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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333041

ABSTRACT

Abstract: Patients with COVID-19 can have a variety of neurological symptoms, but the pathomechanism of CNS involvement in COVD-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce. Here, we used mass spectrometry to study the proteome, Enzym-linkend immunoassays, semiquantitative cytokine arrays, autoantibody screening, and RNA profiling to study the neuroinflammation. We study the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n=38). Patients with herpes simplex virus encephalitis (HSVE, n=10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n=28) served as controls. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients. CSF/serum indices of interleukin-6, interleukin-16 and CXCL10 together point at an origin from these inflammatory proteins from outside the central nervous system. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly higher in those with concomitant bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, micro RNAs and t-RNA fragments being significantly differentially expressed in COVID-19 than in HSVE or controls. Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological post-COVID-19 symptoms deserves further investigation.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296283

ABSTRACT

Global healthcare systems continue to be challenged by the COVID-19 pandemic, and there is a need for clinical assays that can both help to optimize resource allocation and accelerate the development and evaluation of new therapies. Here, we present a multiplex proteomic panel assay for the assessment of disease severity and outcome prediction in COVID-19. The assay quantifies 50 peptides derived from 30 COVID-19 severity markers in a single measurement using analytical flow rate liquid chromatography and multiple reaction monitoring (LC-MRM), on equipment that is broadly available in routine and regulated analytical laboratories. We demonstrate accurate classification of COVID-19 severity in patients from two cohorts. Furthermore, the assay outperforms established risk assessments such as SOFA and APACHE II in predicting survival in a longitudinal COVID-19 cohort. The prognostic value implies its use for support of clinical decisions in settings with overstrained healthcare resources e.g. to optimally allocate resources to severely ill individuals with high chance of survival. It can furthermore be helpful for monitoring of novel therapies in clinical trials.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293571

ABSTRACT

Global healthcare systems continue to be challenged by the COVID-19 pandemic, and there is a need for clinical assays that can both help to optimize resource allocation and accelerate the development and evaluation of new therapies. Here, we present a multiplex proteomic panel assay for the assessment of disease severity and outcome prediction in COVID-19. The assay quantifies 50 peptides derived from 30 COVID-19 severity markers in a single measurement using analytical flow rate liquid chromatography and multiple reaction monitoring (LC-MRM), on equipment that is broadly available in routine and regulated analytical laboratories. We demonstrate accurate classification of COVID-19 severity in patients from two cohorts. Furthermore, the assay outperforms established risk assessments such as SOFA and APACHE II in predicting survival in a longitudinal COVID-19 cohort. The prognostic value implies its use for support of clinical decisions in settings with overstrained healthcare resources e.g. to optimally allocate resources to severely ill individuals with high chance of survival. It can furthermore be helpful for monitoring of novel therapies in clinical trials.

4.
Nat Commun ; 12(1): 4869, 2021 08 11.
Article in English | MEDLINE | ID: covidwho-1354100

ABSTRACT

In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies.


Subject(s)
COVID-19/immunology , Disease Models, Animal , Alveolar Epithelial Cells/immunology , Animals , Cricetinae , Cytokines/genetics , Cytokines/immunology , Endothelial Cells/immunology , Humans , Immunoglobulin M/immunology , Inflammation , Lung/immunology , Macrophages/immunology , Mesocricetus , Monocytes/immunology , SARS-CoV-2/immunology , Signal Transduction , T-Lymphocytes, Cytotoxic/immunology , Toll-Like Receptors/immunology
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