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Cells Nov 2023A growing body of evidence indicates that a neuropathological cross-talk takes place between the coronavirus disease 2019 (COVID-19) -the pandemic severe pneumonia that... (Review)
Review
A growing body of evidence indicates that a neuropathological cross-talk takes place between the coronavirus disease 2019 (COVID-19) -the pandemic severe pneumonia that has had a tremendous impact on the global economy and health since three years after its outbreak in December 2019- and Alzheimer's Disease (AD), the leading cause of dementia among human beings, reaching 139 million by the year 2050. Even though COVID-19 is a primary respiratory disease, its causative agent, the so-called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is also endowed with high neuro-invasive potential (Neurocovid). The neurological complications of COVID-19, resulting from the direct viral entry into the Central Nervous System (CNS) and/or indirect systemic inflammation and dysregulated activation of immune response, encompass memory decline and anosmia which are typically associated with AD symptomatology. In addition, patients diagnosed with AD are more vulnerable to SARS-CoV-2 infection and are inclined to more severe clinical outcomes. In the present review, we better elucidate the intimate connection between COVID-19 and AD by summarizing the involved risk factors/targets and the underlying biological mechanisms shared by these two disorders with a particular focus on the Angiotensin-Converting Enzyme 2 (ACE2) receptor, APOlipoprotein E (APOE), aging, neuroinflammation and cellular pathways associated with the Amyloid Precursor Protein (APP)/Amyloid beta (Aβ) and tau neuropathologies. Finally, the involvement of ophthalmological manifestations, including vitreo-retinal abnormalities and visual deficits, in both COVID-19 and AD are also discussed. Understanding the common physiopathological aspects linking COVID-19 and AD will pave the way to novel management and diagnostic/therapeutic approaches to cope with them in the post-pandemic future.
Topics: Humans; COVID-19; SARS-CoV-2; Alzheimer Disease; Pandemics; Amyloid beta-Peptides; Nervous System Diseases
PubMed: 37998336
DOI: 10.3390/cells12222601 -
Brain, Behavior, & Immunity - Health Jul 2023One of the predominant symptoms of the COVID-19 virus is the complete (anosmia) or partial (hyposmia) loss of smell. Anosmia may be a critical neurocognitive symptom...
One of the predominant symptoms of the COVID-19 virus is the complete (anosmia) or partial (hyposmia) loss of smell. Anosmia may be a critical neurocognitive symptom because there is an empirically demonstrated association of anosmia with neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, etc. The present study assessed the neurocognitive disorder patterns in recovered COVID-19 patients who either self-reported anosmia or its absence. Of the 60 adult participants (n = 32 males, n = 28 females; = 20.78 years, range = 18-31 years), 15 reported COVID-19 induced anosmia, 15 reported COVID-19 without anosmia, and 30 reported not having contracted COVID-19. The participants were first administered a 10-item smell test, and analysis of variance revealed significantly better scores for the control group than the other two groups. Further, there was no significant difference in smell scores between the patients who self-reported anosmia or denied it. This statistical pattern was consistent across all neuropsychological tests: short- and long-term verbal memory, digit span, Trail Making, and a self-report 46-item neurocognitive scale. Regardless of the self-report of anosmia or denial, all thirty COVID-19 patients scored significantly poorer than the control group on all of the tests and neurocognitive scale. In summary, the self-report of anosmia appears to be unreliable, and the COVID-19 patients who were found to be anosmic on the initial objective smell test demonstrated poorer neuropsychological performance than controls.
