Von Willebrand factor and the thrombophilia of severe COVID-19: in situ evidence from autopsies

Berg, Jana Van den; Haslbauer, Jasmin D.; Stalder, Anna K.; Romanens, Anna; Mertz, Kirsten D.; Studt, Jan‐Dirk; Siegemund, Martin; Buser, Andreas; Holbro, Andreas; Tzankov, Alexandar

doi:10.1016/j.rpth.2023.100182

Cited by 6 publications

(4 citation statements)

References 69 publications

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“…Interestingly, increased levels of VWF as observed in more symptomatic (as well as in lethal) cases may be indicative of a pro-inflammatory, hypercoagulable state caused by SARS-CoV-2-mediated endothelial damage [46, 47]. The critical role of VWF in SARS-CoV-2-associated thrombophilia has previously been elucidated by our group, using data from the same autopsy cohort [15].…”

Section: Discussionmentioning

confidence: 96%

“…Control BALs were selected from a range of pulmonary findings, including asthma (n = 1), unremarkable BALs from patients investigated for a suspicious peripheral lung mass (n = 3), infections with respiratory syncytial virus (n = 1), influenza B-virus (n = 1), or other human coronaviruses (n = 3). Cases of lethal COVID-19 (n = 27) encompass a cohort of formalin-fixated and paraffin-embedded lung tissue from autopsies of patients who died of COVID-19associated respiratory failure (lethal disease, "autopsy cohort"), which had been previously published by our group [14][15][16].…”

Section: Patient Selection and Balmentioning

confidence: 99%

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Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series

Haslbauer¹,

Prince²,

Stalder³

et al. 2023

Pathobiology

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Transcriptomic data on bronchoalveolar lavage (BAL) from COVID-19 patients are currently scarce. This case series seeks to characterize the intraalveolar immunopathology of COVID-19. 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 (QNAT), while the detection of other pathogens was performed by immunofluorescence or multiplex NAT. Gene expression profiling was subsequently performed, showing 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 (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. 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.

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Section: Discussionmentioning

confidence: 96%

Section: Patient Selection and Balmentioning

confidence: 99%

Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series

Haslbauer¹,

Prince²,

Stalder³

et al. 2023

Pathobiology

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“…These control cases have been recently reported ( 12 ) and included draining pulmonary lymph nodes of 25 lethal COVID-19, 6 unremarkable (mediastinal) lymph nodes, 6 peripheral lymph nodes with follicular hyperplasia, 6 infectious mononucleosis lymphadenopathies, 5 lymphadenopathies accompanying hemophagocytic lymphohistiocytosis and 4 lymph nodes with extrafollicular plasmablast activation. Autopsies of lethal COVID-19 were performed along the first large scale report in the pandemics ( 13 – 15 ). This study has received approval by the Ethics Committee of Northwestern and Central Switzerland (ID 2020-00629).…”

Section: Methodsmentioning

confidence: 99%

Case Report: Gene expression profiling of COVID-19 vaccination-related lymphadenopathies reveals evidence of a dominantly extrafollicular immune response

Menter,

Zinner,

Berger

et al. 2023

Front. Immunol.

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mRNA-based vaccines against SARS-CoV-2 have been proven to be very efficient in preventing severe COVID-19. Temporary lymphadenopathy (LA) has been observed as a common adverse event following immunization. Here we describe a case series of three female patients with prominent local to generalized LA after SARS-CoV-2 mRNA-1273 vaccination, which led to lymph node biopsy due to the suspicion of lymphoma or metastasis. All three patients morphologically showed similar patterns of follicular hyperplasia and especially extrafollicular blast activation. Two of the three patients only had short-lasting humoral immune responses to the vaccination. Gene expression profiling (GEP) using the HTG Immune response panel revealed that all three patients clustered together and clearly differed from the GEP-patterns of COVID-19, infectious mononucleosis and non-specific follicular hyperplasia. The closest similarities were seen with lymph nodes showing extrafollicular activation of B-blasts as well as hemophagocytosis. The GEP of the vaccination-induced LA was reminiscent of an immune response with little potential of immunologic memory. mRNA-1273 vaccination-induced LA may to a certain extend reflect disordered immune response with potentially poor immunologic memory in affected individuals.

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“…Importantly, platelet activation can cause the dysregulation of NETosis, which can result in immune-mediated scattered microthrombi, hypercoagulability, and tissue damage through the vWF–NETs axis, leading to multiple organ failure and death [ 63 , 64 ]. For example, the vWF–NET axis has been noted to contribute to thrombotic complications in acute ischemic stroke and COVID-19 [ 65 ]. It has been observed that NETs cause patients with gastric cancer to have hypercoagulable platelets by upregulating the cell-surface expression of P-selectin and phosphatidylserine [ 66 , 67 ].…”

Section: Platelet Proteome In Health and Diseasesmentioning

confidence: 99%

The Perspectives of Platelet Proteomics in Health and Disease

Chaudhary,

Upadhayaya,

Kim

et al. 2024

Biomedicines

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Cardiovascular thromboembolic diseases and cancer continue to be a leading cause of death and disability worldwide. Therefore, it is crucial to advance their diagnoses and treatment in the context of individualized medicine. However, the disease specificity of the currently available markers is limited. Based on analyses of a subset of peptides and matching proteins in disease vs. healthy platelets, scientists have recently shown that focused platelet proteomics enables the quantification of disease-specific biomarkers in humans. In this review, we explored the potential of accurate platelet proteomic research, which is required to identify novel diagnostic and pharmaceutical targets by comprehending the proteome variety of healthy individuals and patients for personalized and precision medicine.

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Von Willebrand factor and the thrombophilia of severe COVID-19: in situ evidence from autopsies

Cited by 6 publications

References 69 publications

Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series

Differential Gene Expression of SARS-CoV-2 Positive Bronchoalveolar Lavages: A Case Series

Case Report: Gene expression profiling of COVID-19 vaccination-related lymphadenopathies reveals evidence of a dominantly extrafollicular immune response

The Perspectives of Platelet Proteomics in Health and Disease

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