Dataset Information

Viral Metagenomics on Cerebrospinal Fluid.

ABSTRACT: Identifying the causative pathogen in central nervous system (CNS) infections is crucial for patient management and prognosis. Many viruses can cause CNS infections, yet screening for each individually is costly and time-consuming. Most metagenomic assays can theoretically detect all pathogens, but often fail to detect viruses because of their small genome and low viral load. Viral metagenomics overcomes this by enrichment of the viral genomic content in a sample. VIDISCA-NGS is one of the available workflows for viral metagenomics, which requires only a small input volume and allows multiplexing of multiple samples per run. The performance of VIDISCA-NGS was tested on 45 cerebrospinal fluid (CSF) samples from patients with suspected CNS infections in which a virus was identified and quantified by polymerase chain reaction. Eighteen were positive for an RNA virus, and 34 for a herpesvirus. VIDISCA-NGS detected all RNA viruses with a viral load >2 × 10⁴ RNA copies/mL (n = 6) and 8 of 12 of the remaining low load samples. Only one herpesvirus was identified by VIDISCA-NGS, however, when withholding a DNase treatment, 11 of 18 samples with a herpesvirus load >10⁴ DNA copies/mL were detected. Our results indicate that VIDISCA-NGS has the capacity to detect low load RNA viruses in CSF. Herpesvirus DNA in clinical samples is probably non-encapsidated and therefore difficult to detect by VIDISCA-NGS.

SUBMITTER: Edridge AWD

PROVIDER: S-EPMC6562652 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Viral Metagenomics on Cerebrospinal Fluid.

Edridge Arthur W D AWD Deijs Martin M van Zeggeren Ingeborg E IE Kinsella Cormac M CM Jebbink Maarten F MF Bakker Margreet M van de Beek Diederik D Brouwer Matthijs C MC van der Hoek Lia L

Genes 20190430 5

Identifying the causative pathogen in central nervous system (CNS) infections is crucial for patient management and prognosis. Many viruses can cause CNS infections, yet screening for each individually is costly and time-consuming. Most metagenomic assays can theoretically detect all pathogens, but often fail to detect viruses because of their small genome and low viral load. Viral metagenomics overcomes this by enrichment of the viral genomic content in a sample. VIDISCA-NGS is one of the avail ...[more]

PMID: 31052348

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Project description:BackgroundNeurological manifestations are present in about one-third of COVID-19 cases, ranging from mild symptoms, such as anosmia, to more severe forms like demyelinating syndromes. Although direct invasion of the CNS has been demonstrated, the immune- mediated pathway is also described and more accepted. Even in cases where viral detection in CSF is absent, it should not rule out neuroinvasion. There are few prospective studies about neurological manifestations of COVID-19, especially with viral tests in CSF; as well there are still many questions about COVID-19 associated with neurological disease. Thus, we describe clinical and CSF findings of a prospective cohort of patients with nasal positive tests for SARS-CoV-2 and neurological involvement. We also discuss the pathogenic mechanisms related to these manifestations.Methods and findingsThis is a prospective cohort study; 27 patients were evaluated according to clinical presentation, the time interval between COVID-19 diagnosis and onset of neurological alterations, syndromic diagnosis, imaging and CSF findings. Real time polymerase chain reaction for SARS-CoV-2 genome was performed in all CSF samples. 2 RT-PCR in spinal cord fluid resulted positive in 9 (33.3%) cases, five of them had a positive swab nasal test concomitant to neurologic disease. Respiratory signs were described in 12 out 27 patients, five of them with viral detection in CSF. White cell counts in CSF were normal range in the majority of cases, except for 3 occurrences: two patients had elevated CSF WBC counts and viral detection in CSF (10 and 36 cells/mm3) and one also had elevated CSF WBC count but viral detection in CSF was negative (21cells/mm3). The observed neurological signs encompassed a diverse neurologic spectrum, including seizures, paresis, gait abnormalities, headaches, alteration in consciousness and memory or cognitive impairment. Both imaging and CSF alterations exhibited non-specific characteristics. Syndromic diagnoses included stroke, dementia or cognitive impairments, Guillain-Barré Syndrome, encephalitis, encephalomyelitis, acute flaccid palsy and optical neuritis.ConclusionsThe patients in the present study had COVID-19 and neurologic involvement including a wide range of clinical manifestations. SARS-CoV-2 was detected in one-third of CSF samples, regardless of time interval between COVID-19 diagnosis and the onset of neurological signs. These conditions encompass various pathogenic pathways and the neuroinvasion potential of SARS-CoV-2 should be more studied.

Project description:Differential diagnosis of bacterial meningitis (BM) and viral meningitis (VM) is a critical clinical challenge, as the early and accurate identification of the causative agent determines the appropriate treatment regimen and markedly improves patient outcomes. Clinical and experimental studies have demonstrated that the pathogen and the host immune response contribute to mortality and neurological sequelae. As BM is associated with the activation of an inflammatory cascade, the patterns of pro- and anti-inflammatory cytokines/chemokines (CTs/CKs) present in the cerebrospinal fluid (CSF) in response to the immune assault may be useful as sensitive markers for differentiating BM from VM. In the present study, the ability of CTs/CKs in the CSF to differentiate between BM and VM was investigated. For this, biochemical markers and CT/CK profiles were analysed in 145 CSF samples, divided into three groups: BM (n=61), VM (n=58) and the control group (C; n=26) comprising patients with meningism. The CSF concentrations of monocyte chemoattractant protein-1, interleukin (IL)-8, IL-1β, IL-6, macrophage inflammatory protein-1α (MIP-1α), epithelial-neutrophil activating peptide, IL-10, tumour necrosis factor-α (TNF-α), proteins and white blood cells were significantly higher and the CSF glucose level was significantly lower in the BM group compared with the VM and C groups (P<0.01). Correlation analysis identified 28 significant correlations between various CTs/CKs in the BM group (P<0.01), with the strongest positive correlations being for TNF-α/IL-6 (r=0.75), TNF-α/MIP-1α (r=0.69), TNF-α/IL-1β (r=0.64) and IL-1β/MIP-1α (r=0.64). To identify the optimum CT/CK patterns for predicting and classifying BM and VM, a dataset of 119 BM and VM samples was divided into training (n=90) and testing (n=29) subsets for use as input for a Random Forest (RF) machine learning algorithm. For the 29 test samples (15 BM and 14 VM), the RF algorithm correctly classified 28 samples, with 92% sensitivity and 93% specificity. The results show that the patterns of CT/CK levels in the CSF can be used to aid discrimination of BM and VM.

Dataset Information

Viral Metagenomics on Cerebrospinal Fluid.

Publications

Viral Metagenomics on Cerebrospinal Fluid.

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