Publications by authors named "Nick Neuwinger"

5 Publications

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A Matter of Caution: Coagulation Parameters in COVID-19 Do Not Differ from Patients with Ruled-Out SARS-CoV-2 Infection in the Emergency Department.

TH Open 2021 Jan 6;5(1):e43-e55. Epub 2021 Feb 6.

Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

COVID-19 (coronavirus disease 2019) patients often show excessive activation of coagulation, associated with increased risk of thrombosis. However, the diagnostic value of coagulation at initial clinical evaluation is not clear. We present an in-depth analysis of coagulation in patients presenting to the emergency department (ED) with suspected COVID-19.  = 58 patients with clinically suspected COVID-19 in the ED were enrolled.  = 17 subsequently tested positive using SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) polymerase chain reaction (PCR) swabs, while in  = 41 COVID-19 was ruled-out. We analyzed both standard and extended coagulation parameters, including thromboplastin time (INR), activated partial thromboplastin time (aPTT), antithrombin, plasminogen, plasminogen activator inhibitor-1 (PAI-1), D-dimers, and fibrinogen at admission, as well as α2-antiplasmin, activated protein C -resistance, factor V, lupus anticoagulant, protein C, protein S, and von Willebrand diagnostics. These data, as well as mortality and further laboratory parameters, were compared across groups based on COVID-19 diagnosis and severity of disease. In patients with COVID-19, we detected frequent clotting abnormalities, including D-dimers. The comparison cohort in the ED, however, showed similarly altered coagulation. Furthermore, parameters previously shown to distinguish between severe and moderate COVID-19 courses, such as platelets, plasminogen, fibrinogen, aPTT, INR, and antithrombin, as well as multiple nonroutine coagulation analytes showed no significant differences between patients with and without COVID-19 when presenting to the ED. At admission to the ED the prevalence of coagulopathy in patients with COVID-19 is high, yet comparable to the non-COVID-19 cohort presenting with respiratory symptoms. Nevertheless, coagulopathy might worsen during disease progression with the need of subsequent risk stratification.
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http://dx.doi.org/10.1055/s-0040-1722612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867413PMC
January 2021

Role of cell adhesion molecules for disease development of patients with and without COVID-19 in the emergency department.

J Infect Dis 2021 Jan 27. Epub 2021 Jan 27.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Berlin, Germany.

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http://dx.doi.org/10.1093/infdis/jiab042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928779PMC
January 2021

Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment.

Cell 2020 09 5;182(6):1419-1440.e23. Epub 2020 Aug 5.

Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL).

Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRCD11c inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DR monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.
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http://dx.doi.org/10.1016/j.cell.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405822PMC
September 2020

Underfilling of vacuum blood collection tubes leads to increased lactate dehydrogenase activity in serum and heparin plasma samples.

Clin Chem Lab Med 2020 01;58(2):213-221

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Berlin, Germany.

Background Lactate dehydrogenase (LD) activity is routinely monitored for therapeutic risk stratification of malignant diseases, but is also prone to preanalytical influences. Methods We systematically analyzed the impact of defined preanalytical conditions on the hemolysis-susceptible parameters LD, potassium (K) and hemolysis index in vacuum blood collection tubes (serum [SE], heparin plasma [HP]). Blood was collected by venipuncture from healthy volunteers. Tubes were either filled or underfilled to approximately 50%, then processed directly or stored at room temperature for 4 h. Potassium (K), sodium (Na), chloride (Cl), LD, creatine kinase (CK), total cholesterol, and indices for hemolysis, icterus, and lipemia were analyzed. Filling velocity was determined in a subset of tubes. Findings in healthy volunteers were reconfirmed in an in-patient cohort (n = 74,751) that was analyzed for plasma yield and LD data distribution. Results LD activity was higher in HP compared to SE. Underfilling led to higher LD values (SE: +21.6%; HP: +28.3%), K (SE: +4.2%; HP: +5.3%), and hemolysis index (SE: +260.8%; HP: +210.0%), while other analytes remained largely unchanged. Filling velocity of tubes was approximately 3-fold higher in the first half compared to the second half in both HP and SE collection tubes. Importantly, plasma yield also inversely correlated with LD in routine patients. By calculating reference limits, the lowest plasma yield quartile of the patient cohort displayed LD values clearly exceeding current reference recommendations. Conclusions Underfilling of tubes leads to a higher proportion of blood aspirated with high velocity and relevant elevations in LD. This finding should be considered in cases of clinically implausible elevated LD activities.
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http://dx.doi.org/10.1515/cclm-2019-0616DOI Listing
January 2020

Loss of Phosphatase and Tensin Homolog in APCs Impedes Th17-Mediated Autoimmune Encephalomyelitis.

J Immunol 2015 Sep 5;195(6):2560-70. Epub 2015 Aug 5.

Institute for Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria;

The PI3K signaling cascade in APCs has been recognized as an essential pathway to initiate, maintain, and resolve immune responses. In this study, we demonstrate that a cell type-specific loss of the PI3K antagonist phosphatase and tensin homolog (PTEN) in myeloid cells renders APCs toward a regulatory phenotype. APCs deficient for PTEN exhibit reduced activation of p38 MAPK and reduced expression of T cell-polarizing cytokines. Furthermore, PTEN deficiency leads to upregulation of markers for alternative activation, such as Arginase 1, with concomitant downregulation of inducible NO synthase in APCs in vitro and in vivo. As a result, T cell polarization was dysfunctional in PTEN(-/-) APCs, in particular affecting the Th17 cell subset. Intriguingly, mice with cell type-specific deletions of PTEN-targeting APCs were protected from experimental autoimmune encephalomyelitis, which was accompanied by a pronounced reduction of IL-17- and IL-22-producing autoreactive T cells and reduced CNS influx of classically activated monocytes/macrophages. These observations support the notion that activation of the PI3K signaling cascade promotes regulatory APC properties and suppresses pathogenic T cell polarization, thereby reducing the clinical symptoms and pathology of experimental autoimmune encephalomyelitis.
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http://dx.doi.org/10.4049/jimmunol.1402511DOI Listing
September 2015