ABSTRACT
Background: Coagulopathy and inflammation are hallmarks of COVID-19 and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19. Mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood. Aim(s): In this study, we aimed to investigate a possible role of NETs-driven coagulation factor XII (FXII) activation in COVID-19- related thrombo-inflammation. Method(s): We performed comprehensive proteomics and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We compared FXII and DNase1 activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced FXII activation using a chromogenic substrate assay. Result(s): FXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients over controls. Active FXII (FXIIa) was increased in plasma of COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII activation in COVID-19. Accumulation of NETs in COVID-19 was at least in parts due to impaired DNA clearance by extracellular DNases. In plasma from COVID-19 patients, DNase1 substitution improved NET dissolution and reduced FXII activation in vitro. Conclusion(s): Collectively, our study shows that the NETs/FXIIa axis contributes to procoagulant and proinflammatory reactions in COVID-19. Targeting NETs and FXIIa may offer a potential therapeutic strategy for interfering with the COVID-19 lung pathology.
ABSTRACT
The unexpected digital transformation that was forced due to COVID-19 found many citizens and organizations unprepared to deal with the relevant technological advances and the cyber threat landscape. This outcome highlighted once more the cybersecurity skills shortage and the necessity to address this gap. A solution to this, is to consider a multidisciplinary cybersecurity workforce with professionals originating from different backgrounds, beyond the traditional ones such as computing and IT. To be able to engage people though, they need to be aware of the possibilities that exist in cybersecurity for those that originate from non-traditional disciplines. Moreover, cybersecurity professionals need to be aware of the added value when collaborating with these professionals. These are aspects that need to be extensively investigated to provide insights to academia and industry, to develop education and training curricula towards building a multidisciplinary cybersecurity workforce. This paper investigated these aspects in a Further Education and Higher Education College in the UK, where 88 students from 5 disciplines were surveyed, providing valuable observations as to the interest of students, and future professionals, to work in cybersecurity industry and their perception on the subject disciplines relevant to cybersecurity jobs. © 2021, IFIP International Federation for Information Processing.