Derailed cytokine and immune cell networks account for organ damage and clinical severity of COVID-19 [1][2][3][4] . Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and accompanied by a senescence-associated secretory phenotype (SASP), composed of pro-inflammatory cytokines, extracellular matrix-active factors and pro-coagulatory mediators [5][6][7] . COVID-19 patients displayed markers of senescence in their airway mucosa in situ and elevated serum levels of SASP factors. Mirroring COVID-19 hallmark features such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue 1,8,9 , in vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, neutrophil extracellular trap (NET) formation as well as activation of platelets and the clotting cascade in response to supernatant of VIS cells, including SARS-CoV-2-induced senescence. Senolytics such as Navitoclax and Dasatinib/Quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-driven hamster and mouse models. Our findings mark VIS as pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest senolytic targeting of virus-infected cells as a novel treatment option against SARS-CoV-2 and perhaps other viral infections.The pandemic human pathogenic SARS-CoV-2 coronavirus causes upper respiratory infections and subsequently COVID-19 lung disease that may get further complicated by septic multi-organ failure and comes with significant mortality 10,11 . Escalating immune activation with massive cytokine release seems to drive severe COVID-19 1-3 , possibly more than the virus infection itself. Mechanisms of viral
This multicenter trial confirms and also adds to existing data, demonstrating that laboratories should expect to observe strong interferences of coagulation tests with increasing concentrations of dabigatran. This finding might become particularly important in the elderly and in patients with renal impairment as well as patients whose blood is drawn at peak levels of dabigatran.
Acquired von Willebrand syndrome (AVWS) associated with severe aortic stenosis (AS) has been frequently subclassified into a subtype 2A based on the deficiency of high-molecular-weight (HMW) multimers as it is seen in inherited von Willebrand disease (VWD) type 2A. However, the multimeric phenotype of VWD type 2A does not only include an HMW deficiency but also a decrease in intermediate-molecular-weight (IMW) multimers and an abnormal inner triplet band pattern. These additional characteristics have not been evaluated in AVWS associated with severe AS. Therefore, we recruited N ¼ 31 consecutive patients with severe AS and performed a high-resolution Western blot with densitometrical band quantification to characterize the von Willebrand factor (VWF) multimeric structure and reevaluate the AVWS subtype classification. Study patients showed an isolated HMW VWF multimer deficiency without additional abnormalities of the IMW portions and the inner triplet structure in 65%. In conclusion, the multimeric pattern of AVWS associated with severe AS does neither resemble that seen in AVWS type 2A nor that seen in inherited VWD type 2A. Therefore, a subclassification into a type 2A should not be used.
We present a case of severe fatal hepatitis in a young patient presumably triggered by two ubiquitous viral diseases which occurred in close succession. This case is unusual because of the exceptional chronological sequence of primary Epstein–Barr virus and herpes simplex virus type 1 infection causing systemic immune dysregulation associated with rapidly developing liver failure and consecutive multiorgan failure. Clinical, laboratory and histopathological findings indicated the development of secondary haemophagocytic lymphohistiocytosis triggered by these closely succeeding viral primary infections.
Biomarkers, such as troponin-T and troponin-I, are regarded as the gold standard laboratory parameter for diagnosing many cardiological diseases. These parameters have been approved for clinical use. Many cardiological guidelines recommend the analysis of troponins in the majority of cardiological disease diagnoses and to also gain prognostic information. Nonetheless, many medical circumstances could cause false troponin elevations. In this article, we focus on troponin artifacts, particularly macro-immune complex formation, as important interference factors. Therefore, we performed a literature search from 2006 to 06/2021.
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