Nature Aging, Journal Year: 2024, Volume and Issue: 4(11), P. 1598 - 1618
Published: Nov. 14, 2024
Language: Английский
Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14
Published: Nov. 23, 2023
The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation retained for later like BA.5 and XBB remains controversial. We show that isolates were significantly more pathogenic in K18-hACE2 mice than a isolate, showing increased neurotropic potential, resulting fulminant brain infection mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains mice, neurons main target infection, neuronal progenitor cells immature infected. results herein suggest evolving may have increasing potential.
Language: Английский
Citations
25
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Feb. 29, 2024
Abstract Post-COVID-19 syndrome is a serious complication following SARS-CoV-2 infection, characterized primarily by fatigue and cognitive complaints. Although first metabolic structural imaging alterations in have been identified, their functional consequences remain unknown. Thus, we explored the impact of on connectome brain providing deeper understanding pathophysiological mechanisms. In cross-sectional observational study, resting-state magnetic resonance data 66 patients with after mild infection (mean age 42.3 years, 57 female) healthy controls 42.1 38 mean time seven months acute COVID-19 were analysed using graph theoretical approach. Network features quantified measures including distance, nodal degree, betweenness Katz centrality, compared between both groups. Graph correlated clinical quantifying fatigue, function, affective symptoms sleep disturbances. Alterations mainly found brainstem, olfactory cortex, cingulate thalamus cerebellum average infection. Additionally, strong correlations severity, functioning daytime sleepiness from scales observed. Our study confirms relevance changes as mediating factors for persistent improves our understanding.
Language: Английский
Citations
12
Heliyon, Journal Year: 2024, Volume and Issue: 10(4), P. e26577 - e26577
Published: Feb. 1, 2024
A critical step in the drug design for SARS-CoV-2 is to discover its molecular targets. This study comprehensively reviewed mechanisms of SARS-CoV-2, exploring host cell tropism and interaction targets crucial entry. The findings revealed that beyond ACE2 as primary entry receptor, alternative receptors, co-receptors, several proteases such TMPRSS2, Furin, Cathepsin L, ADAM play roles virus subsequent pathogenesis. Additionally, displays various human organs due diverse receptors. review delves into intricate details proteases, involvement each organ. Polymorphisms receptor mutations spike or RBD region contribute emergence variants like Alpha, Beta, Gamma, Delta, Omicron, impacting pathogenicity SARS-CoV-2. challenge posed by raises questions about effectiveness existing vaccines drugs, necessitating consideration updates their formulations. In urgency these situations, repurposed drugs Camostat Mesylate Nafamostat emerge viable pharmaceutical options. Numerous are involved inhibiting receptors factors entry, with most discussed this review. conclusion, may provide valuable insights inform decisions therapeutic approaches.
Language: Английский
Citations
8
Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(1)
Published: Jan. 1, 2024
Abstract Although the COVID‐19 pandemic has officially ended, persistent challenge of long‐COVID or post‐acute COVID sequelae (PASC) continues to impact societies globally, highlighting urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly long‐COVID/PASC research. This exhibits human expression in tissue cell‐specific patterns akin Ace2. When we exposed young adult hACE2ki mice (6 weeks old) various SARS‐CoV‐2 lineages, including WA, Delta, Omicron, at dose 5 × 10 PFU/mouse via nasal instillation, demonstrated distinctive phenotypes characterized by differences viral load lung, trachea, turbinate, weight loss, changes pro‐inflammatory cytokines immune cell profiles bronchoalveolar lavage fluid. Notably, no mortality was observed this age group. Further, assess model's relevance studies, investigated tau protein pathologies, which are linked Alzheimer's disease, brains these post infection. findings revealed accumulation longitudinal propagation tau, confirming potential our preclinical studies long‐COVID.
