Animal models of post-acute COVID-19 syndrome: a call for longitudinal animal studies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 26, 2025

Animal models are indispensable for unraveling the mechanisms underlying post-acute sequelae of COVID-19 (PASC). This review evaluates recent research on PASC-related perturbations in animal models, drawing comparisons with clinical findings. Despite limited number studies post-COVID conditions, particularly those extending beyond three months, these provide valuable insights. Three hallmark features PASC-lung fibrosis, hyperglycemia, and neurological sequelae-have been successfully replicated paving way mechanistic discoveries future medical interventions. Although most have reported conditions within 14-60 days post-infection, they still offer critical reference long-term research. also explores potential persisting immune misfiring, a key factor chronicity PASC symptoms. Moreover, challenges modeling discussed, including genetic diversity inbred strains difficulties accurately identifying PASC-affected individuals. To address issues, we propose methodological improvements, such as comparing individual parameters control averages incorporating genetically diverse populations like collaborative cross models. These strategies will enhance identification characterization endotypes studies. By integrating findings from manifestations PASC, can more insights into its support development effective therapeutic strategies. Finally, emphasize urgent need longitudinal to fully uncover driving guide interventions mitigate public health impact.

Language: Английский

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Comparison of Phenotypes of Headaches After COVID-19 Vaccinations Differentiated According to the Vaccine Used

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 113 - 113

Published: Jan. 23, 2025

Background/Objectives: In this ongoing, multicenter, global cohort observational study, phenotypes of headaches after COVID-19 vaccination were directly compared between different vaccines. Methods: Phenotypes postvaccinal headache recorded in 18,544 participants. The study was launched immediately the start campaign on 12 January 2021 and continued until 1 August 2023. Specific aspects related variables collected via an online questionnaire. clinical characteristics patients vaccinated with Comirnaty (BioNTech), Jcovden (Johnson & Johnson), Sputnik V (Gamelaya), Covilo (Sinopharm), Spikevax (Moderna), Vaxzevria (AstraZeneca), Convidecia (CanSino Biologics) vaccines investigated. Results: Across all vaccines, median mean latency onset vaccine administration h 23.3 h, respectively. duration When nonreplicating viral vector used, occurred fastest, a 17 h. latencies for 14.9 19.1 inactivated whole-virus had 20.5 mRNA-based 26.0 22.02 Analysis variance revealed no significant differences tested. Compared Comirnaty, Covilo, induced significantly greater intensities. associated higher frequency concomitant symptoms than other Conclusions: phenotype can vary These results have implications differentiating primary secondary headaches. This knowledge is clinically relevant life-threatening complications, such as thrombotic syndromes, which are also Based these results, new diagnostic criteria be developed.

Language: Английский

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Editorial: NeuroCOVID. Insights into the clinical manifestations and pathophysiology

