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Brain Disease Network Analysis to Elucidate the Neurological Manifestations of COVID-19.

ABSTRACT: Although COVID-19 largely causes respiratory complications, it can also lead to various extrapulmonary manifestations resulting in higher mortality and these comorbidities are posing a challenge to the health care system. Reports indicate that 30-60% of patients with COVID-19 suffer from neurological symptoms. To understand the molecular basis of the neurologic comorbidity in COVID-19 patients, we have investigated the genetic association between COVID-19 and various brain disorders through a systems biology-based network approach and observed a remarkable resemblance. Our results showed 123 brain-related disorders associated with COVID-19 and form a high-density disease-disease network. The brain-disease-gene network revealed five highly clustered modules demonstrating a greater complexity of COVID-19 infection. Moreover, we have identified 35 hub proteins of the network which were largely involved in the protein catabolic process, cell cycle, RNA metabolic process, and nuclear transport. Perturbing these hub proteins by drug repurposing will improve the clinical conditions in comorbidity. In the near future, we assumed that in COVID-19 patients, many other neurological manifestations will likely surface. Thus, understanding the infection mechanisms of SARS-CoV-2 and associated comorbidity is a high priority to contain its short- and long-term effects on human health. Our network-based analysis strengthens the understanding of the molecular basis of the neurological manifestations observed in COVID-19 and also suggests drug for repurposing.

SUBMITTER: Prasad K

PROVIDER: S-EPMC7787249 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Brain Disease Network Analysis to Elucidate the Neurological Manifestations of COVID-19.

Prasad Kartikay K AlOmar Suliman Yousef SY Alqahtani Saeed Awad M SAM Malik Md Zubbair MZ Kumar Vijay V

Molecular neurobiology 20210106 5

Although COVID-19 largely causes respiratory complications, it can also lead to various extrapulmonary manifestations resulting in higher mortality and these comorbidities are posing a challenge to the health care system. Reports indicate that 30-60% of patients with COVID-19 suffer from neurological symptoms. To understand the molecular basis of the neurologic comorbidity in COVID-19 patients, we have investigated the genetic association between COVID-19 and various brain disorders through a sy ...[more]

PMID: 33409839

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Project description:Background and objectiveCOVID-19 neurological manifestations have been progressively recognized. Among available MRI techniques, diffusion weighted imaging (DWI) shows promise to study microstructure, inflammation, and edema. Previous DWI studies reported alterations in brain diffusivity in COVID-19 patients, as assessed by morphologic evaluation of brain DWI scans only. The aim of this study was to assess and quantify brain diffusion alterations in COVID-19 patients with neurological manifestations.Methods215 COVID-19 patients with neurological manifestations (olfactory and/or other neurological disorders) and 36 normal controls were compared and studied with DWI and T1-weighted MRI scans. MRI scans were processed by a semi-automatic processing procedure specifically developed for the purpose of this study, and the Apparent Diffusion Coefficient (ADC) was quantified in different brain tissues and individual white matter (WM) and gray matter (GM) regions. Differences in ADC values were assessed between COVID-19 patients and normal controls, as well as in the COVID-19 patient population grouped by hospitalization and neurological symptoms.ResultsAmong COVID-19 patients (median [IQR] = 52 [42 - 60] years of age, 58 % females), 91 were hospitalized and 26 needed intensive care. 84 patients had hyposmia/ageusia only, while 131 ones showed other neurological disorders. COVID-19 patients showed significantly increased ADC values in the WM and in several GM regions (p < 0.001). ADC values were significantly correlated with MRI time from disease onset (p < 0.05). Hospitalized patients showed significantly higher ADC alteration than non-hospitalized patients in all brain tissues; similarly, COVID-19 patients with neurological disorders showed significantly higher ADC values than those with olfactory loss only. ADC alteration was highest in patients with cognitive or memory disorder and in those with encephalitis or meningitis. ADC values were neither associated with the duration of hospitalization nor with the need for intensive care.ConclusionCurrent findings suggest DWI potential as a non-invasive marker of neuroinflammation in COVID-19, and the transient nature of the same. Future longitudinal studies are needed to confirm our findings.

Project description:BackgroundThe spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases.MethodsA systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients.Results44 articles were included with a pooled sample size of 13,480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2, 95% CI, 17.2 to 28.1%), taste impairment (19.6, 95% CI, 3.8 to 60.1%), smell impairment (18.3, 95% CI, 15.4 to 76.2%), headache (12.1, 95% CI, 9.1 to 15.8%), dizziness (11.3, 95% CI, 8.5 to 15.0%), and encephalopathy (9.4, 95% CI, 2.8 to 26.6%). Nearly 2.5% (95% CI, 1 to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately.ConclusionsNeurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.

Project description:Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

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Brain Disease Network Analysis to Elucidate the Neurological Manifestations of COVID-19.

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Brain Disease Network Analysis to Elucidate the Neurological Manifestations of COVID-19.

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