Language: Английский
Citations
8
Neuropathology and Applied Neurobiology, Journal Year: 2024, Volume and Issue: 50(2)
Published: Feb. 28, 2024
Olfactory dysfunction is one of the most common symptoms COVID-19. In first 2 years pandemic, it was frequently reported, although its incidence has significantly decreased with emergence Omicron variant, which since become dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory an ongoing health concern. The proposed pathogenic mechanisms are complex likely multifactorial. While evidence suggests that infection sustentacular cells associated mucosal inflammation may be culprit acute, transient smell loss, alterations in other components system (e.g., receptor neuron dysfunction, bulb injury cortex) lead persistent, long-term dysfunction. This review aims provide a comprehensive summary epidemiology, clinical manifestations current understanding
Language: Английский
Citations
7
Current Opinion in Microbiology, Journal Year: 2024, Volume and Issue: 79, P. 102474 - 102474
Published: April 13, 2024
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019, contributes to neurological pathologies in nearly 30% patients, extending beyond symptoms. These manifestations encompass disorders both peripheral and central nervous systems, causing among others cerebrovascular issues psychiatric during and/or post-acute infection phases. Despite ongoing research, uncertainties persist about precise mechanism virus uses infiltrate system involved entry portals. This review discusses potential routes, including hematogenous anterograde transport. Furthermore, we explore variations neurotropism, neurovirulence, pandemic-associated variants concern. In conclusion, SARS-CoV-2 can infect numerous cells within system, provoke inflammatory responses, induce neuropathological changes.
Language: Английский
Citations
7
Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15
Published: May 17, 2024
Introduction Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available. Methods this study, we conducted a comprehensive clinical and functional healthcare workers (HCWs) former mild COVID-19 (group 1, n = 67), delineate trajectory post-acute imbalance, previously detected in case–control study. Additionally, assessed HCWs for which test before SARS-CoV-2 infection was available 2, 29), who later contracted SARS-CoV-2, aiming validate findings from our prior investigation. We evaluated nervous system heart modulation by means time frequency domain rate variability analysis (HRV) during health surveillance visits. Short-term electrocardiogram (ECG) recordings, were obtained at about 6, 13 months both 6 negative naso-pharyngeal swab (NPS) group 1 1-month NPS 2. used drugs, had comorbidities that HRV, hospitalized severe excluded. Results Group split three subgroups clinically functionally followed at, (subgroup-A, 17), (subgroup-B, 37) (subgroup-C, 13) NPS. subgroup-A, 6-month baseline, spectral components HRV parameters, showed an increase normalized high power (nHF) ( t 2.99, p 0.009), decrease low (nLF) 2.98, 0.009) LF/HF ratio 3.13, 0.006). subgroup B, comparison 13-month nHF 2.54, 0.02); nLF 2.62, 0.01) 4.00, 0.0003). subgroup-C, follow-ups, parameters higher than baseline 2.64, 0.02 2.13, 0.05, respectively); lower respectively), 1.92, 0.08 2.43, 0.03, respectively). A significant proportion reported persistent symptoms seemingly unrelated cardiac balance. 2 HCWs, 2.19, 0.04); 2.15, 0.04) 3.49, 0.002). Conclusion These results consistent epidemiological suggesting risk acute cardiovascular complications first 30 days after COVID-19. The associated phase recovery resolved However, long-term symptoms, dot not seems be related Future research should certainly further whether has role mechanisms long-COVID syndrome.
Language: Английский
Citations
6
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5618 - 5618
Published: March 15, 2023
Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated control of movement and motivation. Alteration DA levels central Parkinson’s disease (PD), common neurodegenerative disorder characterized by motor non-motor manifestations deposition alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized link between PD viral infections. Indeed, different cases parkinsonism been reported following COVID-19. However, whether SARS-CoV-2 may trigger process still matter debate. Interestingly, evidence brain inflammation has described postmortem samples patients infected SARS-CoV-2, which suggests immune-mediated mechanisms triggering neurological sequelae. In this review, we discuss role proinflammatory molecules such as cytokines, chemokines, oxygen reactive species modulating homeostasis. Moreover, review existing literature on possible mechanistic interplay SARS-CoV-2-mediated neuroinflammation nigrostriatal DAergic impairment, cross-talk with aberrant α-syn metabolism.
