs), to chronic inflammation and post-viral sequelae such as long COVID and autoimmune hepatitis. Finally, we summarize current and emerging therapeutic strategies aimed at modulating NET formation or enhancing NET clearance. Altogether, this review underscores the dual nature of NETs in viral infections, highlighting their potential roles in antiviral defense and tissue injury, and provides a framework for the development of targeted interventions to limit virus-induced immunopathology.},
}

*Extracellular Traps/immunology
Humans
*Neutrophils/immunology
*Virus Diseases/immunology/pathology
Animals
COVID-19/immunology
SARS-CoV-2/immunology
Immunity, Innate
Signal Transduction

@article {pmid41973314,
year = {2026},
author = {Peddireddy, S and VanWingerden, N and Patel, P and Howard, G and Berger, J},
title = {Stellate Ganglion Block in the Treatment of Long COVID: A Systematic Review.},
journal = {Current pain and headache reports},
volume = {30},
number = {1},
pages = {},
pmid = {41973314},
issn = {1534-3081},
mesh = {Humans ; *Stellate Ganglion ; *COVID-19/complications/therapy ; *Autonomic Nerve Block/methods ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVES: This review evaluates stellate ganglion block as a treatment for long COVID, seeking to evaluate the treatment's efficacy by various symptoms and the limitations of the current literature.

STUDY DESIGN: Systematic Review.

SETTING: Ambulatory or Outpatient Setting.

METHODS, SUBJECTS: A systematic review of the current literature regarding use of stellate ganglion block in patients with long COVID was conducted. 2 databases were searched on August 28th, 2025. Search terms were "long COVID" and "stellate ganglion block", yielding 45 results. Studies examining patient outcomes after stellate ganglion block were included. Case reports, case series, basic science studies and previous reviews were excluded. Seven studies met inclusion criteria.

RESULTS: Patients received a single stellate ganglion block in some studies and multiple stellate ganglion blocks in others. All studies reported symptomatic improvement without control groups. Response rates ranged from 55.8% to 100%. The most robust improvements (> 80% patients reporting relief) were seen in cough, dyspnea, headache, joint pain, pain interference/intensity, pins/needles, subjective relief.

CONCLUSION: Stellate ganglion block is a promising treatment that appears to generate substantive benefit for many of the symptoms seen in long COVID. However, the current literature has small, uncontrolled studies with heterogenous study designs and follow-up periods. Standardized research with larger sample sizes, control groups, and longer-term follow up is necessary to elucidate the degree of benefit. IRB approval and clinical trial registration not required.},
}

Humans
*Stellate Ganglion
*COVID-19/complications/therapy
*Autonomic Nerve Block/methods
Treatment Outcome
Post-Acute COVID-19 Syndrome

@article {pmid41973786,
year = {2026},
author = {O'Loughlin, KM and Herring, TE and Gentile, NL and Bender, JA and Friedly, JL and Knowles, LM},
title = {Correlates of patient interest in rehabilitation psychology services among individuals with long COVID: A cross-sectional analysis.},
journal = {Rehabilitation psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/rep0000671},
pmid = {41973786},
issn = {1939-1544},
support = {/HS/AHRQ HHS/United States ; },
abstract = {PURPOSE/OBJECTIVE: Long COVID is a complex chronic condition, affecting approximately 18% of adults in the United States and commonly involves fatigue, cognitive impairment, pain, and psychiatric conditions (e.g., depression, anxiety, posttraumatic stress disorder, and insomnia). Despite high psychiatric burden, many individuals do not receive mental health care, and little is known about their interest in psychological services. This study characterized symptom profiles of long COVID and examined correlates of patients' interest in rehabilitation psychology services.

RESEARCH METHOD/DESIGN: Secondary data analysis of routinely collected clinical data. Descriptive statistics were calculated, and logistic regression analyses examined associations of interest.

RESULTS: Participants in the full sample (N = 1,789) were predominantly White, non-Hispanic, and female, with high rates of fatigue (84.9%), cognitive difficulties (55.3%-74.3%), and psychiatric history (51.8%). Over half (56.8%) expressed interest in rehabilitation psychology services, including individual (50.2%) and group (32.1%) formats. Two participants were excluded from regression analyses due to sparse cell size, yielding a final analytic sample of n = 1,787. Interest in individual services was associated with not having a mental health provider, greater depression and anxiety, poor sleep, and lower cognitive functioning. Interest in group services was associated with psychiatric history, greater anxiety, lower cognitive and social functioning, and better physical functioning.

CONCLUSION/IMPLICATIONS: Anxiety symptoms and cognitive difficulties are key correlates of interest in rehabilitation psychology services, underscoring the value of early screening and targeted intervention. Stigma and prioritization of medical concerns may limit engagement, highlighting the importance of psychoeducation and stigma-reduction efforts to support engagement in care. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid41975034,
year = {2026},
author = {Matthews, R and Alam, A and Bullmore, E and Michael, BD},
title = {Understanding the long-term neurological effects of SARS-CoV-2 infection.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {41975034},
issn = {1759-4766},
abstract = {Post-COVID-19 condition (PCC), also known as long COVID, is a heterogeneous condition marked by persistent symptoms following acute SARS-CoV-2 infection. As approximately 6% of people who have experienced acute COVID-19 are estimated to develop PCC, the potential population is vast. Many of the key symptoms of PCC reflect involvement of the nervous system, ranging from cognitive impairment ('brain fog'), headaches and fatigue to anxiety and depression. This Review summarizes the spectrum of neurological and psychological symptoms that occur following acute SARS-CoV-2 infection, with a particular focus on the international consensus-based core outcome set for PCC. We also explore the proposed underlying mechanisms, including evidence for immune system dysregulation, microvascular dysfunction and volumetric changes on neuroimaging. In addition, we review ongoing and completed large-scale treatment trials. Growing evidence suggests a bidirectional interaction between symptoms traditionally considered neurobiological in origin, such as cognitive deficits and headache, and those within the purview of psychiatry, such as anxiety and depression. PCC represents an opportunity to better understand the long-term consequences of acute infection and improve management strategies and outcomes, not only for people with the condition but also for those with other post-viral syndromes that affect brain health.},
}

