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  1. Article ; Online: Histomorphological patterns of regional lymph nodes in COVID-19 lungs.

    Haslbauer, Jasmin D / Matter, Matthias S / Stalder, Anna K / Tzankov, Alexandar

    Der Pathologe

    2021  Volume 42, Issue Suppl 1, Page(s) 89–97

    Abstract: Background: A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, ...

    Title translation Reaktionsmuster der lokoregionären Lymphknoten im Abflussgebiet von COVID-19-Lungen.
    Abstract Background: A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, and aberrant antigen presentation.
    Objectives: To understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed.
    Materials and methods: Lymph nodes from the cervical, mediastinal, and hilar regions were extracted from autopsies of patients with lethal COVID-19 (n = 20). Histomorphological characteristics, SARS-CoV‑2 qRT-PCR, and gene expression profiling on common genes involved in immunologic response were analyzed.
    Results: Lymph nodes displayed moderate to severe capillary stasis and edema, an increased presence of extrafollicular plasmablasts, mild to moderate plasmacytosis, a dominant population of CD8
    Conclusions: Taken together, our findings imply a dysregulated immune response in lethal COVID-19. The absence/hypoplasia of germinal centers and increased presence of plasmablasts implies a transient B‑cell response, implying an impaired development of long-term immunity against SARS-CoV‑2 in such occasions.
    MeSH term(s) CD8-Positive T-Lymphocytes ; COVID-19 ; Humans ; Lung ; Lymph Nodes ; SARS-CoV-2
    Language English
    Publishing date 2021-05-05
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 135954-x
    ISSN 1432-1963 ; 0172-8113
    ISSN (online) 1432-1963
    ISSN 0172-8113
    DOI 10.1007/s00292-021-00945-6
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    Zs.A 1543: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  2. Article ; Online: Reaktionsmuster der lokoregionären Lymphknoten im Abflussgebiet von COVID-19-Lungen.

    Haslbauer, Jasmin D / Matter, Matthias S / Stalder, Anna K / Tzankov, Alexandar

    Der Pathologe

    2021  Volume 42, Issue 2, Page(s) 188–196

    Abstract: Background: A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, ...

    Title translation Histomorphological patterns of regional lymph nodes in COVID-19 lungs.
    Abstract Background: A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, and aberrant antigen presentation.
    Objectives: To understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed.
    Materials and methods: Lymph nodes from the cervical, mediastinal, and hilar regions were extracted from autopsies of patients with lethal COVID-19 (n = 20). Histomorphological characteristics, SARS-CoV‑2 qRT-PCR, and gene expression profiling on common genes involved in immunologic response were analyzed.
    Results: Lymph nodes displayed moderate to severe capillary stasis and edema, an increased presence of extrafollicular plasmablasts, mild to moderate plasmacytosis, a dominant population of CD8
    Conclusions: Taken together, our findings imply a dysregulated immune response in lethal COVID-19. The absence/hypoplasia of germinal centers and increased presence of plasmablasts implies a transient B‑cell response, implying an impaired development of long-term immunity against SARS-CoV‑2 in such occasions.
    MeSH term(s) CD8-Positive T-Lymphocytes ; COVID-19 ; Humans ; Lung ; Lymph Nodes ; SARS-CoV-2
    Language German
    Publishing date 2021-02-11
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 135954-x
    ISSN 1432-1963 ; 0172-8113
    ISSN (online) 1432-1963
    ISSN 0172-8113
    DOI 10.1007/s00292-021-00914-z
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    Zs.A 1543: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  3. Article ; Online: Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series.

    Haslbauer, Jasmin D / Savic Prince, Spasenija / Stalder, Anna K / Matter, Matthias S / Zinner, Carl P / Jahn, Kathleen / Obermann, Ellen / Hanke, Jasmin / Leuzinger, Karoline / Hirsch, Hans H / Tzankov, Alexandar

    Pathobiology : journal of immunopathology, molecular and cellular biology

    2023  Volume 91, Issue 2, Page(s) 158–168

    Abstract: Background: Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce.: Objectives: This case series seeks to characterize the intra-alveolar immunopathology of COVID-19.: Method: BALs were performed on 14 ... ...

