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
Background: Coronavirus disease 2019 (COVID-19), a disease caused by the new coronavirus (SARS-CoV-2), is a particular threat to old people. At the end of March 2020, the first and so far largest outbreak of the disease occurred in a retirement home in Hamburg. Methods: Analysis of procedures in dealing with a residential unit affected by SARS-CoV2, accommodating a risk group of 60 seniors with dementia is presented as well as a detailed presentation of post-mortem examination results of all 8 deceased tested positive for SARS-CoV2. Results: Out of 60 residents, 39 were infected by SARS-CoV2. Due to preventive procedures it was possible to stop further spreading of the infection to other residential areas. In all 8 fatal cases, the autopsy diagnosis was death due to COVID-19. Autopsies revealed all COVID-19 patients to have a fatal (broncho)pneumonia and signs of relevant pre-existing cardiac, renal and pulmonary conditions in all cases. In 75% (nâ¯= 6) of the cases a fresh venous thrombosis was found. In 66.7% (nâ¯= 4) of the cases thrombotic events were combined with peripheral pulmonary artery thromboembolisms. Conclusion: The cohort of SARS-CoV2 infected residents of a nursing home is characteristic for clinical and epidemiological features of the new coronavirus disease. Due to a centralized evaluation of all fatalities at the Institute of Legal Medicine in Hamburg, a detailed examination of all deceased positive for SARS-CoV2 was possible. Thereby, increased case fatality rates of approximately 20% could in all cases be assigned to a relevant number of pre-existing comorbidities of multiple organ systems, which was consistent with the clinical data available.
ABSTRACT
Post-mortem computed tomography (PMCT) is a rapid and noninvasive diagnostic tool for important contributions to the identification of pulmonary findings in the deceased with pneumonia, including cases of coronavirus disease 2019 (COVID-19). Although computed tomography (CT) shows a high sensitivity for pneumonia in living persons, it is relatively unspecific for COVID-19 pneumonia clinically. Typical CT findings for viral pneumonia therefore require confirmation by PCR tests (polymerase chain reaction tests), even if lung infections with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) show characteristic patterns, most frequently ground glass opacities (GGO) and a combination of GGO and air space consolidations. In the consecutive autopsy series of SARS-CoV2 deaths from Hamburg, Germany, the most frequent cause of death was and still is COVID-19 pneumonia. Typical findings were frequently found in the PMCT in SARS-CoV-2-associated deaths, which were taken into account when classifying the death as COVID-19.
ABSTRACT
Forensic medicine and pathology involve specific health risks, whereby health workers are dealing with microorganisms, cells or parasites, which are referred to as biological agents. Biological agents are divided into four categories according to § 3 of the Biological Agents Ordinance. The newly identified coronavirus, severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2) that has spread rapidly around the world is placed into category 3 of the Biological Agents Ordinance, meaning pathogens that can cause serious illnesses in humans and may pose a risk to workers. The Robert Koch Institute, the German government's central scientific institution in the field of biomedicine issued the announcement, that aerosol-producing measures (including autopsies) of SARS-CoV2 infected bodies should be avoided, despite the fact that autopsies are an important source of understanding the pathomorphological course of new diseases. The first German case of death due to a proven SARS-CoV2 infection is presented with global multifocal reticular consolidation in the post-mortem computed tomography (CT) scan, a macroscopic and microscopic viral pneumonia and viral RNA of SARS-CoV2 in pharyngeal mucosa and lung tissue.