@article {pmid41975235,
year = {2026},
author = {Bansal, A and Olechnowicz, SWZ and Kiernan-Walker, N and Cumming, J and Abdul Azeez, I and Mazhari, R and , and Cox, RJ and Mueller, I and Bowden, R and Eriksson, EM},
title = {Divergent inflammatory and neurology-related protein levels in long COVID following primary and breakthrough SARS-CoV-2 infections.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01541-6},
pmid = {41975235},
issn = {2730-664X},
abstract = {BACKGROUND: Long COVID is a complex condition where symptoms persist for more than 3 months after SARS-CoV-2 infection and affects an estimated 5-30% of individuals. While persistent inflammation has emerged as an important feature of this condition, it is unclear if immune responses from COVID-19 vaccination or SARS-CoV-2 re-infection exacerbate or mirror the initial inflammatory responses.

METHODS: We quantified 182 inflammatory and neurology-related proteins in plasma using multiplexed affinity proteomics. Plasma samples from the COVID PROFILE cohort conducted in Victoria, Australia, were collected 6-9 months after first infection, but before COVID-19 vaccination from individuals who had recovered from COVID-19 (n = 21) or from individuals with long COVID (n = 12). To establish baseline plasma profiles, protein levels were benchmarked against unvaccinated, SARS-CoV-2 naive individuals (n = 24). In addition, we performed longitudinal analysis in a subset of individuals (n = 34), where paired samples collected 2-4 weeks after a third COVID-19 vaccine dose and after SARS-CoV-2 breakthrough infection were available to assess inflammatory and neurology protein plasma levels after antigen exposure in these contexts.

RESULTS: In this cohort Boruta feature selection and lasso regression models identified IL-20, HAGH, NAAA, CLEC10A, LXN, and MCP-1, TRAIL, G-CSF, NBL1, and CCL23 as best discriminating proteins when comparing the long COVID group to groups of either healthy or COVID-19 recovered. Notably, longitudinal analysis indicated differences in the levels of a subset of plasma proteins following primary infection compared to after COVID-19 booster vaccination and breakthrough infection within the groups.

CONCLUSIONS: These findings suggest that there is an altered immune response outcome primarily observed in individuals with long COVID upon re-exposure.},
}

@article {pmid41965722,
year = {2026},
author = {Magnúsdóttir, I and Nygaard, AB and Hoffart, A and Murphy, G and Kõiv, K and Barker, MM and Lovik, A and Unnarsdóttir, AB and Kähler, AK and Hauksdóttir, A and Thordardottir, EB and Eyþórsson, E and Gísladóttir, EU and Joyce, EE and Frans, EM and Tómasson, G and Hjördísar Jónsdóttir, HL and Rúnarsdóttir, H and Harðardóttir, H and Dahl, JA and Jakobsdóttir, J and Kalleberg, KT and Ásbjörnsdóttir, KH and Ellingjord-Dale, M and Istre, MS and Landrø, NI and Shen, Q and Bø, R and Mägi, R and Pálsson, R and Brunvoll, SH and Johnson, SU and Søraas, A and Fang, F and Lehto, K and Ebrahimi, OV and Aspelund, T and Valdimarsdóttir, UA},
title = {Acute COVID-19 severity and impaired cognitive function up to 32 months after diagnosis: an observational study.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04856-2},
pmid = {41965722},
issn = {1741-7015},
support = {2022-00597//Forskningsrådet för hälsa, arbetsliv och välfärd/ ; PSG615//Eesti Teadusagentuur/ ; 138929//NordForsk/ ; 847776//Horizon 2020/ ; },
abstract = {BACKGROUND: Cognitive dysfunction ("brain fog") is a commonly reported post-COVID-19 symptom. Leveraging data from five general population cohorts across four European countries (Estonia, Iceland, Norway, and Sweden), we assessed long-term prevalence of impaired subjective cognitive function among individuals diagnosed with COVID-19 by acute illness severity.

METHODS: The included cohorts consisted of adult participants recruited from March 2020 and followed with self-report measures of cognitive function and past COVID-19 infection (except one cohort consisting of clinically confirmed COVID-19 cases) through February 2023. In a cross-sectional analysis we contrasted the prevalence of impaired cognitive function among individuals with and without a COVID-19 diagnosis, overall and by illness severity up to 32 months post-diagnosis. We adjusted for age, gender, education, relationship status, binge drinking, body mass index, previous psychiatric diagnosis, number of chronic medical conditions, and response period. In a longitudinal analysis, we assessed potential changes in cognitive function scores before and after COVID-19 diagnosis.

RESULTS: The study population consisted of 153,841 participants (71% women), with 31,359 (20.4%) reporting a positive COVID-19 test. Overall, a COVID-19 diagnosis was not statistically significantly associated with increased prevalence ratio (PR) of impaired cognitive function (PR 1.30 [95% CI: 0.98-1.71]). Individuals bedridden due to COVID-19 for 1-6 days (PR 1.38 [95% CI 0.96-1.99]) or ≥ 7 days (2.59 [1.55-4.33]) had higher prevalence of impaired cognitive function compared to those never diagnosed, while individuals never bedridden had a lower prevalence to those never diagnosed with COVID-19 (0.89 [0.80-1.00]). These findings were corroborated in the longitudinal analysis where a pre- to post diagnosis decline in cognitive function was observed among individuals bedridden due to COVID-19 (p < 0.0001).