    Abstract Background: Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce.
    Objectives: This case series seeks to characterize the intra-alveolar immunopathology of COVID-19.
    Method: BALs were performed on 14 patients (5 COVID-19, of which 3 mild and 2 largely asymptomatic, 9 controls). Controls included asthma (n = 1), unremarkable BALs (n = 3), infections with respiratory syncytial virus (n = 1), influenza B (n = 1), and infections with other coronaviruses (n = 3). SARS-CoV-2 RNA load was measured by quantitative nucleic acid testing, while the detection of other pathogens was performed by immunofluorescence or multiplex NAT.
    Results: Gene expression profiling showed 71 significantly downregulated and 5 upregulated transcripts in SARS-CoV-2-positive lavages versus controls. Downregulated transcripts included genes involved in macrophage development, polarization, and crosstalk (LGALS3, MARCO, ERG2, BTK, RAC1, CD83), and genes involved in chemokine signaling and immunometabolism (NUPR1, CEBPB, CEBPA, PECAM1, CCL18, PPARG, ALOX5, ALOX5AP). Upregulated transcripts featured genes involved in NK-T cell signaling (GZMA, GZMH, GNLY, PRF1, CD3G). Patients with mild COVID-19 showed a significant upregulation of genes involved in blood mononuclear cell/leukocyte function (G0S2, ANXA6, FCGR2B, ADORA3), coagulation (von Willebrand factor [VWF]), interferon response (IFRD1, IL12RB2), and a zinc metalloprotease elevated in asthma (CPA3) compared to asymptomatic cases. In-silico comparison of the 5 COVID-19 BAL cases to a published cohort of lethal COVID-19 showed a significant upregulation of "antigen processing and presentation" and "lysosome" pathways in lethal cases.
    Conclusions: These data underscore the heterogeneity of immune response in COVID-19. Further studies with a larger dataset are required to gain a better understanding of the hallmarks of SARS-CoV-2 immunological response.
    MeSH term(s) Humans ; COVID-19/genetics ; SARS-CoV-2 ; RNA, Viral ; Bronchoalveolar Lavage ; Asthma ; Transcriptome
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2023-07-25
    Publishing country Switzerland
    Document type News
    ZDB-ID 1022703-9
    ISSN 1423-0291 ; 1015-2008
    ISSN (online) 1423-0291
    ISSN 1015-2008
    DOI 10.1159/000532057
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  4. Article ; Online: Neutrophil Extracellular Traps in Fatal COVID-19-Associated Lung Injury.

    Obermayer, Astrid / Jakob, Lisa-Maria / Haslbauer, Jasmin D / Matter, Matthias S / Tzankov, Alexandar / Stoiber, Walter

    Disease markers

    2021  Volume 2021, Page(s) 5566826

    Abstract: An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a ...

    Abstract An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a central factor influencing the pathophysiology and clinical presentation of severe COVID-19. A growing number of serological and morphological evidence has added to this assumption, also in regard to potential treatment options. In this study, we used immunohistochemistry and histochemistry to trace NETs and their molecular markers in autopsy lung tissue from seven COVID-19 patients. Quantification of key immunomorphological features enabled comparison with non-COVID-19 diffuse alveolar damage. Our results strengthen and extend recent findings, confirming that NETs are abundantly present in seriously damaged COVID-19 lung tissue, especially in association with microthrombi of the alveolar capillaries. In addition, we provide evidence that low-density neutrophils (LDNs), which are especially prone to NETosis, contribute substantially to COVID-19-associated lung damage in general and vascular blockages in particular.
    MeSH term(s) Aged ; Aged, 80 and over ; Antigens, CD/metabolism ; Autopsy ; COVID-19/pathology ; Cell Adhesion Molecules/metabolism ; Extracellular Traps/virology ; Female ; GPI-Linked Proteins/metabolism ; Humans ; Immunohistochemistry ; Lung/pathology ; Lung/virology ; Lung Injury/pathology ; Lung Injury/virology ; Male ; Neutrophils/metabolism ; Neutrophils/pathology ; Neutrophils/virology ; Peroxidase/metabolism
    Chemical Substances Antigens, CD ; CEACAM8 protein, human ; Cell Adhesion Molecules ; GPI-Linked Proteins ; Peroxidase (EC 1.11.1.7)
    Language English
    Publishing date 2021-07-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604951-5
    ISSN 1875-8630 ; 0278-0240
    ISSN (online) 1875-8630
    ISSN 0278-0240
    DOI 10.1155/2021/5566826
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    Zs.A 1856: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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    Einzelsignatur: Show issues

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  5. Article ; Online: Von Willebrand factor and the thrombophilia of severe COVID-19:

    van den Berg, Jana / Haslbauer, Jasmin D / Stalder, Anna K / Romanens, Anna / Mertz, Kirsten D / Studt, Jan-Dirk / Siegemund, Martin / Buser, Andreas / Holbro, Andreas / Tzankov, Alexandar

    Research and practice in thrombosis and haemostasis

    2023  Volume 7, Issue 4, Page(s) 100182

    Abstract: Background: COVID-19 is accompanied by a hypercoagulable state and characterized by microvascular and macrovascular thrombotic complications. In plasma samples from patients with COVID-19, von Willebrand factor (VWF) levels are highly elevated and ... ...