PubMed: 37215309
DOI: 10.1016/j.bbih.2023.100632 -
Asian Journal of Surgery Nov 2023
Topics: Humans; Ageusia; Propofol; Anosmia; Anesthesia, General
PubMed: 37734983
DOI: 10.1016/j.asjsur.2023.07.001 -
Ear, Nose, & Throat Journal Jun 2024To systematically review the cases of anosmia or ageusia after receiving the coronavirus disease 2019 (COVID-19) vaccine. A systematic search was conducted in... (Review)
Review
To systematically review the cases of anosmia or ageusia after receiving the coronavirus disease 2019 (COVID-19) vaccine. A systematic search was conducted in electronic databases, including Web of Science, Scopus, Embase, and PubMed, to identify any published study that evaluated the anosmia or ageusia after receiving the COVID-19 vaccine, including case reports, case series, letter to editor articles with reported cases regarding our topic, or observational studies with at least 1 eligible patient consisted with our criteria. We excluded the studies that reported anosmia or ageusia due to COVID-19 infection and non-COVID-19 vaccines. Five studies consisting of 11 patients were included in this systematic review. Of the 11 patients, 5 patients had received the Pfizer COVID-19 vaccine and 6 patients received the Oxford-AstraZeneca COVID-19 vaccine, of which 6 patients developed symptoms after the first dose of vaccination and 5 patients were symptomatic after the second vaccine dose. Most of the patients developed symptoms within 1 week after the vaccination. The disorders of the patients included partial or total anosmia, parosmia, phantosmia, hyposmia, ageusia, and dysgeusia. Also, the patients had symptoms other than smell or taste disorders, including arthralgia, fever, chills, rhinorrhea, myalgia, abdominal pain, fatigue, muscle weakness, altered bowel pattern, aural fullness, tinnitus, and headache. Most of the evaluated patients did not receive any treatment as for their disorders. However, in some cases, treatment with oral corticosteroids or dietary supplementation was required. Anosmia and ageusia are important symptoms of COVID-19 vaccination. These symptoms will resolve without any treatment in most cases, although some interventions may be needed in some patients.
Topics: Humans; Ageusia; Anosmia; COVID-19; COVID-19 Vaccines; Female; Male; Vaccination; SARS-CoV-2; Middle Aged; Adult; BNT162 Vaccine; Aged
PubMed: 38411125
DOI: 10.1177/01455613241233098 -
Medicina (Kaunas, Lithuania) Aug 2023: Hypo/anosmia is a characteristic symptom of COVID-19 infection. The aim of this study is to investigate the time of smell recovery and to identify a possible order of... (Observational Study)
Observational Study
: Hypo/anosmia is a characteristic symptom of COVID-19 infection. The aim of this study is to investigate the time of smell recovery and to identify a possible order of perception recovery of different odors in COVID-19 patients. : A prospective observational study was conducted on not hospitalized COVID-19 patients, selected according to eligible criteria. The study was approved by the Ethical Committee. A questionnaire formulated by our team was submitted to patients in order to know the duration of the hypo/anosmia and hypo/ageusia and the order of odor recovery: vanillin (mixed olfactory/gustatory substances), phenyl ethyl alcohol (rosewater) (pure olfactory substances), eucalyptol (mixed olfactory/trigeminal substances), and eugenol (mixed olfactory/trigeminal/gustatory substances). : 181 patients were included. Hypo/ageusia and hypo/anosmia lasted on average 10.25 (±8.26) and 12.8 (±8.80) days, respectively. The most frequent odor recovery sequence was: (1) phenyl ethyl alcohol; (2) eucalyptol; (3) vanillin; and (4) eugenol. In COVID-19 patients, hypo/anosmia occurs more often in women and at a young age. : This preliminary investigation highlighted novel data: there is a chronological order in perception recovery of different olfactory substances and, therefore, in the restoration of the various sensitive nerve pathways involved in the sense of smell.
Topics: Humans; Female; Smell; Anosmia; Ageusia; Eucalyptol; Eugenol; COVID-19; Phenylethyl Alcohol
PubMed: 37763630
DOI: 10.3390/medicina59091511 -
Parkinsonism & Related Disorders May 2024Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying...
INTRODUCTION
Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD.
METHODS
Longitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis.
RESULTS
Compared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus.
CONCLUSIONS
The atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.
Topics: Humans; Parkinson Disease; Male; Female; Aged; Middle Aged; Longitudinal Studies; Magnetic Resonance Imaging; REM Sleep Behavior Disorder; Olfaction Disorders; Atrophy; Anosmia; Disease Progression; Brain
PubMed: 38430690
DOI: 10.1016/j.parkreldis.2024.106072 -
Acta Neuropathologica Mar 2024Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis,...
Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research-L-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan aptamer precipitation assay, and liquid chromatography-mass spectrometry proteomics. We discovered that hundreds of proteins were upregulated in the CSF, blood, or urine of PD patients, prodromal PD patients with DAT deficit and REM sleep behavior disorder or anosmia, and non-manifesting genetic carriers of LRRK2 and GBA mutations. We nominate multiple novel hits across our analyses as promising markers of early PD, including DOPA decarboxylase (DDC), also known as L-aromatic acid decarboxylase (AADC), sulfatase-modifying factor 1 (SUMF1), dipeptidyl peptidase 2/7 (DPP7), glutamyl aminopeptidase (ENPEP), WAP four-disulfide core domain 2 (WFDC2), and others. DDC, which catalyzes the final step in dopamine synthesis, particularly stands out as a novel hit with a compelling mechanistic link to PD pathogenesis. DDC is consistently upregulated in the CSF and urine of treatment-naïve PD, prodromal PD, and GBA or LRRK2 carrier participants by all three proteomics methods. We show that CSF DDC levels correlate with clinical symptom severity in treatment-naïve PD patients and can be used to accurately diagnose PD and prodromal PD. This suggests that urine and CSF DDC could be a promising diagnostic and prognostic marker with utility in both clinical care and translational research.
Topics: Humans; Parkinson Disease; Dopa Decarboxylase; Proteomics; Biomarkers; Plasma; Oxidoreductases Acting on Sulfur Group Donors; Aromatic-L-Amino-Acid Decarboxylases
PubMed: 38467937
DOI: 10.1007/s00401-024-02706-0 -
International Journal of Molecular... Aug 2023One of the most prevalent causes of olfactory loss includes traumatic brain injury with subsequent shearing of olfactory axons at the level of the cribriform plate...
One of the most prevalent causes of olfactory loss includes traumatic brain injury with subsequent shearing of olfactory axons at the level of the cribriform plate (anterior skull base). Scar tissue at this level may prevent axonal regrowth toward the olfactory bulb. Currently, there is no cure for this debilitating and often permanent condition. One promising therapeutic concept is to implant a synthetic scaffold with growth factors through the cribriform plate/scar tissue to induce neuroregeneration. The first step toward this goal is to investigate the optimum conditions (growth factors, extracellular matrix proteins) to boost this regeneration. However, the lack of a specifically tailored in vitro model and an automated procedure for quantifying axonal length limits our ability to address this issue. The aim of this study is to create an automated quantification tool to measure axonal length and to determine the ideal growth factors and extracellular proteins to enhance axonal regrowth of olfactory sensory neurons in a mouse organotypic 2D model. We harvested olfactory epithelium (OE) of C57BL/6 mice and cultured them during 15 days on coverslips coated with various extracellular matrix proteins (Fibronectin, Collagen IV, Laminin, none) and different growth factors: fibroblast growth factor 2 (FGF2), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), retinoic acid (RA), transforming growth factor β (TGFβ), and none. We measured the attachment rate on coverslips, the presence of cellular and axonal outgrowth, and finally, the total axonal length with a newly developed automated high-throughput quantification tool. Whereas the coatings did not influence attachment and neuronal outgrowth rates, the total axonal length was enhanced on fibronectin and collagen IV ( = 0.001). The optimum growth factor supplementation media to culture OE compared to the control condition were as follows: FGF2 alone and FGF2 from day 0 to 7 followed by FGF2 in combination with NGF from day 7 to 15 ( < 0.0001). The automated quantification tool to measure axonal length outperformed the standard Neuron J application by reducing the average analysis time from 22 to 3 min per specimen. In conclusion, robust regeneration of murine olfactory neurons in vitro can be induced, controlled, and efficiently measured using an automated quantification tool. These results will help advance the therapeutic concept closer toward preclinical studies.
Topics: Animals; Mice; Mice, Inbred C57BL; Olfactory Receptor Neurons; Fibronectins; Cicatrix; Fibroblast Growth Factor 2; Nerve Growth Factor; Axons; Extracellular Matrix Proteins; Collagen Type IV; Culture Media
PubMed: 37629041
DOI: 10.3390/ijms241612863 -
Journal of Trace Elements in Medicine... Dec 2023Acute inflammatory or neuropsychiatric symptoms, such as headache, fatigue, anosmia, and hyposmia, sometimes persist for more than 30 days or longer than 12 weeks after...