CONCLUSIONS: The data indicates that a severe COVID-19 acute illness course is associated with impaired cognitive function up to 18-32 months after COVID-19 diagnosis.},
}

@article {pmid41965729,
year = {2026},
author = {Springe, ML and Vaivode, K and Saksis, R and Vainšeļbauma, NM and Ansone, L and Brīvība, M and Niedra, H and Rovite, V},
title = {Immune dysregulation in prolonged Long-COVID: lymphocytes emerge as key mediators of persistent inflammation, exhaustion and cytotoxicity.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08081-6},
pmid = {41965729},
issn = {1479-5876},
abstract = {BACKGROUND: Long-COVID affects at least 10% of COVID-19 survivors, displaying debilitating symptoms across multiple organ systems. Despite the widespread prevalence, Long-COVID aetiology remains poorly understood, but emerging evidence points to immune dysregulation as a potential mechanism involved in its development or persistence.

METHODS: This study presents a unique analysis of the peripheral blood mononuclear cell transcriptomic profile of COVID-19 and Long-COVID patients at single-cell resolution. We reconstructed the cell state and intercellular communication using differentially expressed gene profiling and ligand-receptor interaction analyses.

RESULTS: Our results reveal altered T and natural killer cell subset proportions, diminished proliferating lymphocyte and B cell signalling capacity, and the expression of exhaustion and cytotoxicity associated genes 1.5-2 years post-infection, suggesting incomplete immune recovery. Distinct interferon responses in these cell populations at the acute phase for patients who go on to develop Long-COVID indicate early disease mediator potential.

CONCLUSIONS: Collectively, these findings provide insight into the immune processes underlying the progression of COVID-19 into a chronic Long-COVID state. The observed changes in immune cell subsets at the acute phase of the infection may be predictive of Long-COVID progression and could be useful in understanding disease aetiology while the observed long-term effects are crucial to developing therapeutic and diagnostic tools.},
}

@article {pmid41966515,
year = {2026},
author = {Gardiner, LE and Lozano-Rojas, D and Smith, N and Espley, J and Stewart, ID and Ntotsis, K and Aul, R and Bakerly, ND and Beirne, P and Bolton, CE and Brown, JS and Briggs, A and Chalder, T and Chalmers, JD and Choudhury, G and Davies, MJ and De Soyza, A and Docherty, AB and Easom, N and Echevarria, C and Efstathiou, CM and Elneima, O and Fuld, J and Geddes, JR and Goemans, AF and Greenhalf, W and Greening, NJ and Guillen-Guio, B and Harris, VC and Harrison, EM and Hart, N and Heaney, LG and Heller, S and Ho, LP and Horsley, A and Houchen-Wolloff, L and Howard, L and Hurst, JR and Iqbal, MM and Jacob, J and Jenkins, RG and Jolley, C and Jones, M and Kerr, S and Khunti, K and Leavy, OC and Lewis, K and Lone, NI and Lord, JM and Man, WD and Marks, M and McAuley, HJC and McCann, GP and Neubauer, S and Openshaw, PJ and Parekh, D and Pfeffer, P and Poinasamy, K and Porter, JC and Quint, JK and Rahman, NM and Raman, B and Richardson, M and Rowland-Jones, SD and Rowland, MJ and Saunders, RM and Scott, JT and Semple, MG and Sereno, M and Shah, AM and Sheikh, A and Shikotra, A and Singapuri, A and Taquet, M and Thomas, D and Thompson, AAR and Thorpe, M and Toshner, M and Wang, L and Wootton, DG and Zheng, B and Wain, LV and Brightling, CE and Singh, SJ and Taylor, RS and Evans, RA and , },
title = {Investigating prognostic classifications of pre-existing multiple long-term conditions for health outcomes one-year after COVID-19 hospitalisation: a UK prospective observational study.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108695},
doi = {10.1016/j.ijid.2026.108695},
pmid = {41966515},
issn = {1878-3511},
abstract = {BACKGROUND: Pre-existing multiple (two or more) long-term conditions (MLTCs) may negatively affect recovery after COVID-19. We investigated how pre-existing MLTCs, including different categorisation and patterns of MLTCs, affect one-year health outcomes after severe COVID-19.

METHODS: Adults post-hospitalisation following COVID-19 were recruited during 2020 -2021. We compared recovery at one-year after discharge using adjusted multivariable logistic regression in 1:1 propensity matched adults (for age, sex, ethnicity, social deprivation, obesity, and smoking history) with and without pre-existing MLTCs. In adults with MLTCs, different categorisation such as number of conditions, number and types of body systems involved (e.g., respiratory, cardiovascular), and latent class analysis derived patterns of condition co-occurrence were assessed for their association with recovery at one-year.

FINDINGS: 647 adults with MLTCs were matched with 647 adults without MLTCs (n=1294; 61.9% male, 79.6% of white ethnicity, median age 59 [IQR 52-67] years). The presence of MLTCs were associated with lower odds of feeling fully recovered (odds ratio (OR) 0.66 [95% CI 0.51 to 0.85], p=0.001). In those with MLTCs, recovery was negatively affected by number and type of body systems involved (e.g., respiratory (OR 0.49 [95% CI 0.34 to 0.69], p<0.001)) but not by the number of conditions (p>0.1). Four latent classes of MLTCs co-occurrence were estimated with different risks of recovery (p<0.01).

INTERPRETATION: Adults with pre-existing MLTCs were 34% less likely to feel fully recovered at one-year after COVID-19 hospitalisation compared with adults without MLTCs. We describe prognostic classifications of MLTCs with future work needed to understand if they have prognostication in broader post-acute infection sequalae.},
}

@article {pmid41966782,
year = {2026},
author = {Shi, H and Zhang, Y and Yao, Z and Song, W and Xu, X and Tang, X and Cui, L and Song, H and Shu, R and Wang, J and You, X},
title = {Aminopeptides ameliorate long COVID symptoms in immunocompromised rheumatic patients through immune reconstitution.},
journal = {International immunopharmacology},
volume = {179},
number = {},
pages = {116630},
doi = {10.1016/j.intimp.2026.116630},
pmid = {41966782},
issn = {1878-1705},
abstract = {OBJECTIVE: To evaluate the effects of aminopeptide nutritional support on immune reconstitution and antiviral capacity in immunocompromised patients with rheumatic diseases.