    Abstract Background: COVID-19 is accompanied by a hypercoagulable state and characterized by microvascular and macrovascular thrombotic complications. In plasma samples from patients with COVID-19, von Willebrand factor (VWF) levels are highly elevated and predictive of adverse outcomes, especially mortality. Yet, VWF is usually not included in routine coagulation analyses, and histologic evidence of its involvement in thrombus formation is lacking.
    Objectives: To determine whether VWF, an acute-phase protein, is a bystander, ie, a biomarker of endothelial dysfunction, or a causal factor in the pathogenesis of COVID-19.
    Methods: We compared autopsy samples from 28 patients with lethal COVID-19 to those from matched controls and systematically assessed for VWF and platelets by immunohistochemistry. The control group comprised 24 lungs, 23 lymph nodes, and 9 hearts and did not differ significantly from the COVID-19 group in age, sex, body mass index (BMI), blood group, or anticoagulant use.
    Results: In lungs, assessed for platelets by immunohistochemistry for CD42b, microthrombi were more frequent in patients with COVID-19 (10/28 [36%] vs 2/24 [8%];
    Conclusion: We provide
    Language English
    Publishing date 2023-05-18
    Publishing country United States
    Document type Journal Article
    ISSN 2475-0379
    ISSN (online) 2475-0379
    DOI 10.1016/j.rpth.2023.100182
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  6. Article ; Online: Correlation between structural heart disease and cardiac SARS-CoV-2 manifestations.

    Nägele, Felix / Graber, Michael / Hirsch, Jakob / Pölzl, Leo / Sahanic, Sabina / Fiegl, Manuel / Hau, Dominik / Engler, Clemens / Lechner, Sophia / Stalder, Anna Katharina / Mertz, Kirsten D / Haslbauer, Jasmin D / Tzankov, Alexandar / Grimm, Michael / Tancevski, Ivan / Holfeld, Johannes / Gollmann-Tepeköylü, Can

    Communications medicine

    2022  Volume 2, Issue 1, Page(s) 142

    Language English
    Publishing date 2022-11-11
    Publishing country England
    Document type Journal Article
    ISSN 2730-664X
    ISSN (online) 2730-664X
    DOI 10.1038/s43856-022-00204-6
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  7. Article ; Online: Neutrophil Extracellular Traps in Fatal COVID-19-Associated Lung Injury

    Astrid Obermayer / Lisa-Maria Jakob / Jasmin D. Haslbauer / Matthias S. Matter / Alexandar Tzankov / Walter Stoiber

    Disease Markers, Vol

    2021  Volume 2021

    Abstract: An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a ...

    Abstract An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a central factor influencing the pathophysiology and clinical presentation of severe COVID-19. A growing number of serological and morphological evidence has added to this assumption, also in regard to potential treatment options. In this study, we used immunohistochemistry and histochemistry to trace NETs and their molecular markers in autopsy lung tissue from seven COVID-19 patients. Quantification of key immunomorphological features enabled comparison with non-COVID-19 diffuse alveolar damage. Our results strengthen and extend recent findings, confirming that NETs are abundantly present in seriously damaged COVID-19 lung tissue, especially in association with microthrombi of the alveolar capillaries. In addition, we provide evidence that low-density neutrophils (LDNs), which are especially prone to NETosis, contribute substantially to COVID-19-associated lung damage in general and vascular blockages in particular.
    Keywords Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Genomic Landscape of Hodgkin Lymphoma.

    Brune, Magdalena M / Juskevicius, Darius / Haslbauer, Jasmin / Dirnhofer, Stefan / Tzankov, Alexandar

    Cancers

    2021  Volume 13, Issue 4

    Abstract: Background: Hodgkin lymphoma (HL) is predominantly composed of reactive, non-neoplastic cells surrounding scarcely distributed tumor cells, that is, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. This scarcity impeded ... ...

    Abstract Background: Hodgkin lymphoma (HL) is predominantly composed of reactive, non-neoplastic cells surrounding scarcely distributed tumor cells, that is, so-called Hodgkin and Reed-Sternberg (HRS) or lymphocyte predominant (LP) cells. This scarcity impeded the analysis of the tumor cell genomes for a long time, but recently developed methods (especially laser capture microdissection, flow cytometry/fluorescence-activated cell sorting) facilitated molecular investigation, elucidating the pathophysiological principles of "Hodgkin lymphomagenesis".
    Methods: We reviewed the relevant literature of the last three decades focusing on the genomic landscape of classic and nodular lymphocyte predominant HL (NLPHL) and summarized molecular cornerstones.
    Results: Firstly, the malignant cells of HL evade the immune system by altered expression of
    Conclusion: The blueprint of HL genomics has been laid, paving the way for future investigations into its complex pathophysiology.
    Language English
    Publishing date 2021-02-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13040682
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  9. Article ; Online: Vascular Damage, Thromboinflammation, Plasmablast Activation, T-Cell Dysregulation and Pathological Histiocytic Response in Pulmonary Draining Lymph Nodes of COVID-19.