OBJECTIVES
Acute inflammatory or neuropsychiatric symptoms, such as headache, fatigue, anosmia, and hyposmia, sometimes persist for more than 30 days or longer than 12 weeks after infection with the Omicron variant of SARS‑CoV‑2 (hereafter referred to as COVID-19). The aim of this study was to determine whether detection of zinc concentration or vitamin D concentration could provide treatment benefits for patients with COVID-19, thus reducing the risk of them experiencing long COVID.
METHODS
The interval between the date of COVID-19 diagnosis and the date of visit to pulmonary department for prolonged symptoms of COVID-19 was recorded for statistical analysis. Inductively coupled plasma mass spectrometry for detecting zinc and chemiluminescence immunoassay for detecting vitamin D were performed in laboratory tests.
RESULTS
Fifty-five patients were included. Of the participants, 29.1 % and 27.3 % had vitamin D and zinc deficiency, respectively. On average, the patients underwent long COVID treatment for 31.7 ± 17.7 days. A positive statistical correlation was observed between vitamin D and zinc concentrations (Pearson's correlation = 0.378). Compared with sufficient zinc levels, zinc deficiency was associated with a higher fibrinogen level (p < 0.05). Within 30 days, the observed vitamin D deficiency rate was only 21.4 %; after 30 days, the vitamin D deficiency rate rose to 37.0 % (McNemar's chi-square test; p < 0.05).
CONCLUSION
Zinc deficiency correlates to acute and persistent inflammation and vitamin D deficiency is associated with delayed recovery in long COVID syndrome.
Topics: Humans; Vitamin D; Post-Acute COVID-19 Syndrome; COVID-19 Testing; SARS-CoV-2; COVID-19; Vitamins; Vitamin D Deficiency; Minerals; Zinc
PubMed: 37566973
DOI: 10.1016/j.jtemb.2023.127278 -
Frontiers in Immunology 2023While the short-term symptoms of post-COVID syndromes (PCS) are well-known, the long-term clinical characteristics, risk factors and outcomes of PCS remain unclear.... (Observational Study)
Observational Study
BACKGROUND
While the short-term symptoms of post-COVID syndromes (PCS) are well-known, the long-term clinical characteristics, risk factors and outcomes of PCS remain unclear. Moreover, there is ongoing discussion about the effectiveness of post-infection vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) to aid in PCS recovery.
METHODS
In this longitudinal and observational case-control study we aimed at identifying long-term PCS courses and evaluating the effects of post-infection vaccinations on PCS recovery. Individuals with initial mild COVID-19 were followed for a period of 15 months after primary infection. We assessed PCS outcomes, distinct symptom clusters (SC), and SARS-CoV-2 immunoglobulin G (IgG) levels in patients who received SARS-CoV-2 vaccination, as well as those who did not. To identify potential associating factors with PCS, we used binomial regression models and reported the results as odds ratios (OR) with 95% confidence intervals (95%CI).
RESULTS
Out of 958 patients, follow-up data at 15 month after infection was obtained for 222 (23.2%) outpatients. Of those individuals, 36.5% (81/222) and 31.1% (69/222) were identified to have PCS at month 10 and 15, respectively. Fatigue and dyspnea (SC2) rather than anosmia and ageusia (SC1) constituted PCS at month 15. SARS-CoV-2 IgG levels were equally distributed over time among age groups, sex, and absence/presence of PCS. Of the 222 patients, 77.0% (171/222) were vaccinated between 10- and 15-months post-infection, but vaccination did not affect PCS recovery at month 15. 26.3% of unvaccinated and 25.8% of vaccinated outpatients improved from PCS (p= .9646). Baseline headache (SC4) and diarrhoea (SC5) were risk factors for PCS at months 10 and 15 (SC4: OR 1.85 (95%CI 1.04-3.26), p=.0390; SC5: OR 3.27(95%CI 1.54-6.64), p=.0009).
CONCLUSION
Based on the specific symptoms of PCS our findings show a shift in the pattern of recovery. We found no effect of SARS-CoV-2 vaccination on PCS recovery and recommend further studies to identify predicting biomarkers and targeted PCS therapeutics.
Topics: Humans; Case-Control Studies; COVID-19; COVID-19 Vaccines; Immunoglobulin G; Outpatients; Post-Acute COVID-19 Syndrome; Risk Factors; SARS-CoV-2; Vaccination; Longitudinal Studies
PubMed: 37781408
DOI: 10.3389/fimmu.2023.1226622