METHODS: This single-center, retrospective cohort study included patients with rheumatic diseases and concomitant immunocompromised conditions who received treatments at the outpatient department of Peking Union Medical College Hospital between December 2021 and October 2024. Participants were divided into an experimental group (aminopeptide supplementation) and a control group according to whether they received aminopeptide treatment, with a treatment duration of 2-3 months. Data regarding SARS-CoV-2 virus infection, specific Long COVID symptoms, and outcomes were collected via questionnaire. TB lymphocyte subsets were recorded before and after treatment or at 3-6-month intervals.

RESULTS: A total of 171 patients with rheumatic diseases were enrolled, including 102 in the experimental group and 69 in the control group. Eighty-eight patients exhibited Long COVID symptoms, with fatigue being the most prevalent (67%). The experimental group showed a significantly higher rate of Long COVID symptom remission compared to the control group (64.2% vs. 22.9%), with a notable improvement in fatigue (68.3% vs. 27.8). Significant post-treatment increases were observed in peripheral blood CD3[+] T cells and CD8[+] T cells. Multivariate logistic regression analysis indicated that aminopeptide supplementation increased the rate of Long COVID symptom remission by 8.46-fold and the rate of fatigue improvement by 9.19-fold.

CONCLUSION: Supplementation with aminopeptides may improve nutritional status and enhance TB lymphocyte subsets levels in immunocompromised patients with rheumatic diseases, potentially contributing to better antiviral immunity and alleviation of Long COVID symptoms.},
}

@article {pmid41967005,
year = {2026},
author = {Iskander, JK and Haridopolos, S},
title = {Making Invisible Illnesses Visible: Recognizing and Responding to Infection Associated Chronic Conditions.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciag240},
pmid = {41967005},
issn = {1537-6591},
abstract = {The emergence of post-COVID conditions (PCC) has renewed attention to infection-associated chronic conditions and illnesses (IACCI), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Lyme disease-associated chronic symptoms. Millions of Americans are affected by these debilitating, misunderstood conditions, which share symptom profiles and pathophysiologic abnormalities. IACCI have received insufficient clinical attention and research investment. We outline elements of a patient-centered approach to care, emphasizing validation of patients' experiences, multidisciplinary management, and symptom-focused treatment. Opportunities to strengthen clinical practice include a new CMS code for chronic condition management, extended visits, and creation of welcoming care environments. Advances in PCC and ME/CFS research provide a foundation for exploring shared mechanisms and developing targeted therapies. Improved surveillance, harmonized research, and inclusive trial designs are needed to define disease burden and accelerate therapeutic progress. Coordinated action by clinicians, researchers, and policymakers can help address longstanding gaps and improve outcomes for all individuals with IACCI.},
}

@article {pmid41964305,
year = {2026},
author = {Rosemberg, MS and Park, S},
title = {Covid Is Gone but Not Fully: Addressing Long Covid Among Workers.},
journal = {Workplace health & safety},
volume = {},
number = {},
pages = {21650799261434057},
doi = {10.1177/21650799261434057},
pmid = {41964305},
issn = {2165-0969},
}

@article {pmid41958356,
year = {2026},
author = {Bohlin, J and Lee, Y and Caspersen, IH and Hayman Robertson, A and Page, CM and Gjessing, HK and Jugessur, A and Magnus, P and Mjaaland, S and Trogstad, L},
title = {Longitudinal study of genome-wide DNA methylation in individuals with and without post-acute symptoms following SARS-CoV-2 infection.},
journal = {Epigenomics},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/17501911.2026.2656361},
pmid = {41958356},
issn = {1750-192X},
abstract = {BACKGROUND: Symptoms following SARS-CoV-2 infection, referred to as Long-COVID, have been reported since the pandemic. We investigated whether COVID-19 or Long-COVID is associated with persistent genome-wide DNA methylation (DNAm) changes in whole blood using a longitudinal design.

METHODS: DNAm was measured using the Illumina EPIC V2 platform (859,651 CpGs) in 297 adult participants (594 samples in total) from two Norwegian population-based cohorts, with samples collected pre-infection (2020) and during the pandemic (2023). Participants were classified as Long-COVID, COVID-19 (no persistent symptoms), or not infected.

RESULTS: No significant DNAm differences were observed between Long-COVID and not infected at either time point (p = 0.745(FDR)) or during the pandemic specifically (p = 0.629(FDR)). Likewise, no differences were detected between COVID-19 and not infected across both time points (p = 0.883(FDR)) or during the pandemic (p = 0.287(FDR)). Sex-stratified analyses of the X chromosome revealed no significant DNAm differences for Long-COVID or COVID-19 in males (both p = 0.999(FDR)) or females (both p = 0.999(FDR)). Epigenetic age acceleration was also evaluated using DunedinPACE (DP) and PhenoAge (PA), but no significant differences were detected for Long-COVID (p = 0.695 [DP], p = 0.528 [PA]) or COVID-19 (p = 0.624 [DP], p = 0.348 [PA]).

