COVID-19 Clinical Trials and Expanded Access

The primary objective of this multi-center study is to clarify the value of a CRP measurement for triage of patients initially presenting with light symptoms of the COVID-19 infection. Current recommendations of management of COVID-19 include large-scale tests for virus. Such tests reveal whether an individual is infected with the virus, however, the demonstration of virus per se has no prognostic value for the ensuing course of the COVID-19 disease. Publications of possible treatments strategies increase exponentially, while evidence of triage of the affected individuals is mainly based on the level of pulmonary affection as measured by the Oxygen saturation. To inform decision making for which patients are to be hospitalized due to risk of developing more severe affection, this study addresses the question, whether triage may be performed with the aid of a simple CRP measurement.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the novel coronavirus disease 2019 (COVID-19) pandemic. Among COVID-19 complications, in-hospital cardiac arrest (IHCA) was reported with a very poor outcome in a retrospective single-center study (0,7% of 30 days survival with good neurological outcome among IHCA patients with a resuscitation attempt), related to its natural course and management. The incidence of unexpected in-ICU cardiac arrest (ICUCA) due to COVID-19 is still unknown. Additionally, outcome of COVID-19 patients admitted in ICU for an out-of-hospital cardiac arrest (OHCA) is also undescribed. The objective this study is : - to report the incidence of ICUCA among patients hospitalized in French ICU for COVID-19. - to report morbidity and mortality among COVID-19 patients admitted alive in ICU for an OHCA or an IHCA. The secondary objective is to assess outcome and identify risk factors of ICUCA occurrence among patients admitted for COVID-19.

The exceedingly high mortality rates of severe and critical COVID-19 warrant the identification and evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. Based on preclinical data from this institution and others, the investigators hypothesize that PI3K inhibition with duvelisib could potentially quell aberrant hyperactivtation of the innate immune system, preferentially polarize macrophages, reduce pulmonary inflammation, and limit viral persistence, thereby improving patient outcomes.

Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19

Reports of acute pulmonary embolism (APE) associated with COVID-19 have emerged in the literature. For example, Chen et al. described 25 pulmonary CT angiograms examinations from 1008 COVID-19 patients; 10 were positive for pulmonary embolism mostly as segmental or sub-segmental APE. Case reports of APE in Covid-19 patients have been published. Cui et al. found an incidence of deep venous thrombosis in intensive care unit (ICU) patients with severe Covid-19 pneumonia near to 25% (20/81), however without any correlation with potential APE. Despite these initial reports, it is not clear whether APE is more frequent in Covid-19 patients or if the association is just random. In favor of the former, D-dimer levels have been reported as elevated in patients with Covid-19 by two studies, and it has been suggested an independent association between the severity of the disease and the level of D-dimer. Finally, Tang et al. showed that anticoagulant therapy is associated with a decreased mortality at Day-28 in severe Covid-19 patients, in favor of a possible associated coagulopathy. The purpose of this study is to describe the rate of pulmonary embolus in patients classified as COVID-19 infection and who underwent chest CT angiography. The purpose of this study is to describe the rate of pulmonary embolus in patients classified as COVID-19 infection and who underwent chest CT angiography.

Online Distance Learning (ODL) is an educational delivery system that helps students to join in an educational opportunity without physically existing in the same setting as the teacher. Online learning is known as the education that takes place over the Internet, often referred to as e-Learning, web-based training (WBT), distance learning, or asynchronous learning. When learners participate in an online learning course at different times, it is known as asynchronous learning. online learning involves the umbrella term for any learning that takes place across distance and not in a traditional classroom. WHO recommends Implement social distancing practices that may include; Staggering the beginning and end of the school day and Use of online/e-learning strategies? The coronavirus pandemic has changed how millions around the globe are educated. new shifts in education approaches could widen equality gaps. As of March 13, the Organization for Economic Co-operation estimated that over 421 million students are affected due to school closures announced or implemented in 39 countries. Most faculties in affected areas are finding stop-gap solutions to continue teaching, but the quality of learning is heavily dependent on the level and quality of digital access. Therefore, the current study aimed to assess Nursing students' perception and achievement regarding unplanned shifting the Traditional Classroom-Based to Online Distance Learning as a result of (COVID-19) social distancing measures. H1: Learning perception is lower for nursing students who learned by unplanned Online Distance Learning (μ1) than for those who learned by Traditional Classroom-Based learning (μ2), (H1: μ1 < μ2). H1: Scholar achievement is greater for nursing students who learned by Traditional Classroom-Based learning (μ1) than for those who learned by unplanned Online Distance Learning (μ2), (H1: μ1 > μ2). A quasi-experimental research design will be utilized in the current study with a comparative approach. A purposive sample of adult male and female bachelor's students of nursing will be asked to participate in the current study. Three tools will be adopted to collect data relevant to the current study. 1. A brief demographic self-administrated questionnaire 2. Students' Learning Perception Questionnaire (SLPQ), 3. Modified McVay's Readiness for Online Learning Questionnaire

