Brain Metabolic Correlates of Persistent Olfactory Dysfunction after SARS-Cov2 Infection.
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ABSTRACT:
SUBMITTER: Donegani MI
PROVIDER: S-EPMC7998481 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThis research aims to study structural brain changes in patients with persistent olfactory dysfunctions after coronavirus disease 2019 (COVID-19).MethodsCOVID-19 patients were evaluated using T1-weighted and diffusion tensor imaging (DTI) on a 3T MRI scanner, 9.94 ± 3.83 months after COVID-19 diagnosis. Gray matter (GM) voxel-based morphometry was performed using FSL-VBM. Voxelwise statistical analysis of the fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was carried out with the tract-based spatial statistics in the olfactory system. The smell identification test (UPSIT) was used to classify patients as normal olfaction or olfactory dysfunction groups. Intergroup comparisons between GM and DTI measures were computed, as well as correlations with the UPSIT scores.ResultsForty-eight COVID-19 patients were included in the study. Twenty-three were classified as olfactory dysfunction, and 25 as normal olfaction. The olfactory dysfunction group had lower GM volume in a cluster involving the left amygdala, insular cortex, parahippocampal gyrus, frontal superior and inferior orbital gyri, gyrus rectus, olfactory cortex, caudate, and putamen. This group also showed higher MD values in the genu of the corpus callosum, the orbitofrontal area, the anterior thalamic radiation, and the forceps minor; and higher RD values in the anterior corona radiata, the genu of the corpus callosum, and uncinate fasciculus compared with the normal olfaction group. The UPSIT scores for the whole sample were negatively associated with both MD and RD values (p-value ≤0.05 FWE-corrected).InterpretationThere is decreased GM volume and increased MD in olfactory-related regions explaining prolonged olfactory deficits in post-acute COVID-19 patients.
| S-EPMC9878006 | biostudies-literature
Project description:There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials.
| S-SCDT-EMM-2020-13426 | biostudies-other
Project description:SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.
| S-EPMC9330630 | biostudies-literature
Project description:Background: One of the main symptoms of COVID-19 is hyposmia or even anosmia. Olfactory identification is most often affected. In addition, some cognitive disorders tend to appear following the infection, particularly regarding executive functions, attention, and memory. Olfaction, and especially olfactory identification, is related to semantic memory which manages general knowledge about the world. The main objective of this study was to determine whether semantic memory is impaired in case of persistent post COVID-19 olfactory disorders. Methods: 84 patients (average age of 42.8 ± 13.6 years) with post COVID-19 olfactory loss were included after consulting to the ENT department. The clinical evaluation was carried out with the Pyramid and Palm Tree Test, the word-retrieval task from the Grémots, the Sniffin' Sticks Test and the Computerised Olfactory Test for the Diagnosis of Alzheimer's Disease. Results: Semantic memory was impaired in 20% (n = 17) of patients, especially in the 19-39 age-group. The olfactory threshold was only significantly correlated with the semantic memory scores. Conclusions: Similar to all cognitive disorders, semantic disorders can have a negative impact on quality of life if left untreated. It is essential to carry out specific assessments of post COVID-19 patients to accurately determine their disorders and to put in place the best possible rehabilitation, such as speech and language therapy, to avoid quality-of-life impairment.
| S-EPMC9221020 | biostudies-literature
Project description:SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in human, and olfactory dysfunction represents as one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism how SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowman's gland cells in the OE were identified as the major target cells of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration, and directly impairs the uniformity of OE structure. Combined transcriptomic and quantitative proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19.
2021-06-22 | PXD026854 |
Project description:HEK293T stable express hACE2 was infected by SARS-CoV-2 (WA1) and RNA-seq was performed to profile host gene expression in response to SARS-COV-2 infection
2021-04-16 | GSE169158 | GEO
Project description:Like other infectious diseases, COVID-19 shows a clinical outcome enormously variable, ranging from asymptomatic to lethal. In Italy, like in other countries, old male individuals, with one or more comorbidity, are the most susceptible group, and show, consequently, the highest mortality, and morbidity, including lethal respiratory distress syndrome, as the most common complication. In addition, another extraordinary peculiarity, that is a surprising resistance to COVID-19, characterizes some Italian nonagenarians/centenarians. Despite having the typical COVID-19 signs and/or symptoms, such exceptional individuals show a surprising tendency to recover from illness and complications. On the other hand, long-lived people have an optimal performance of immune system related to an overexpression of anti-inflammatory variants in immune/inflammatory genes, as demonstrated by our and other groups. Consequently, we suggest long-lived people as an optimal model for detecting genetic profiles associated with the susceptibility and/or protection to COVID-19, to utilize as potential pharmacological targets for preventing or reducing viral infection in more vulnerable individuals.
| S-EPMC7885677 | biostudies-literature
Project description: Not available
| S-EPMC9707023 | biostudies-literature
Project description:Persistent olfactory dysfunction (OD) is the second most common symptom of post coronavirus disease-19 (COVID-19) now being termed long-COVID. Its prevalence after recovery from COVID-19 is estimated to be 12% after nearly 6 months of follow-up. It thus becomes imperative for the treating clinicians to update themselves with the pathophysiology of this post COVID disability as well as the tools for diagnosis and the available treatment options. A systematic literature search was performed as per PRISMA guidelines in MEDLINE, Cochrane Library, LILACS, Google Scholar, ClinicalTrials.gov, and medRxiv databases. The keywords used were covid-19, Olfactory Disorders, Smell, Anosmia, PVOD, Post Viral Olfactory Disorders, post-covid and post haul. All articles were studied for definition, mechanism, diagnostic tests and treatment options for post COVID OD. 33 published articles and 8 ongoing trials were found relevant and included after full-text review. SARS-CoV-2 can cause conductive, neural and central OD. Olfactory evaluation can be done both subjectively (visual analogue scale) and objectively (Sniffin' sticks, Sinonasal Outcome Test, University of Pennsylvania Smell Identification Test and modified Davidson's alcohol sniff test). They can be used to detect and follow-up patients. Despite several on-going clinical trials, the most reliable and advisable treatment option available till date is olfactory training.
| S-EPMC8260324 | biostudies-literature
Project description:BackgroundOlfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little guidance on how best to treat this condition. A variety of interventions have been suggested to promote recovery, including medication and olfactory training. However, it is uncertain whether any intervention is of benefit. This is an update of the 2021 review with one additional study added. OBJECTIVES: 1) To evaluate the benefits and harms of any intervention versus no treatment for people with persisting olfactory dysfunction due to COVID-19 infection. 2) To keep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance that had persisted for at least four weeks. We included any intervention compared to no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome.Main resultsWe included two studies with 30 participants. The studies evaluated the following interventions: systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant and palmitoylethanolamide plus luteolin. Systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant compared to no intervention We included a single RCT with 18 participants who had anosmia for at least 30 days following COVID-19 infection. Participants received a 15-day course of oral corticosteroids combined with nasal irrigation (consisting of an intranasal corticosteroid/mucolytic/decongestant solution) or no intervention. Psychophysical testing was used to assess olfactory function at 40 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results. Palmitoylethanolamide plus luteolin compared to no intervention We included a single RCT with 12 participants who had anosmia or hyposmia for at least 90 days following COVID-19 infection. Participants received a 30-day course of palmitoylethanolamide and luteolin or no intervention. Psychophysical testing was used to assess olfactory function at 30 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results.Authors' conclusionsThere is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.
| S-EPMC9443431 | biostudies-literature