CONCLUSION: No persistent epigenetic age- or DNAm based differences due to Long-COVID or SARS-CoV-2 infection were detected in our cohorts.},
}

@article {pmid41959563,
year = {2026},
author = {Waters, M and Vlok, M and Kroon, EE and Kotze, MJ and Moremi, KE and Oladejo, SO and Rajaratnam, K and Nunes, JM and Venter, C and Scott, CJ and Kell, DB and Pretorius, E},
title = {Proteomic signatures of COVID-19 Post-Vaccination/Post-Infection Syndrome (PV/PIS): insights into immune dysregulation and coagulopathy.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1753348},
pmid = {41959563},
issn = {2235-2988},
mesh = {Humans ; *COVID-19/immunology/blood ; Proteomics ; Male ; *COVID-19 Vaccines/adverse effects ; Middle Aged ; Female ; SARS-CoV-2/immunology ; *Vaccination/adverse effects ; Adult ; Aged ; *Blood Coagulation Disorders/etiology ; *Proteome/analysis ; Chromatography, Liquid ; Post-Infectious Disorders ; },
abstract = {INTRODUCTION: During the global rollout of COVID-19 vaccines, a subset of individuals reported persistent symptoms following vaccination, with clinical presentations overlapping those of Long COVID and requiring individualised treatment strategies. Distinguishing between vaccine-related adverse events and post-infectious sequelae is challenging, particularly given the potential for unrecognised asymptomatic or mild SARS-CoV-2 infection before or after vaccination. To address this complexity, we defined our disease cohort as individuals experiencing persistent symptoms (≥ 12 weeks) following SARS-CoV-2 vaccination, without a confirmed history of prolonged symptoms after acute infection; for clarity, we refer to this group as presenting with Post-Vaccination/Post-Infection Syndrome (PV/PIS).

METHODS: In this study, we conducted a plasma proteomic analysis of digested microclot deposits isolated from platelet-poor plasma samples of 14 individuals with PV/PIS compared to 16 healthy controls, using liquid-chromatography-mass spectrometry.

RESULTS: We identified significant alterations in coagulation factors, acute phase proteins, and immune response modulators in the PV/PIS group compared to controls. Notably, elevated levels of serum amyloid A1 and A2, attractin, and coagulation factors X and XI were observed, alongside downregulation of immune-regulatory proteins. These findings suggest that PV/PIS is characterised by persistent immune dysregulation and coagulopathy.

CONCLUSIONS: This proteomic signature was found to only partially overlap with that previously reported in a proteomics analysis on Long COVID samples, collected prior to vaccination availability. Our results highlight the complex interplay between immune activation, endothelial dysfunction, and coagulation pathologies in PV/PIS, with distinct differences detected between these systems in Long COVID and PV/PIS, paving the way for more targeted protein research in these conditions.},
}

Humans
*COVID-19/immunology/blood
Proteomics
Male
*COVID-19 Vaccines/adverse effects
Middle Aged
Female
SARS-CoV-2/immunology
*Vaccination/adverse effects
Adult
Aged
*Blood Coagulation Disorders/etiology
*Proteome/analysis
Chromatography, Liquid
Post-Infectious Disorders

@article {pmid41960594,
year = {2026},
author = {Leverty, R and Sutton, S and Jackson, C and Cerda, M and Chang, A and Zimmerman, K},
title = {Engaging patients and researchers in RECOVER clinical trial protocol development: Key lessons.},
journal = {Journal of clinical and translational science},
volume = {10},
number = {1},
pages = {e49},
pmid = {41960594},
issn = {2059-8661},
abstract = {The RECOVER Clinical Trials Protocol Working Groups (PWGs) were established to rapidly design trials addressing Long COVID by incorporating the complementary expertise of researchers, clinicians, and patients, caregivers, and community representatives (Representatives). This paper explores the engagement of Representatives in protocol development, highlighting their contributions, challenges faced, and lessons learned. A survey of PWG members revealed that while most Representatives felt their input was valued, gaps in role clarity, communication, and integration of feedback persisted. Representatives emphasized the importance of understanding patient burden and lived experience, while researchers and project leaders noted the value of inclusive perspectives. Findings underscore the need for structured engagement practices, clear expectations, and ongoing support to ensure meaningful participation. These insights offer a roadmap for future clinical trial networks seeking to integrate patient voices in research design.},
}

@article {pmid41962975,
year = {2026},
author = {Dai, Y and Luo, H and Liu, X and Hu, BM and Wang, M and Cheng, LX and Luo, Y and Ma, XY and Cao, G and Mao, Q and Li, L},
title = {Health outcomes and reinfection among COVID-19 survivors 4 years after hospital discharge in Wuhan, China: a cohort study.},
journal = {BMJ open},
volume = {16},
number = {4},
pages = {e113446},
doi = {10.1136/bmjopen-2025-113446},
pmid = {41962975},
issn = {2044-6055},
mesh = {Humans ; Male ; *COVID-19/epidemiology/complications ; Middle Aged ; China/epidemiology ; Female ; Longitudinal Studies ; Risk Factors ; Patient Discharge ; Aged ; *Reinfection/epidemiology ; SARS-CoV-2 ; Fatigue/epidemiology ; *Survivors/statistics & numerical data ; Adult ; Anxiety ; Depression/epidemiology ; },
abstract = {OBJECTIVES: To evaluate health outcomes and identify risk factors for reinfection and persistent symptoms among COVID-19 survivors 4 years after hospital discharge.

DESIGN: Longitudinal cohort study.

SETTING: Two hospitals in Wuhan, China.

PARTICIPANTS: 1076 COVID-19 survivors discharged from hospital.

OUTCOME MEASURES: Self-reported symptom questionnaire, Chronic Obstructive Pulmonary Disease Assessment Test, Hospital Anxiety and Depression Scale and Checklist Individual Strength (CIS) fatigue subscale. Long covid was defined according to WHO criteria.

