Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

COVID-19 and the risk of neuromyelitis optica spectrum disorder: a Mendelian randomization study

ABSTRACT:

Background

An increasing number of studies have elucidated a close nexus between COVID-19 phenotypes and neuromyelitis optica spectrum disorder (NMOSD), yet the causality between them remains enigmatic.

Methods

In this study, we conducted a Mendelian randomization (MR) analysis employing summary data sourced from genome-wide association studies (GWAS) pertaining to COVID-19 susceptibility, hospitalization, severity, and NMOSD. The primary MR analysis employed the Inverse variance weighted (IVW) approach, which was supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. We implemented various sensitivity analyses including Cochran’s Q test, MR-PRESSO method, MR-Egger intercept, leave-one-out analysis, and funnel plot.

Results

The MR results demonstrated a nominal association between COVID-19 susceptibility and the risk of AQP4+ NMOSD, as evidenced by the IVW method (OR = 4.958; 95% CI: 1.322-18.585; P = 0.018). Conversely, no causal association was observed between COVID-19 susceptibility, hospitalization, or severity and the increased risk of NMOSD, AQP4-NMOSD, or AQP4+ NMOSD. The comprehensive sensitivity analyses further bolstered the robustness and consistency of the MR estimates.

Conclusion

Our findings provide compelling evidence for a causal effect of COVID-19 phenotype on AQP4+ NMOSD, shedding new light on the understanding of the comorbidity between COVID-19 and NMOSD.

SUBMITTER:

PROVIDER: S-EPMC10414539 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

The levels of circulating cytokines and risk of neuromyelitis optica spectrum disorder: a Mendelian randomization study.

Project description:BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease affecting the central nervous system (CNS). NMOSD pathogenesis involves systemic inflammation. However, a causal relationship between circulating cytokine levels and NMOSD remains unclear.MethodsMendelian randomization (MR) approaches were used to investigate the potential association between genetically determined circulating 19 inflammatory cytokines and 12 chemokines levels and the risk of developing NMOSD.ResultsAfter Bonferroni correction, the risk of aquaporin 4-antibody (AQP4-ab)-positive NMOSD was suggested to be causally associated with the circulating levels of three cytokines, including interleukin (IL)-4 [odds ratio (OR): 11.01, 95% confidence interval (CI): 1.16-104.56, P = 0.037], IL-24 (OR: 161.37; 95% CI: 2.46-10569.21, P = 0.017), and C-C motif chemokine 19 (CCL19) (OR: 6.87, 95% CI: 1.78-26.93, P = 0.006).ConclusionThese findings suggest that a genetic predisposition to higher levels of IL-4, IL-24, and CCL19 may exert a causal effect on the risk of AQP4-ab-positive NMOSD. Further studies are warranted to clarify how these cytokines affect the development of AQP4-ab-positive NMOSD.

| S-EPMC11246864 | biostudies-literature

Causal relationships of grey matter structures in multiple sclerosis and neuromyelitis optica spectrum disorder: insights from Mendelian randomization.

Project description:Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple sclerosis and neuromyelitis optica spectrum disorder in observational studies, it is unclear whether these associations indicate causal relationships between these diseases and grey matter changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationships between 202 grey matter imaging-derived phenotypes (33 224 individuals) and multiple sclerosis (47 429 cases and 68 374 controls) as well as neuromyelitis optica spectrum disorder (215 cases and 1244 controls). Our results suggested that genetically predicted multiple sclerosis was positively associated with the surface area of the left parahippocampal gyrus (β = 0.018, P = 2.383 × 10-4) and negatively associated with the volumes of the bilateral caudate (left: β = -0.020, P = 7.203 × 10-5; right: β = -0.021, P = 3.274 × 10-5) and putamen nuclei (left: β = -0.030, P = 2.175 × 10-8; right: β = -0.024, P = 1.047 × 10-5). In addition, increased neuromyelitis optica spectrum disorder risk was associated with an increased surface area of the left paracentral gyrus (β = 0.023, P = 1.025 × 10-4). Conversely, no evidence was found for the causal impact of grey matter imaging-derived phenotypes on disease risk in the opposite direction. We provide suggestive evidence that genetically predicted multiple sclerosis and neuromyelitis optica spectrum disorder are associated with increased cortical surface area and decreased subcortical volume in specific regions. Our findings shed light on the associations of grey matter alterations with the risk of multiple sclerosis and neuromyelitis optica spectrum disorder.

| S-EPMC11420985 | biostudies-literature

Causal relationships between susceptibility and severity of COVID-19 and neuromyelitis optica spectrum disorder (NMOSD) in European population: a bidirectional Mendelian randomized study.