Language: Английский
Citations
14
Movement Disorders Clinical Practice, Journal Year: 2023, Volume and Issue: 10(S2)
Published: June 1, 2023
Diagnosis and clinical burden in people with Parkinson's disease (PD) is often related to the cardinal motor features (tremor, bradykinesia, rigidity) occurs when at least 40–60% of striatal dopamine nerve terminals are lost.1 However, "Essay on shaking palsy" James Parkinson already reported presence constipation, cognitive dysfunction or sleep disorders addition involvement.2 With introduction l-dopa therapy it became evident that only specific would improve while many others show limited no benefit from medications even if they significantly contribute quality life decline disability. In recent years detection pathological hallmarks tissues beyond central nervous system has supported concept PD a systemic multi-organ condition where less centric various neurotransmitters pathways involved. prodromal phase (the time between onset neurodegeneration occurrence symptoms), orthostatic hypotension (OH), hyposmia, rapid-eye movement (REM) behavior disorder (RBD), pain neuropsychiatric symptoms (ie, subtle frontal lobe deficits depression) may be observed.3 Severe autonomic impairment deterioration advanced stages.4 this Viewpoint, we aimed challenge traditional vision non-motor dichotomy. We have reviewed most relevant respective neurotransmitters' systems involved, suggesting categorization based response replacement therapy. believe these considerations light possibility detect possibly treat before manifestations (Fig. 1). Innervation retina (especially around fovea) mainly dopaminergic, therefore common PD. It expressed as difficulties color contrast during off periods which treatment optimization.5 Diplopia not corrected by dopaminergic develop combination convergence insufficiency exophoria. Shoulder frequently but generally secondary limb rigidity progressively improves once established.5 Bradykinesia usually present satisfying sustained rest-tremor more difficult some patient.6 Medications-related fluctuations, wearing dyskinesias after few patients good l-dopa. Variability brain levels intermittent administration, heterogeneous gastrointestinal function absorption, progressive loss storage capacity development symptoms.7, 8 Therapeutic strategies aiming constant drug delivery receptor stimulation helpful started early, minimize severity complications.7 The pathway plays key role regulation genitourinary system. Dopamine selectively inhibits activates pontine micturition center, explaining frequent urinary Optimizing help management urgency detrusor overactivity PD.5 early bladder also express rapid progression deserves careful assessment treating physicians. non-responsive observed phase. They either misfolded alpha-synuclein accumulation including (structural alterations) consequence dysfunctions affecting other (functional alterations). Olfactory months associated fourfold increase risk within 4–10 years9 overlooked clinicians patients, sometimes confused physiological age-related olfactory decline. lack supports hyposmia does follow parallel decline.10 Abnormalities been structures, whereas involvement peripheral defined. Lewy bodies commonly found regions, supporting hypothesis pathology starting periphery then extending brain.10, 11 Since directly links external environment, could gateway through viruses, novel coronavirus, trigger inflammation ultimately promote neurodegenerative processes.12 Constipation another factor. There increasing interest regarding gut–brain axis, both aggregates reactive enteric gliosis detected fibers duodenal mucosa, PD.13-15 addition, constipation faster involves cholinergic system.16 Finally, alterations gut microbiota composition well documented interventions modulating microbiota.17 Generalized painful sensations dystonic peak-dose dyskinesias, association restless legs syndrome periodic movement. Given mediating several networks (spinal cord, thalamus, basal ganglia, cingulate cortex), suffering an optimized therapy.5 suffer neuropathic independently complications glutamate, norepinephrine serotonin. A broader approach considers multiple drugs opiate warranted given its relevance life.18 Mild executive functions, working memory, attention, planning problem solving features. Dementia long survival underpinned dysfunction, diffuse body amyloid elderly patients.19 Rivastigmine, acetylcholinesterase inhibitor, function, attention behavioral dementia for drugs. Presence different regional patterns explain unresponsive decline.20 Gait postural instability amongst disabling overlap resulting autonomy worsening life. unsatisfying device aided therapies suggests non-dopaminergic nuclei.21 Abnormal plasticity pharmacodynamic changes transmission neurobiological substrates dyskinesia. determines internalization A2A-D2 heteromers compensatory upregulation A2A homomers, leading impaired firing pattern striato-pallidal pathway.22 