RESULTS: Median age was 58 years and 50.2% were male. Reinfection during December 2022-April 2023 occurred in 36.1%; 21 developed pneumonia and 14 required hospitalisation. At least 12 months after reinfection, 12.1% reported sequelae compared with 46.9% after the initial infection. At 4 years, 16.7% reported long covid symptoms, commonly fatigue, chest tightness, cough and dyspnoea. In multivariable analysis, risk factors for abnormal fatigue (CIS ≥27) included age (OR 1.020, 95% CI 1.007 to 1.034; p=0.003), reinfection (OR 2.393, 95% CI 1.708 to 3.352; p<0.001), severe disease (OR 1.553, 95% CI 1.088 to 2.218; p=0.015) and tumour (OR 3.420, 95% CI 1.177 to 9.936; p=0.024).

CONCLUSIONS: At 4 years post discharge, symptom burden was lower than at earlier follow-up time points for most survivors. Reinfection and older age were associated with persistent symptoms.},
}

Humans
Male
*COVID-19/epidemiology/complications
Middle Aged
China/epidemiology
Female
Longitudinal Studies
Risk Factors
Patient Discharge
Aged
*Reinfection/epidemiology
SARS-CoV-2
Fatigue/epidemiology
*Survivors/statistics & numerical data
Adult
Anxiety
Depression/epidemiology

@article {pmid41952397,
year = {2026},
author = {Mavroudis, P and Ragia, G and Pantazis, N and Dermitzaki, E and Stamati, A and Pallikarou, M and Velentza, L and Paflioti, E and Zarkotou, O and Gerakari, S and Giannitsioti, E and Gravanis, A and Manolopoulos, VG},
title = {Association of ADIPOQ rs1501299 with long-COVID syndrome: a single-center cross-sectional study.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2654244},
doi = {10.1080/07853890.2026.2654244},
pmid = {41952397},
issn = {1365-2060},
mesh = {Humans ; *Adiponectin/genetics/blood ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; Polymorphism, Single Nucleotide ; *COVID-19/genetics/complications/blood ; Adult ; SARS-CoV-2 ; Aged ; Genetic Predisposition to Disease ; Genotype ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long-COVID syndrome is a public health issue, affecting millions of individuals worldwide. However, the pathophysiological mechanisms underlying the syndrome's sequelae are still under investigation. Adiponectin has been implicated with acute SARS-CoV2 infection, while its role in Long-COVID remains obscure. The aim of this study is to investigate the potential association of adiponectin and SNPs of adiponectin pathway with Long-COVID.

MATERIALS AND METHODS: A single-center cross-sectional observational study was conducted, investigating the potential association of adiponectin and SNPs of adiponectin pathway with Long-COVID in 159 individuals, who were presented at the COVID-19 outpatient re-evaluation office. Adiponectin blood levels and detection of SNPs ADIPOQ rs1501299, ADIPOQ rs2241766, ADIPOR2 rs16928751, PPARA rs1800206 and PPARG rs1801282 were measured 3 months after acute COVID-19.

RESULTS: ADIPOQ rs1501299 was the only SNP significantly associated with the progression of symptoms after the acute SARS-CoV2 infection and the development of Long-COVID syndrome. Homozygous GG genotype individuals exhibited increased risk for sequelae of Long-COVID (OR 2.0, 95% CI 1.1, 3.7, p = 0.023), particularly fatigue (OR 2.4, 95% CI 1.2, 5.0, p = 0.014), compared to the T allele carriers, independently of age, sex, BMI, waist to hip ratio, comorbidities and severity of acute infection (OR 2.2, 95% CI 1.2, 4.3, p = 0.013 and OR 3.1, 95% CI 1.4, 6.7, p = 0.004 respectively). Adiponectin levels were correlated with obesity and severity of acute SARS-CoV2 infection, but not with Long-COVID symptoms.

CONCLUSION: ADIPOQ rs1501299 could potentially serve as a genetic marker, contributing to risk stratification of developing Long-COVID syndrome.},
}

Humans
*Adiponectin/genetics/blood
Cross-Sectional Studies
Male
Female
Middle Aged
Polymorphism, Single Nucleotide
*COVID-19/genetics/complications/blood
Adult
SARS-CoV-2
Aged
Genetic Predisposition to Disease
Genotype
Post-Acute COVID-19 Syndrome

@article {pmid41953516,
year = {2026},
author = {Qu, HQ and Kao, C and Hakonarson, H},
title = {Redefining the role of the thiol-based agent N-acetylcysteine in human health and disease and elucidating potential advantages of its amide derivative.},
journal = {RSC medicinal chemistry},
volume = {},
number = {},
pages = {},
pmid = {41953516},
issn = {2632-8682},
abstract = {N-Acetylcysteine (NAC) is the established antidote for acetaminophen toxicity and an approved mucolytic agent. Beyond these traditional uses, increasing evidence highlights its broader role as a modulator of thiol-redox biology. Rather than functioning as a nonspecific antioxidant, NAC modulates glutathione metabolism, redox-sensitive signaling, immune checkpoints, thiol-based post-translational modifications, ferroptosis susceptibility, and glutamatergic neurotransmission. This review synthesizes mechanistic, preclinical, and clinical evidence across pulmonary, hepatic, neuropsychiatric, metabolic, cardiovascular, and oncologic disorders, emphasizing how variability in baseline redox state, pharmacogenetics, and delivery contributes to heterogeneous outcomes. Strategies to improve pharmacokinetics and tissue targeting include structural derivatives such as N-acetylcysteine amide (NACA), and combination regimens such as NAC with probenecid or GlyNAC. Emerging applications span long COVID, neurodegeneration, psychiatric disorders, microbiome-redox interactions, environmental toxicology, and cancer immunotherapy. NAC and NACA exemplify the evolution of redox-targeted therapeutics. NAC is well established for safety and clinical utility, but its pharmacokinetic and tissue distribution properties constrain broader efficacy. NACA, a lipophilic amide derivative, enhances membrane permeability and cellular uptake, suggesting it may achieve higher tissue exposure at lower doses. Future progress will rely on biomarker-guided, precision approaches that optimize dosing, formulation, and delivery while exploring rational combinations across disease contexts defined by redox biology.},
}