Project description:BackgroundNeurological disorders can be caused by viral infections. The association between viral infections and neuromyelitis optica spectrum disorder (NMOSD) has been well-documented for a long time, and this connection has recently come to attention with the occurrence of SARS-CoV-2 infection. However, the precise nature of the causal connection between NMOSD and COVID-19 infection remains uncertain.MethodsTo investigate the causal relationship between COVID-19 and NMOSD, we utilized a two-sample Mendelian randomization (MR) approach. This analysis was based on the most extensive and recent genome-wide association study (GWAS) that included SARS-CoV-2 infection data (122616 cases and 2475240 controls), hospitalized COVID-19 data (32519 cases and 2062805 controls), and data on severe respiratory confirmed COVID-19 cases (13769 cases and 1072442 controls). Additionally, we incorporated a GWAS meta-analysis comprising 132 cases of AQP4-IgG-seropositive NMOSD (NMO-IgG+), 83 cases of AQP4-IgG-seronegative NMOSD (NMO-IgG-), and 1244 controls.ResultsThe findings of our study indicate that the risk of developing NMO-IgG+ is elevated when there is a genetic predisposition to SARS-CoV-2 infection (OR = 5.512, 95% CI = 1.403-21.657, P = 0.014). Furthermore, patients with genetically predicted NMOSD did not exhibit any heightened susceptibility to SARS-CoV2 infection, COVID-19 hospitalization, or severity.Conclusionour study using Mendelian randomization (MR) revealed, for the first time, that the presence of genetically predicted SARS-CoV2 infection was identified as a contributing factor for NMO-IgG+ relapses.

| S-EPMC10726038 | biostudies-literature

High risk of postpartum relapses in neuromyelitis optica spectrum disorder.

Project description:OBJECTIVE:To study the effect of pregnancy on the frequency of neuromyelitis optica spectrum disorder (NMOSD) relapse and evaluate rates of pregnancy-related complications in an international multicenter setting. METHODS:We administered a standardized survey to 217 women with NMOSD from 7 medical centers and reviewed their medical records. We compared the annualized relapse rate (ARR) during a baseline period 2 years prior to a participant's first pregnancy to that during pregnancy and to the 9 months postpartum. We also assessed pregnancy-related complications. RESULTS:There were 46 informative pregnancies following symptom onset in 31 women with NMOSD. Compared to baseline (0.17), ARR was increased both during pregnancy (0.44; p = 0.035) and during the postpartum period (0.69; p = 0.009). The highest ARR occurred during the first 3 months postpartum (ARR 1.33). A total of 8 of 76 (10.5%) with onset of NMOSD prior to age 40 experienced their initial symptom during the 3 months postpartum, 2.9 times higher than expected. CONCLUSIONS:The postpartum period is a particularly high-risk time for initial presentation of NMOSD. In contrast to published observations in multiple sclerosis, in neuromyelitis optica, relapse rate during pregnancy was also increased, although to a lesser extent than after delivery.

| S-EPMC5705247 | biostudies-literature

Oily fish and raw vegetable consumption can decrease the risk of AQP4-positive neuromyelitis optica spectrum disorders: a Mendelian-randomization study.

Project description:Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory disorders of the central nervous system targeting aquaporin-4 (AQP4). The risk factors for NMOSD remain to be determined, though they may be related to diet and nutrition. This study aimed to explore the possibility of a causal relationship between specific food intake and AQP4-positive NMOSD risk. The study followed a two-sample Mendelian randomization (MR) design. Genetic instruments and self-reported information on the intake of 29 types of food were obtained from a genome-wide association study (GWAS) on 445,779 UK Biobank participants. A total of 132 individuals with AQP4-positive NMOSD and 784 controls from this GWAS were included in our study. The associations were evaluated using inverse-variance-weighted meta-analysis, weighted-median analysis, and MR-Egger regression. A high consumption of oily fish and raw vegetables was associated with a decreased risk of AQP4-positive NMOSD (odds ratio [OR] = 1.78 × 10-16, 95% confidence interval [CI] = 2.60 × 10-25-1.22 × 10-7, p = 0.001; OR = 5.28 × 10-6, 95% CI = 4.67 × 10-11-0.598, p = 0.041, respectively). The results were consistent in the sensitivity analyses, and no evidence of directional pleiotropy was observed. Our study provides useful implications for the development of AQP4-positive NMOSD prevention strategies. Further research is needed to determine the exact causal relationship and mechanisms underlying the association between specific food intake and AQP4-positive NMOSD.

| S-EPMC10256733 | biostudies-literature

Sleep abnormality in neuromyelitis optica spectrum disorder.