Hence, dyskinesia challenging requires diversified targeting especially glutamatergic modulation amantadine, NMDA antagonist) implementation therapies. Strategies serotonin successful although animal models suggest neurotransmitter Psychosis characterized hallucinations, delusions (false beliefs against contrary knowledge) delirium. occur context triggered therapy.23 Modulation along use atypical antipsychotic pimavanserin (currently available USA) should represent choice, older led manifestations. Impulsivity ICD DA agonists.24-26 This notion can managed OH estimated prevalence ranging 30–65% patients. occasionally feature across all stages disease. main played noradrenaline explains why disruption noradrenergic underlines cardiovascular abnormalities OH. Extracardiac, importantly, cardiac sympathetic denervation additional parasympathetic compartment baroreflex.27 To date, standardized lacking relationship still debated,28 together inclusion among potential side effects levodopa agonists, non-pharmacological treatments recommended first choice. These result complex interplay systems, partially treatment. Indeed, category comprises presenting motor, components, likely reflecting anatomical neurochemical circuits. RBD strong factor predictor synucleinopathies (25–40% 5 years, 40–65% 10 years).13, 29 Several neuroimaging functional studies support nigrostriatal degeneration genesis since alone.30 depletion locus coeruleus studies.31 hypothesis, study suggested efficacy safinamide, medication nondopaminergic actions (inhibition monoamine oxidase-B, glutamate release) improving RBD.32 Depression depression-related listed criteria Prodromal PD.33 comorbid anxiety separate entity relation fluctuations periods. dopamine, extra-striatal serotonergic afferent midbrain play important depression.34 patterns, occurring adverse effects, need considered approaching randomized trials antidepressant one placebo controlled documenting effect pramipexole.35 depressive require and/or apathetic present.5 Apathy alone depression anxiety. prominent dysregulation causative factors determining apathy introducing persistence monitoring neuropsychological skills.36 An work view organs involved poorly addressed life, decline.5, 37 Moreover, resistant constitute major target palliative late stage disease.38 focus impact global disease, expectancy cost care.5 Indeed multidomain physical opposed individuals who manifest predominant mild mood course benign. Similar worse prognosis, higher impairment, death.39 Overall findings redefinition process involving rates progression. pattern, mirror classic well-documented Identification tracking those evaluation properly define prognosis.37, 39 neuropathological might alpha synuclein misfolding aggregation neurons.11 overlapping processes (amyloid Tau) concomitant cerebrovascular increasingly documents heterogeneity patient therapeutic approaches. Current "clinical markers" heavily weighted towards objective pharmacological research expand particularly compounds serotoninergic, purinergic pathways. Our suggestion new diagnosis rapidly adopted, encompassing addressing their contribution detection, Recent discoveries biomarkers indicate change our dopamine-centric perspective want test implement modifying become manifest.40 Figure 1 was created BioRender.com. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: Design, Execution, Review Critique; (3) Manuscript Preparation: Writing draft, Critique. A.A.: C; 2 3 M.C.: A, A.E.: Ethical Compliance Statement: Informed consent necessary work, approval institutional review board required. confirm read Journal's position issues ethical publication affirm consistent guidelines. Funding Sources Conflicts Interest: No funding received there conflicts declare. Financial Disclosure Previous 12 Months: A.A. compensation consultancy speaker-related activities UCB, Britannia, AbbVie, Zambon, Bial, Ever Pharma, Theravance Biopharma, Roche, General Electric, Medscape. He receives Chiesi Pharmaceuticals, Lundbeck, Movement Disorders Society, Horizon2020 Grant 825785, 101016902, Ministry Education University (MIUR) ARS01_01081, Cariparo Foundation. M.C. travel grants Lusofarmaco Zambon. A.E. nothing
Language: Английский
Citations
13
Diagnostics, Journal Year: 2023, Volume and Issue: 13(12), P. 1990 - 1990
Published: June 7, 2023
Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by COVID, with potential clinical issues different fields, including problems school performance and daily activities. Yet, the pathophysiologic bases are largely unknown, it is difficult to predict who will develop syndrome. this multidisciplinary review, we summarise latest scientific data regarding its impact on children. Special attention given diagnostic tests, order help physicians find disease markers quantify impairment. Specifically, assess respiratory, upper airways, cardiac, neurologic motor psychological aspects. Finally, also propose approach.
Language: Английский
Citations
13