@article {pmid41955274,
year = {2026},
author = {Wu, D and Dasgupta, A and Hora, JS and Chen, KH and Banerjee, A and Archer, SL},
title = {SARS-CoV-2 targets mitochondria, exacerbating COVID-19 pneumonia.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP290297},
pmid = {41955274},
issn = {1469-7793},
support = {SEA-20-015//Southeastern Ontario Academic Medical Organization/ ; MM1181122/CAPMC/CIHR/Canada ; },
abstract = {Mitochondrial damage is a conserved feature of coronavirus infection, occurring with human (SARS-CoV-2, HCoV-OC43) and murine (MHV-1) coronaviruses. Coronaviruses damage mitochondria in airway epithelial cells (AEC), pulmonary artery smooth muscle cells (PASMC), pulmonary artery endothelial cells, immune cells and cardiomyocytes by causing rapid transcriptomic changes in nuclear-encoded genes regulating mitochondria and by viral proteins interacting with host mitochondrial proteins. Coronavirus infection causes mitochondrial depolarization, mitochondrial transition pore (MTP) opening, inhibition of the electron transport chain (ETC) and ATP synthetic apparatus, increased mitochondrial fission, apoptosis, and impaired mitochondrial oxygen sensing. Within hours of infection, SARS-CoV-2 induces transcriptional reprogramming of genes relevant to the mitochondrial matrix in AECs, downregulating mRNA encoding ETC complex I components and the ATP synthesis complex. These bioenergetic consequences of SARS-CoV-2 mitochondriopathy may contribute to long COVID. Infection also upregulates dynamin-related protein 1 (DRP1), activating mitochondrial fission while promoting apoptosis by activating apoptosis inducing factor (AIF) and caspase 7. Even without infection, transfection with specific coronaviral proteins opens the MTP and depolarizes the mitochondria, or activates DRP1 and AIF, promoting AEC damage or apoptosis, thereby contributing to diffuse alveolar damage. In human PASMCs, coronaviral M and Nsp9 proteins suppress hypoxic pulmonary vasoconstriction (HPV), a homeostatic mechanism in PASMCs that uses a mitochondrial oxygen sensor to redistribute blood flow to well-ventilated lung regions during pneumonia. Impairment of HPV, seen as intrapulmonary shunting, contributes to the profound hypoxaemia in COVID-19 pneumonia. Coronavirus-induced mitochondriopathy may have therapeutic relevance as blocking AIF-induced apoptosis or enhancing HPV appears beneficial in a MHV-1 model of COVID-19 pneumonia.},
}

@article {pmid41947189,
year = {2026},
author = {Zhou, L and Sun, Y and Yang, R and Zhao, Q and Xiao, M},
title = {Latent profile analysis of the symptoms for posttraumatic stress disorder and psychological resilience in Chinese adolescents experiencing post Covid-19: a quantetative study.},
journal = {BMC psychology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40359-026-03987-8},
pmid = {41947189},
issn = {2050-7283},
support = {2024CQ059//Humanities and Social Science Fund of Ministry of Education of China/ ; JY20240202//Chongqing Medical University/ ; CYYY-DSTDXM-202409//The First Affiliated Hospital of Chongqing Medical University/ ; },
}

@article {pmid41951239,
year = {2026},
author = {Casassus, B},
title = {Long covid's £8bn bill: OECD report warns pandemic continues to cast a "long shadow".},
journal = {BMJ (Clinical research ed.)},
volume = {393},
number = {},
pages = {s662},
doi = {10.1136/bmj.s662},
pmid = {41951239},
issn = {1756-1833},
}

@article {pmid41951431,
year = {2026},
author = {Tamariz, L and Rozenfeld, I and Iglesias, R and Bast, E and Avecillas, S and Shehadeh, L and Klimas, N and Palacio, A},
title = {Dysautonomia in Long COVID is Prevalent and Could Explain the Frequency of Symptoms.},
journal = {Clinical medicine & research},
volume = {24},
number = {1},
pages = {28-34},
doi = {10.3121/cmr.2025.2054},
pmid = {41951431},
issn = {1554-6179},
mesh = {Humans ; Female ; Male ; Middle Aged ; *COVID-19/complications/epidemiology/physiopathology ; *Primary Dysautonomias/epidemiology/physiopathology/diagnosis ; Cross-Sectional Studies ; Prevalence ; Heart Rate ; Aged ; Adult ; SARS-CoV-2 ; Blood Pressure ; },
abstract = {Background: Long COVID presents with a variety of symptoms, some of which could be related to autonomic dysfunction. Our aim was to evaluate the prevalence of autonomic dysfunction in long COVID patients.Methods: We conducted a cross-sectional study and included all consecutive patients enrolled in several clinical research studies. We performed the following autonomic dysfunction markers: heart rate variability, heart rate, systolic and diastolic blood pressure changes during NASA Lean Test, cardiopulmonary exercise testing and a Composite-Autonomic-Symptom-Score (COMPASS)-31 scale. We used linear regression to calculate the contribution of each dysautonomia measure on symptom burden as measured by the modified COVID-19 Yorkshire scale.Results: We included 100 patients for this study. Our sample population had a mean age of 56+/-11 years, included 53% minorities, and 32% were women. Dysautonomia, as defined by an abnormal COMPASS-31, was seen in 82% (95% confidence interval [CI] 72-89) of our study population, while cardiovascular resting dysautonomia, as represented by an abnormal heart rate variability, was seen in 60% (95% CI 48-70) of our study population. Orthostatic hypotension was observed in 12% of our study population, and postural orthostatic tachycardia syndrome (POTS) was found in 10% of our study population. In our adjusted analysis, we found that the beta coefficient for the COMPASS-31 score (0.37) was significant on changes in a self-reported long COVID symptom burden. The orthostatic intolerance and gastrointestinal domains of the COMPASS-31 were associated with the highest long COVID symptom burden.Conclusion: Dysautonomia is common in long COVID patients and contributes to the overall symptoms seen in long COVID. Identifying dysautonomia has important diagnostic and therapeutic implications.},
}