Project description:ObjectivesWe investigated the sleep structure of patients with neuromyelitis optica spectrum disorder (NMOSD) and the association of abnormalities with brain lesions.MethodsThis was a prospective cross-sectional study. Thirty-three patients with NMOSD and 20 matched healthy individuals were enrolled. Demographic and clinical characteristics of patients were collected. Questionnaires were used to assess quality of sleep, daytime sleepiness, fatigue, and depression. Nocturnal polysomnography was performed.ResultsCompared with healthy controls, patients with NMOSD had decreases in sleep efficiency (7%; p = 0.0341), non-REM sleep N3 (12%; p < 0.0001), and arousal index (6; p = 0.0138). REM sleep increased by 4% (p = 0.0423). There were correlations between arousal index and REM% or Epworth Sleepiness Scale (r = -0.0145; p = 0.0386, respectively). Six patients with NMOSD (18%, 5 without infratentorial lesions and 1 with infratentorial lesions) had a hypopnea index >5, and all of those with sleep apnea had predominantly the peripheral type. The periodic leg movement (PLM) index was higher in patients with NMOSD than in healthy controls (20 vs 2, p = 0.0457). Surprisingly, 77% of the patients with PLM manifested infratentorial lesions.ConclusionsSleep architecture was markedly disrupted in patients with NMOSD. Surveillance of nocturnal symptoms and adequate symptomatic control are expected to improve the quality of life of patients with NMOSD.

| S-EPMC4405292 | biostudies-literature

Neuromyelitis Optica Spectrum Disorder Presenting with Pseudoathetosis.

Project description: Not available

| S-EPMC5765249 | biostudies-literature

Current and emerging therapeutics for neuromyelitis optica spectrum disorder: Relevance to the COVID-19 pandemic.

Project description:Neuromyelitis optica spectrum disorder (NMOSD) can lead to immobility and bulbar weakness. This, in addition to the older age of onset and the higher rate of hospitalization compared to multiple sclerosis, makes this patient group a potential target for complicated COVID-19 infection. Moreover, many of the commonly used preventive therapies for NMOSD are cell-depleting immunouppsressants with increased risk of viral and bacterial infections. The emergence of several new NMOSD therapeutics, including immune-modulating agents, concurrently with the worldwide spread of the COVID-19 global pandemic call for careful therapeutic planning and add to the complexity of NMOSD management. Altering the common therapeutic approach to NMOSD during the pandemic may be necessary to balance both efficacy and safety of treatment. Selection of preventive therapy should take in consideration the viral exposure risk related to the route and frequency of administration and, most importantly, the immunological properties of each therapeutic agent and its potential impact on the risk of SARS-CoV-2 susceptibility and severity of infection. The impact of the therapeutic agent on the immune response against the future SARS-CoV-2 vaccine should also be considered in the clinical decision-making. In this review, we will discuss the immune response against SARS-CoV-2 and evaluate the potential impact of the current and emerging NMOSD therapeutics on infection risk, infection severity, and future SARS-CoV-2 vaccination. We propose a therapeutic approach to NMOSD during the COVID-19 pandemic based on analysis of the mechanism of action, route of administration, and side effect profile of each therapeutic agent.

| S-EPMC7265855 | biostudies-literature

ATP mediates neuropathic pain of neuromyelitis optica spectrum disorder via microglial activation

Project description:Intractable neuropathic pain is recognized as a common symptom of neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism of NMOSD pain remains to be elucidated. Here, we established NMOSD pain model by injecting anti-AQP4 recombinant autoantibodies (AQP4-Ab) generated from NMOSD patient’s plasmablasts into rat spinal cords and confirmed the development of mechanical allodynia. AQP4-Ab mediated extracellular ATP release from astrocytes and pharmacological inhibition of ATP receptor reversed mechanical allodynia in NMOSD pain model. Furthermore, transcriptome analysis revealed microglia activation and IL-1β elevation in NMOSD spinal cord. Inhibition of microglia activation and neutralization of IL-1β also attenuated neuropathic pain in NMOSD rat model. In addition, the human CSF ATP concentration was significantly higher in the acute and remission phase of NMOSD than in multiple sclerosis and other neurological disorder patients. These findings indicate ATP, microglial activation and IL-1β secretion orchestrates the pathogenesis of NMOSD neuropathic pain.

2021-08-24 | GSE150598 | GEO

Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism.

Project description:Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B-cells, is approved to treat aquaporin 4 (AQP4) IgG-seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III-A (FCGR3A) receptors on natural killer cells to maximize antibody-dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG-binding affinity and reduce rituximab (anti-CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab-treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

| S-EPMC10723240 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data