External Validation of the 4C Mortality Score and the qSOFA for Different Variants of Concerns of SARS-CoV-2 Using Data of the NAPKON Cross-Sectoral Cohort Platform (SUEP)

Background. Numerous predictive clinical scores with varying discriminatory performance have been developed in the context of the current coronavirus disease 2019 (COVID-19) pandemic. To support clinical application, we test the transferability of the frequently applied 4C mortality score (4C score) to the German prospective Cross-Sectoral Platform (SUEP) of the National Pandemic Cohort Network (NAPKON) compared to the non COVID-19 specific quick sequential organ failure assessment score (qSOFA). Our project aims to externally validate these two scores, stratified for the most prevalent variants of concerns (VOCs) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in Germany. Methods. A total of 685 adults with polymerase chain reaction (PCR)-detected SARS-CoV-2 infection were included from NAPKON-SUEP. Patients were recruited from 11/2020 to 03/2022 at 34 university and non-university hospitals across Germany. Missing values were complemented using multiple imputation. Predictive performance for in-hospital mortality at day of baseline visit was determined by area under the curve (AUC) with 95%-confidence interval (CI) stratified by VOCs of SARS-CoV-2 (alpha, delta, omicron) (Figure 1). Figure 1: Study flow chart with inclusion criteria and methodological workflow. Results. Preliminary results suggest a high predictive performance of the 4C score for in-hospital mortality (Table 1). This applies for the overall cohort (AUC 0.813 (95%CI 0.738-0.888)) as well as the VOC-strata (alpha: AUC 0.859 (95%CI 0.748-0.970);delta: AUC 0.769 (95%CI 0.657-0.882);omicron: AUC 0.866 (95%CI 0.724-1.000)). The overall mortality rates across the defined 4C score risk groups are 0.3% (low), 3.2% (intermediate), 11.6% (high), and 49.5% (very high). The 4C score performs significantly better than the qSOFA (Chi2-test: p=0.001) and the qSOFA does not seem to be a suitable tool in this context. Table 1: Discriminatory performance of the 4C Mortality Score and the qSOFA score within the validation cohort NAPKON-SUEP stratified by the Variant of Concerns of SARS-CoV- 2. Conclusion. Despite its development in the early phase of the pandemic and improved treatment, external validation of the 4C score in NAPKON-SUEP indicates a high predictive performance for in-hospital mortality across all VOCs. However, since the qSOFA was not specifically designed for this predictive issue, it shows low discriminatory performance, as in other validation studies. Any interpretations regarding the omicron stratum are limited due to the sample size.

Making Sense of Crisis: Instructional Designers' Experiences with Emergency Remote Teaching

Following the transition to e-learning due to COVID-19, instructional designers (IDs) went into action to prepare faculty for distance education using new technologies and pedagogical approaches. The purpose of this qualitative study was to interpret how five members of an ID team at a U.S. higher education institution made sense of their experiences designing and implementing faculty-training courses to aid the emergency remote transition. Using sensemaking theory (Weick, 1988), this study explored their collective meaning-making process through collaborative multistep narrative and thematic analysis. The themes progressed on a storyline depicting their immediate action in response to the crisis, their felt emotions considering the challenges they encountered, their interpretations of collaboration and implementation, and their retrospective feelings of success. Implications of findings will contribute to continuity planning to inform future iterations of faculty-training courses as well as approaches to change and/or crisis impacting online instructional innovation within higher education. © 2022, The Online Learning Consortium. All rights reserved.

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.

Recommendations for treatment of critically ill patients with COVID-19 : Version 3 S1 guideline.

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.

Emergency support for faculty: Adherence to best practices in designing, developing, and implementing virtual training during a pandemic

COVID-19 disrupted face-to-face instruction across university campuses world-wide. As universities struggled, instructional design teams stepped in to assist. At one southeastern university in the US, an instructional design team, with support from instructional systems analysts, responded by creating online instruction for faculty and facilitating training during the summer months in 2020. Literature outlining multiple perspectives and best practices for online instruction prior to the onset of the COVID-19 pandemic is robust;however, provides little to no guidance for implementing empirically based practice during a time of worldwide crisis. Many educational institutions recognised the need to provide a timely response to ensure continuity and quality of education yet lacked a framework or model from which to follow. This mixed methods study reviews best practices for designing and implementing virtual training for faculty and determines to what extent best practices were followed for this shift during a time of crisis. The use of a survey and semi-structured interviews with the instructional design team and instructional systems analysts resulted in four themes: Prioritising faculty needs, responsiveness to faculty, lack of time, and difficulties collaborating across departments. Alignment to pre-pandemic best practice literature is provided to demonstrate the response of one university to the pandemic. Implications for instructional design teams and future research directions are presented. Practitioner Notes 1. Instructional design teams are well-equipped to assist academics with creating and implementing online and hybrid delivery modalities;however, they are less likely to be prepared to assist on a large scale and with a short timeframe. 2. Prior to the pandemic, instructional design teams worked to adhere to evidence-based best practices in order to meet the needs of their universities but lacked time during the worldwide crisis. 3. Instructional design teams may benefit from having an instructional continuity plan in place, that is revisited and updated frequently, in preparation for emergency remote teaching situations. 4. Higher Education Institutes would benefit from investigating their own instructional design practices in emergency remote teaching. © 2022, University of Wollongong. All rights reserved.