Humans
Female
Male
Middle Aged
*COVID-19/complications/epidemiology/physiopathology
*Primary Dysautonomias/epidemiology/physiopathology/diagnosis
Cross-Sectional Studies
Prevalence
Heart Rate
Aged
Adult
SARS-CoV-2
Blood Pressure

@article {pmid41951954,
year = {2026},
author = {King, R and Ford, T and Coleman, Z and Hammond, E and Henley, D and Hirschtick, JL},
title = {Racial Disparities in Long COVID: Why Black Americans are Likely Underrepresented in Long COVID Estimates.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {41951954},
issn = {2196-8837},
}

@article {pmid41943185,
year = {2026},
author = {Maziero, MP and Lee, EA and Colpo, GD and Couture, L and Merrill, LC and Baskin, L and Cahuiche, AE and Petway, A and Fan, H and Reese, E and Anderson, KM and McCullough, LD and Schulz, PE and Ortiz, GJ},
title = {Cognitive Trajectories After Hospitalization for COVID-19: A 36-Month Longitudinal Study.},
journal = {The Journal of neuropsychiatry and clinical neurosciences},
volume = {},
number = {},
pages = {appineuropsych20250267},
doi = {10.1176/appi.neuropsych.20250267},
pmid = {41943185},
issn = {1545-7222},
abstract = {OBJECTIVE: Neurological symptoms are commonly reported among individuals with postacute sequelae of COVID-19 (PASC), with cognitive impairment being the most common feature, but cognitive trajectories in PASC have not been clearly defined. The authors determined long-term cognitive changes in a cohort of individuals hospitalized with COVID-19, characterized their distinct cognitive trajectories, and identified factors associated with each trajectory at 36 months posthospitalization.

METHODS: The sample comprised 630 patients who were hospitalized with severe COVID-19 symptoms; 214 patients returned for at least one follow-up assessment over a 36-month period. Cognitive function, including attention, cognitive flexibility, processing speed, and memory, was evaluated by using BrainCheck, a validated digital platform, at 3-6, 12, 24, and 36 months posthospitalization. Longitudinal changes in cognitive performance and their associations with demographic factors, medical history, and neuropsychiatric symptoms were analyzed with linear mixed-effects models.

RESULTS: Four distinct cognitive trajectories over 36 months were identified and characterized. Group 1 (N=103, 48%) exhibited consistent normal cognitive function, group 2 (N=14, 7%) transitioned from unimpaired to impaired, group 3 (N=29, 14%) changed from impaired to unimpaired, and group 4 (N=68, 32%) showed persistent impairment across all domains. Poorer cognitive outcomes were associated with Hispanic ethnicity, although effects varied across domains.

CONCLUSIONS: As with many viral encephalitides, some patients showed stable normal or abnormal cognition or improved cognition over time. Surprisingly, however, a fourth subset exhibited delayed cognitive decline. This observation suggests that PASC-associated mechanisms, perhaps including chronic cerebral inflammation, may cause progressive cognitive impairment well after the initial infection clears.},
}

@article {pmid41944489,
year = {2026},
author = {Jóźwiak, A and Lewandowska, A and Sawicka, D and Jędrzejewska, A and Braczko, A and Romanowska-Kocejko, M and Żarczyńska-Buchowiecka, M and Deptuła, M and Zawrzykraj, M and Pikuła, M and Kutryb-Zając, B and Hellmann, M and Mierzejewska, P},
title = {Post-COVID increase in N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY) associates with inflammatory and endothelial activation markers.},
journal = {Nucleosides, nucleotides & nucleic acids},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/15257770.2026.2650677},
pmid = {41944489},
issn = {1532-2335},
abstract = {COVID-19 is associated with long-term vascular complications, but the underlying mechanisms remain incompletely understood. During infection, NAD[+] homeostasis becomes dys-regulated, with excessive NAD[+] consumption and enhanced catabolic flux through nicotinamide methylation pathways. This imbalance leads to NAD[+] depletion accompanied by accumulation of pyridone metabolites, including N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone-3-carboxamide (Met4PY). These derivatives have been linked to oxidative stress, endothelial dysfunction, and cardiovascular risk, yet their role in long COVID remains unclear. We enrolled 26 post-COVID patients with persistent cardiovascular symptoms and 8 healthy controls. Serum concentrations of Met2PY and Met4PY were quantified by LC/MS. High-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNFα), interleukin-10 (IL-10), and soluble intercellular adhesion molecule-1 (sICAM-1) were measured to assess systemic inflammation and endothelial activation. Statistical analyses included group comparisons and correlation analyses. We observed significantly elevated Met2PY levels (0.770 ± 0.08 vs. 0.389 ± 0.09 µmol/l) and a trend toward increased Met4PY (0.095 ± 0.01 vs. 0.055 ± 0.01 µmol/l) in post-COVID patients compared with controls. Both metabolites positively correlated with hsCRP. Importantly, Met2PY was associated with an unfavorable cytokine profile (higher TNFα/IL-10 ratio) and increased sICAM-1 levels, whereas no such associations were observed for Met4PY. Persistent dysregulation of NAD[+] metabolism and accumulation of pyridone metabolites, particularly Met2PY, are associated with markers of chronic endothelial activation and inflammation in long COVID. These findings support the potential utility of Met2PY as a biomarker to identify patients at higher risk for endothelial dysfunction and cardiovascular events, enabling more personalized risk stratification and follow-up.},
}