Worldwide observational studies indicate a significant prothrombogenic effect associated with SARS-CoV-2 infection with a high incidence of venous thromboembolism (VTE), notably life-threatening pulmonary embolism. According to recommendations for acute medical illnesses, all COVID-19 hospitalized patients should be given VTE prophylaxis such as a low molecular weight heparin (LMWH). A standard prophylactic dose (eg. Enoxaparin 4000IU once daily) could be insufficient in obese patients and VTE has been reported in patients treated with a standard prophylactic dose. In COVID-19 patients, guidelines from several international societies confirm the existence of an hypercoagulability and the importance of thromboprophylaxis but the "optimal dose is unknown" and comparative studies are needed. In view of these elements, carrying out a trial comparing various therapeutic strategies for the prevention of VTE in hospitalized patients with COVID-19 constitutes a health emergency. Thus, we hypothesize that an increased prophylactic dose of weight-adjusted LMWH would be greater than a lower prophylactic dose of LMWH to reduce the risk of life-threatening VTE in hospitalized patients. The benefit-risk balance of this increase dose will be carefully evaluated because of bleeding complications favored by possible renal / hepatic dysfunctions, drug interactions or invasive procedures in COVID-19 patients. This multicenter randomized (1:1) open-label controlled trial will randomize hospitalized adults with COVID-19 infection to weight-adjusted prophylactic dose vs. lower prophylactic dose of LMWH.

COVID-19 has a big impact on individuals and society as a whole. Especially persons with (multiple) comorbidities such as stroke are affected. The impact of COVID-19 on stroke rehabilitation delivery and stroke patients' functioning is unclear.

Endothelial injury as a consequence of SARS-CoV-2 infection leads to a dysregulated host inflammatory response and activation of coagulation pathways. Macro- and micro-vascular thrombosis may contribute to morbidity, organ failure, and death. Therapeutic anticoagulation with heparin may improve clinical outcomes in patients with COVID-19 through anti-thrombotic, anti-inflammatory, and anti-viral activities of heparins. This pragmatic, Bayesian adaptive randomized controlled trial will determine whether therapeutic anticoagulation with heparin (subcutaneous low molecular weight heparin or intravenous unfractionated heparin) versus usual care reduces the need for intubation or death in hospitalized patients with COVID-19. The trial uses an adaptive design which was chosen to overcome limitations in available data to inform a priori estimation of event rates and possible effect sizes. The adaptive design also includes response-adaptive randomization based on baseline D-dimer level, probing for differential efficacy across subgroups defined based on initial D-dimer level. This Bayesian adaptive randomized trial will stop at a conclusion 1) when the posterior probability that the proportional odds ratio is greater than 1.0 reaches 99% (definition of benefit); 2) when the posterior probability that the proportional odds ratio is greater than 1.2 is less than 10% (definition of futility) or; 3) when the posterior probability that the proportional odds ratio is less than 1.0 is greater than 90% (definition of harm). The trial will enroll a maximum of 3,000 patients, although in many simulations the trial may require fewer patients. The trial is strategically aligned with the international REMAP-CAP/COVID platform trial to accelerate evidence generation.

Background: The COVID-19 pandemic challenges the available hospital capacity, and this will be augmented by absenteeism of healthcare workers (HCW). HCW are at high risk, currently HCW constitute 20% of all the COVID-19 cases in Denmark. Strategies to prevent absenteeism of HCW are urgently needed. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other infections; significant reductions in morbidity and mortality have been reported, and a plausible immunological mechanism has been identified. We hypothesize that BCG vaccination can reduce HCW absenteeism during the COVID-19 pandemic. Primary objective: To reduce absenteeism among HCW with direct patient contacts during the COVID-19 epidemic. Secondary objective: To reduce the number of HCW that are infected with SARS-CoV-2 during the COVID-19 epidemic and to reduce the number of hospital admissions amongst HCW with direct patient contacts during the COVID-19 epidemic. Study design: A multi-center randomized placebo controlled trial. Study population: 1500 HCW with direct patient contacts; defined as nurses, physicians and other medical staff working at emergency rooms and wards where COVID-infected patients are treated. Intervention: Participants will be randomized 1:1 to intradermal administration of a standard dose of BCG vaccine or placebo (saline). Main study parameters/endpoints: Primary endpoint: Number of days of (unplanned) absenteeism for any reason. Secondary endpoints: Number of days of (unplanned) absenteeism because of documented COVID infection. Cumulative incidence of hospital admissions. Risk for participants and impact: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. The objective of this trial is to evaluate the potential beneficial effects of BCG vaccination through a lower work absenteeism rate of HCW and/or a mitigated clinical course of COVID infection.