    Haslbauer, Jasmin D / Zinner, Carl / Stalder, Anna K / Schneeberger, Jan / Menter, Thomas / Bassetti, Stefano / Mertz, Kirsten D / Went, Philip / Matter, Matthias S / Tzankov, Alexandar

    Frontiers in immunology

    2021  Volume 12, Page(s) 763098

    Abstract: Although initial immunophenotypical studies on peripheral blood and bronchoalveolar lavage samples have provided a glimpse into the immunopathology of COVID-19, analyses of pulmonary draining lymph nodes are currently scarce. 22 lethal COVID-19 cases and ...

    Abstract Although initial immunophenotypical studies on peripheral blood and bronchoalveolar lavage samples have provided a glimpse into the immunopathology of COVID-19, analyses of pulmonary draining lymph nodes are currently scarce. 22 lethal COVID-19 cases and 28 controls were enrolled in this study. Pulmonary draining lymph nodes (mediastinal, tracheal, peribronchial) were collected at autopsy. Control lymph nodes were selected from a range of histomorphological sequelae [unremarkable histology, infectious mononucleosis, follicular hyperplasia, non-SARS related HLH, extrafollicular plasmablast activation, non-SARS related diffuse alveolar damage (DAD), pneumonia]. Samples were mounted on a tissue microarray and underwent immunohistochemical staining for a selection of immunological markers and
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; COVID-19/immunology ; COVID-19/pathology ; Cohort Studies ; Female ; Humans ; Lung ; Lymph Nodes/immunology ; Lymph Nodes/pathology ; Macrophage Activation/immunology ; Male ; Middle Aged ; SARS-CoV-2 ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology ; Thromboinflammation/immunology ; Thromboinflammation/pathology ; Thromboinflammation/virology
    Language English
    Publishing date 2021-12-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.763098
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  10. Article ; Online: Characterisation of cardiac pathology in 23 autopsies of lethal COVID-19.

    Haslbauer, Jasmin D / Tzankov, Alexandar / Mertz, Kirsten D / Schwab, Nathalie / Nienhold, Ronny / Twerenbold, Raphael / Leibundgut, Gregor / Stalder, Anna K / Matter, Matthias / Glatz, Katharina

    The journal of pathology. Clinical research

    2021  Volume 7, Issue 4, Page(s) 326–337

    Abstract: While coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, pathophysiological changes of the cardiovascular system remain to be elucidated. We performed a retrospective cardiopathological analysis of the heart and vasculature from ...

    Abstract While coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, pathophysiological changes of the cardiovascular system remain to be elucidated. We performed a retrospective cardiopathological analysis of the heart and vasculature from 23 autopsies of COVID-19 patients, comparing the findings with control tissue. Myocardium from autopsies of COVID-19 patients was categorised into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive (n = 14) or negative (n = 9) based on the presence of viral RNA as determined by reverse transcriptase polymerase chain reaction (RT-PCR). Control tissue was selected from autopsies without COVID-19 (n = 10) with similar clinical sequelae. Histological characteristics were scored by ordinal and/or categorical grading. Five RT-PCR-positive cases underwent in situ hybridisation (ISH) for SARS-CoV-2. Patients with lethal COVID-19 infection were mostly male (78%) and had a high incidence of hypertension (91%), coronary artery disease (61%), and diabetes mellitus (48%). Patients with positive myocardial RT-PCR died earlier after hospital admission (5 versus 12 days, p < 0.001) than patients with negative RT-PCR. An increased severity of fibrin deposition, capillary dilatation, and microhaemorrhage was observed in RT-PCR-positive myocardium than in negatives and controls, with a positive correlation amongst these factors All cases with increased cardioinflammatory infiltrate, without myocyte necrosis (n = 4) or with myocarditis (n = 1), were RT-PCR negative. ISH revealed positivity of viral RNA in interstitial cells. Myocardial capillary dilatation, fibrin deposition, and microhaemorrhage may be the histomorphological correlate of COVID-19-associated coagulopathy. Increased cardioinflammation including one case of myocarditis was only detected in RT-PCR-negative hearts with significantly longer hospitalisation time. This may imply a secondary immunological response warranting further characterisation.
    MeSH term(s) Adult ; Autopsy/methods ; COVID-19/complications ; COVID-19/pathology ; COVID-19/virology ; Female ; Humans ; Male ; Middle Aged ; Myocarditis/etiology ; Myocarditis/pathology ; Myocardium/pathology ; RNA, Viral/genetics ; Respiratory System/pathology ; Respiratory System/virology ; SARS-CoV-2/pathogenicity
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2021-04-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2814357-7
    ISSN 2056-4538 ; 2056-4538
    ISSN (online) 2056-4538
    ISSN 2056-4538
    DOI 10.1002/cjp2.212
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