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 11, 2025

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome 2 (SARS-CoV-2), led to a global pandemic that placed the world in worst health situation of last century. It is known cause multi-organ dysfunction during acute phase and some patients experience prolonged symptoms. In both instances nervous system has been reported be affected. Neurological complications were identified for first time 36.4% hospitalized Wuhan (1). From then on, subsequent different variants COVID 19 with varying frequency neurological have appeared, rendering comparisons between subtypes difficult. For example, Delta variant enhance susceptibility develop ischemic stroke, epilepsy, seizures, cognitive impairments infected individuals (2).Furthermore, not all studies analyze manifestations same manner. Some consider signs symptoms, others focus mainly on disorders combine symptoms diseases. These can roughly divided into two categories - those occurring infection, generally associated direct invasion central or peripheral tissues virus due severe systemic neuroinflammatory responses (cytokine storm), post-viral (3).This editorial approaches analysis 8 articles published Research Topic, which are focused COVID-19 post-acute manifestations, extends broader general NeuroCOVID imposes research purposes public policies (4).The high COVID-19, especially patients; although from included this Topic it possible estimate incidence, because only adult who developed new-onset hospitalization included. Hanganu et al evaluated 115 patients, reporting (CNS) more frequent than involvement (PNS), they independently older age, disease severity, heart disease, increased D-dimers. COVID-19-associated encephalopathy was most common CNS manifestation, but neurovascular events also important. On other hand, Mazraeh al. clinical describing wide range include such as headaches, dizziness, altered mental state, disorientation, well PNS involving impairment taste smell, musculoskeletal issues. children acquire very life-threatening revealed Zhang 4 necrotizing after infection Omicron BF.7.14 coronavirus, had previously described variants. Previously, rare delayed hyperinflammatory response SARS-CoV-2 (multisystem inflammatory syndrome) children, prevalent Alpha (2).Focusing PNS, Yu centered their investigation how significantly incidence severity facial nerve paralysis (PFNP) throughout years. similar basis, Tereshko explored 30 previous SARS-CoV2 normal sensory conduction studies, 3 months disease. Employing Semmes–Weinstein monofilament test, demonstrated impaired tactile sensation A-beta fibers, suggesting post-COVID subclinical damage fibers. The prevalence brain consequence SARS does seem related specifically infection. According neuropathological findings Humayun al, overall injury non-COVID-19 SARS, specific etiology lung injury. underlying culprits inflammation hypoxemia, taking part an inexorably damaging brain-lung crosstalk. We should keep mind mild respiratory like cough dyspnea, worsen leading cytokine storm, significant damage, frequently requiring intensive care. Early therapeutic interventions, including non-invasive ventilation methods, recommended prevent hypoxemia curb progression storm (5).Two engaged performance, post-COVID-19. Hotz showed notable deficits domain attention. treatment strategies inconclusive spontaneous remission could excluded. Chaganti observed loss white matter integrity, possibly mediated blood-brain barrier breakdown glutamatergic excitotoxicity at months, improved 12 months. Summarizing, may lead variety covering spectrum extend relatively (headache, myalgia, smell impairment) serious (stroke, venous sinus thrombosis, encephalomyelitis Guillain Barre syndrome, among others. Almost five years cases detected, field neuro-COVID still its early stages much yet learned about long-term effects system. Many exhibit complex long-lasting fog, corresponding long brain, manifest psychological functional (confusion, fatigue, short-term memory loss, distraction reduced acuity), impair daily life activities. Very recently condition accumulation persistent viral spike protein skull, meninges together sustained inflammation, complete clearance (6). Furthermore, trigger exacerbate neurodegeneration Parkinson' s Alzheimer Multiple Sclerosis (3).These opening new avenues optimize prevention, diagnostic tools targeting neurologic COVID-19. As pass, investigators gaining knowledge pathophysiology This challenging issue great number affected world.

Language: Английский

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Magnetoencephalography Reveals Neuroprotective Effects of COVID-19 Vaccination in Non-Human Primates

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

COVID-19, caused by the SARS-CoV-2 virus, can lead to widespread neurological complications, including cognitive deficits and neurodegenerative symptoms, even in absence of significant structural brain abnormalities. The potential neuroprotective effects vaccination remain underexplored. Here, we demonstrate a psoralen-inactivated vaccine non-human primate model using resting-state magnetoencephalography (MEG), non-invasive neurophysiological recording technique with sub-millisecond temporal submillimeter spatial resolution. MEG scans demonstrated substantial preservation neural activity across multiple regions vaccinated subjects compared unvaccinated controls following viral challenge. This approach not only underscores role mitigating severe outcomes but also highlights capability detect subtle yet changes function that may be overlooked other imaging modalities. These findings advance our understanding vaccine-induced neuroprotection establish as powerful tool for monitoring context infections.

Language: Английский

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Neuroinflammation: An Oligodendrocentric View

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Chronic neuroinflammation, driven by central nervous system (CNS)-resident astrocytes and microglia, as well infiltration of the peripheral immune system, is an important pathologic mechanism across a range neurologic diseases. For decades, research focused almost exclusively on how neuroinflammation impacted neuronal function; however, there accumulating evidence that injury to oligodendrocyte lineage component for both clinical outcomes. While oligodendrocytes are able undergo endogenous repair process known remyelination, this becomes inefficient usually fails in presence sustained inflammation. The present review focuses our current knowledge regarding activation innate adaptive systems chronic demyelinating disease, multiple sclerosis, provides other conditions, such perinatal white matter injury, traumatic brain viral infections, converges injury. Lastly, therapeutic potential targeting impact inflammation these diseases discussed.

Language: Английский

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Impact of SARS-CoV-2 Variants and Vaccination on Pediatric Febrile Seizures: A Retrospective Cohort Study

