Factor XII activation by NET accumulation aggravates COVID-19- associated pulmonary thrombo-inflammation

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.

[The first COVID-19 hotspot in a retirement home in Hamburg]. / Der erste COVID-19-Hotspot in einer Hamburger Senioreneinrichtung: Präventionskonzept, Letalität und Obduktionsbefunde.

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% (n = 6) of the cases a fresh venous thrombosis was found. In 66.7% (n = 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.

Determinants of health-related quality of life among homeless individuals during the COVID-19 pandemic.

OBJECTIVE: To clarify which variables are associated with the health-related quality of life (HRQoL) among homeless individuals during the COVID-19 pandemic. STUDY DESIGN: Cross-sectional research. METHODS: Data were taken from the Hamburg survey of homeless individuals (n = 151). HRQoL was assessed using the EQ-5D tool. More precisely, the EQ-5D-5L questionnaire was used to quantify problems in five health dimensions (i.e. mobility, self-care, usually activities, pain/discomfort, anxiety/depression), and its visual analog scale (EQ-VAS) was used to record the according self-rated health status. Explanatory variables include sex, age, education, marital status, country of origin, health insurance, and chronic alcohol consumption. RESULTS: With regard to HRQoL, most frequently, problems were reported as pain/discomfort (47.3%), followed by anxiety/depression (32.4%), mobility (29.7%), usual activities (20.7%) and self-care (4.6%). The mean EQ-VAS score was 75.34 (SD 22.23; range 1-100), and the mean EQ-5D-5L index was 0.84 (SD 0.23; range 0.32-1). Regressions showed increasing problems in mobility and self-care with higher age, whereas EQ-VAS was positively associated with younger age. Furthermore, EQ-5D-5L index was positively associated with younger age and higher education. Summarized, among this cohort, a higher age is associated with a lower HRQoL. CONCLUSION: Remarkably high EQ-VAS values and rather few problems in the five dimensions investigated here were reported among the homeless individuals during the COVID-19 pandemic particularly compared with the general population. Moreover, study findings particularly stress the link between higher age and lower HRQoL among homeless individuals. This knowledge is important to address homeless individuals at risk of poor HRQoL. Longitudinal studies are required to confirm the given findings.

COVID-19 lungs in post-mortem computed tomography.

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.

[Postmortem imaging of the lung in cases of COVID-19 deaths]. / Postmortale Bildgebung der Lunge bei COVID-19-Todesfällen.

CLINICAL/METHODOLOGICAL ISSUE: COVID-19 is a new viral disease that is associated with inflammatory pulmonary changes which can be detected in computed tomography (CT). So far postmortem CT (PMCT) has not been used as a screening instrument for the evaluation of deaths with and without autopsy. In this respect, its validity has to be proved in comparison to clinical-radiological experiences. STANDARD RADIOLOGICAL METHODS: Postmortem CT METHODICAL INNOVATIONS: So far, PMCT can be regarded as a methodological innovation that has not yet been sufficiently evaluated for pneumonia. PERFORMANCE: CT in clinical routine has a high sensitivity for pneumonia. However, to what extent postmortem artifacts are relevant to PMCT still has to be determined. ACHIEVEMENTS: There is still no standard procedure for the postmortem radiological diagnosis of COVID-19 disease. Despite postmortem artifacts, PMCT can provide valuable information about the presence of pneumonia with interstitial character, especially without autopsy. PRACTICAL RECOMMENDATIONS: PMCT is particularly useful in the assessment of suspected cases of COVID-19 pneumonia for morphological assessment in the context of monitoring deaths in the current pandemic situation.

Evidence for systematic autopsies in COVID-19 positive deceased: Case report of the first German investigated COVID-19 death.

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.