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Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms.

ABSTRACT: Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.

SUBMITTER: Cunningham JL

PROVIDER: S-EPMC8083780 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms.

Cunningham Janet L JL Virhammar Johan J Rönnberg Bengt B Dopico Xaquin Castro XC Kolstad Linda L Albinsson Bo B Kumlien Eva E Nääs Anja A Klang Andrea A Westman Gabriel G Zetterberg Henrik H Frithiof Robert R Lundkvist Åke Å Karlsson Hedestam Gunilla B GB Rostami Elham E

The Journal of infectious diseases 20220301 6

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated ...[more]

PMID: 33744954

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Project description:BackgroundComprehensive characterization of the metabolome in cerebrospinal fluid (CSF) and serum by Nuclear Magnetic Resonance (NMR) spectroscopy may identify biomarkers and contribute to the understanding of the pathophysiology of neurological diseases.MethodsMetabolites were determined by NMR spectroscopy in stored CSF/serum samples of 20 patients with Parkinson's disease, 25 patients with other neuro-degenerative diseases, 22 patients with cerebral ischemia, 48 patients with multiple sclerosis, and 58 control patients with normal CSF findings. The data set was analysed using descriptive and multivariate statistics, as well as machine learning models.ResultsCSF glucose and lactic acid measured by NMR spectroscopy and routine clinical chemistry showed a strong correlation between both methods (glucose, R2 = 0.87, n = 173; lactic acid, R2 = 0.74, n = 173). NMR spectroscopy detected a total of 99 metabolites; 51 in both, CSF and serum, 16 in CSF only, and 32 in serum only. CSF concentrations of some metabolites increased with age and/or decreasing blood-brain-barrier function. Metabolite detection rates were overall similar among the different disease groups. However, in two-group comparisons, absolute metabolite levels in CSF and serum discriminated between multiple sclerosis and neurodegenerative diseases (area under the curve (AUC) = 0.96), multiple sclerosis and Parkinson's disease (AUC = 0.89), and Parkinson's disease and control patients (AUC = 0.91), as demonstrated by random forest statistical models. Orthogonal partial least square discriminant analysis using absolute metabolite levels in CSF and serum furthermore permitted separation of Parkinson's disease and neurodegenerative diseases. CSF propionic acid levels were about fourfold lower in Parkinson's disease as compared to neurodegenerative diseases.ConclusionsThese findings outline the landscape of the CSF and serum metabolome in different categories of neurological diseases and identify age and blood-brain-barrier function as relevant co-factors for CSF levels of certain metabolites. Metabolome profiles as determined by NMR spectroscopy may potentially aid in differentiating groups of patients with different neurological diseases, including clinically meaningful differentiations, such as Parkinson's disease from other neurodegenerative diseases.

Project description:Serological testing is recommended to support the detection of undiagnosed coronavirus disease 2019 (COVID-19) cases. However, the performance of serological assays has not been sufficiently evaluated. Hence, the performance of six severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding antibody assays [three chemiluminescence (CLIAs) and three lateral flow immunoassays (LFIAs)] and a surrogate virus neutralization test (sVNT) was analyzed in a total of 988 serum samples comprising 389 COVID-19-positives and 599 COVID-19-negatives. The overall diagnostic sensitivities of CLIAs and LFIAs ranged from 54.2 to 56.6% and from 56.3 to 64.3%, respectively. The overall diagnostic specificities of CLIAs and LFIAs ranged from 98.2 to 99.8% and from 97.3 to 99.0%, respectively. In the symptomatic group (n = 321), the positivity rate increased by over 80% in all assays > 14 days after symptom onset. In the asymptomatic group (n = 68), the positivity rate increased by over 80% in all assays > 21 days after initial RT-PCR detection. In LFIAs, negatively interpreted trace bands accounted for the changes in test performance. Most false-positive results were weak or trace reactions and showed negative results in additional sVNT. For six binding antibody assays, the overall agreement percentages ranged from 91.0 to 97.8%. The median inhibition activity of sVNT was significantly higher in the symptomatic group than in the asymptomatic group (50.0% vs. 29.2%; p < 0.0001). The median times to seropositivity in the symptomatic group were 9.7 days for CLIA-IgG, 9.2 and 9.8 days for two CLIAs-Total (IgM + IgG), 7.7 days for LFIA-IgM, 9.2 days for LFIA-IgG, and 8.8 days for sVNT-IgG, respectively. There was a strong positive correlation between the quantitative results of the four binding antibody assays and sVNT with Spearman ρ-values ranging from 0.746 to 0.854. In particular, when using LFIAs, we recommend using more objective interpretable assays or establishing a band interpretation system for each laboratory, accompanied by observer training. We also anticipate that sVNT will play an essential role in SARS-CoV-2 antibody testing and become the practical routine neutralizing antibody assay.

Dataset Information

Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms.

Publications

Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms.

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