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Objective This study aimed to investigate the associations between SARS-CoV-2 variants, neuroinflammatory markers, vaccination history, and demographic characteristics in relation occurrence of febrile seizures (FS) pediatric patients at a single tertiary medical center. Methods Retrospective cohort data were collected from care institution April 2020 January 2023, encompassing 339 with PCR-confirmed infections. The was separated into FS (n=102) control (n=237) groups. A multivariable logistic regression analysis employed evaluate impact viral variants (Delta Omicron sublineages), inflammatory markers (IL-6, D-dimer, CRP), status (unvaccinated, partially vaccinated, fully vaccinated), variables, while controlling for potential confounders. Results incidence among infants under one year age found be 41.2%, contrast 17.7% older children (OR=3.2, 95% CI: 1.8–5.7; P<0.001). Elevated levels IL-6 exceeding 10 pg/mL D-dimer surpassing 0.5 mg/L independently associated increased severity (adjusted OR [aOR]=2.8 2.1, respectively), as well 3.1-fold increase risk recurrence. Full linked 68% reduction (aOR=0.32, 0.18–0.55), particularly benefiting infants. Additionally, male exhibited 1.8-fold vulnerability (P=0.016). sublineages (BA.5/XBB), which accounted 78.4% cases, correlated heightened biomarker levels. Conclusion findings suggest that serve valuable indicators assessing infected SARS-CoV-2. protective effect on neural tissues, addition its role reducing transmission, is evident, highlighting susceptibility

Language: Английский

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Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids

Exploration of neuroscience, Journal Year: 2025, Volume and Issue: 4

Published: March 24, 2025

The SAR-CoV-2 virus has evolved to co-exist with human hosts, albeit at a substantial energetic cost resulting in post-infection neurological manifestations [Neuro-post-acute sequelae of SARS-CoV-2 infection (PASC)] that significantly impact public health and economic productivity on global scale. One the main molecular mechanisms responsible for development Neuro-PASC, individuals all ages, is formation inadequate proteolysis/clearance phase-separated amyloid crystalline aggregates—a hallmark feature aging-related neurodegenerative disorders. Amyloidogenesis during viral persistence natural, inevitable, protective defense response exacerbated by SARS-CoV-2. Acting as chemical catalyst, accelerates hydrophobic collapse heterogeneous nucleation amorphous amyloids into stable β-sheet aggregates. clearance aggregates most effective slow wave sleep, when high levels adenosine triphosphate (ATP)—a biphasic modulator biomolecular condensates—and melatonin are available solubilize removal. dysregulation mitochondrial dynamics SARS-CoV-2, particular fusion fission homeostasis, impairs proper distinct subpopulations can remedy challenges created diversion substrates away from oxidative phosphorylation towards glycolysis support replication maintenance. subsequent reduction ATP inhibition synthesis sleep results incomplete brain aggregates, leading commonly associated age-related Exogenous not only prevents dysfunction but also elevates production, effectively augmenting solubilizing effect moiety ensure timely, optimal disaggregation pathogenic prevention attenuation Neuro-PASC.

Language: Английский

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Changes in cerebrovascular reactivity within functional networks in older adults with long-COVID

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Introduction Cognitive symptoms are reported in the vast majority of individuals with long-COVID and there is growing support to suggest neurovascular mechanisms may play a role. Older adults at increased risk for developing complications associated COVID-19, including heightened cognitive decline. Cerebrovascular Reactivity (CVR), marker health, has been linked age related decline role long-COVID, however, this not yet explored. Methods The present study examined group differences CVR 31 older compared cognitively unimpaired without symptoms. Follow up analyses were conducted examine how was both subjective neuropsychological (NP) test performance. A subject-specific approach, Distribution-Corrected Z-scores (DisCo-Z), used. Results Analyses revealed demonstrated significantly greater incidence extreme clusters within brain (&gt;100 voxels) functional networks thought drive attention executive function. Extreme positive positively number negatively correlated NP Discussion These findings among first provide link between functioning changes relevant aging mechanistic studies long-COVID.

Language: Английский

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AL5E: A breakthrough in broad-spectrum coronavirus inactivation through structure-guided design

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111221 - 111221

Published: April 1, 2025

Language: Английский

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Unraveling the SARS-CoV-2 spike protein long-term effect on neuro-PASC

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Dec. 18, 2024

The persistence or emergence of long-term symptoms following resolution primary SARS-CoV-2 infection is referred to as long COVID post-acute sequelae COVID-19 (PASC). PASC predominantly affects the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Among these, central nervous system (CNS) significantly impacted, leading a spectrum symptoms, including fatigue, headaches, brain fog, cognitive impairment, anosmia, hypogeusia, neuropsychiatric peripheral neuropathy (neuro-PASC). However, risk factors pathogenic mechanisms responsible for neuro-PASC remain unclear. This review hypothesis discusses hypotheses regarding pathophysiological involved in COVID/PASC, focusing on neuro-PASC. We propose vascular dysfunction mediated by activation astrocytes pericytes followed blood-brain barrier (BBB) disruption underlying neurological manifestations. Additionally, we provide insights into role spike protein at interface. Finally, explore potential initiated interaction between cellular receptors endothelial tissue levels.

Language: Английский

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