COVID-19 Clinical Trials and Expanded Access

In this study we propose to treat 560 patients with ramipril or placebo for 14 days. After an initial evaluation for COVID-19 status, medical history, and symptom assessment, patients will receive either 2.5 mg/day of ramipril or placebo. Patients' symptoms and study endpoints will be monitored at regular intervals. After 14 days, patients will undergo a laboratory assessment and an end-of-treatment follow-up visit at day 28. The primary endpoints of successful therapy will be improved survival, reductions in ICU admissions, and/or reductions in use of mechanical ventilator support.

This study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in patients with moderate COVID-19 disease.

It is supposed to monitor hypertensive patients who are infected or have clinical manifestations of COVID-19 for 1 month after the onset of the disease. Three groups will be considered: 1. receiving ACE inhibitors 2. receiving ARBs 3. receiving DIR.

The SARS-CoV2 virus causes severe or even fatal disease in a fraction of infected people. The clinical severity is based on a complicated pneumopathy with acute respiratory distress syndrome that can lead to multi-visceral failure. The underlying mechanism is a cytokinergic storm, an emerging facet of immunological dysregulation. This clinical trial is aimed to understand the mechanisms of this immunological dysregulation in order to identify therapeutic levers. The main objective is to understand the relationships between clinical severity, death or morbidity of resuscitation management, and immune status (i.e., immune pathways activated or not). Immune status will be investigated at many levels of organization (i.e., circulating leukocytes, cytokines and chemokines, transcripts). The secondary objectives are : - to understand what is responsible for clinical severity, viral load, or immune activation; - to highlight the consequences of immunological dysregulation on associated risks (i.e., immunosuppression leading to the emergence of infectious comorbidities) as well as the functioning of neurotransmission through metabolic pathway diversions. The impact of dysimmunity on these biological pathways will be assessed with a metabolomic analysis; - to understand the mechanisms of vulnerability related to the field. Moreover, while co-morbidities are likely to be a risk factor for severe disease progression, there are many situations in which they do not occur. Stress, with its neurovegetative and endocrinological dimensions, modulates the immune response. It is essential to know whether the stress response plays a role in immunological dysregulation. This analysis is a prerequisite for understanding the conditions of treatment with glucocorticoids. Angiotensin converting enzyme type 2 (ACE2) also plays a likely role in host viral infection. It is also thought to play an important role in the emergence of severe syndromes by affecting the quality of vascular response.

Investigators use clinical data from a large sample of COVID-19 disease patients to screen out biomarkers associated with disease severity. Then, a novel nomogram model will be established to predict covid-19 disease severity, which could provide important assistance and supplement for clinical work. In the case of extremely shortage of front-line medical resources, patients with potential severe diseases will be timely treated with the help of the novel nomogram model.

This original study will assess the impact of the coronavirus health crisis on the management of patients undergoing medical treatment for cancer, in particularly on the modification of the hospital organization. It will also provide a record of the progress of patients who will have been treated during the epidemic period and infected by the virus. We will also assess the psychological impact of the pandemic in patients but also in caregivers

The COVID-19 pathology is frequently associated with diabetes mellitus and metabolic syndrome. In the epidemic outbreak that exploded at the beginning of 2020 in the Lombardy Region, about two thirds of the patients who died from COVID-19 were affected by diabetes mellitus. COVID-19 occurs in 70% of cases with an inflammatory pathology of the airways that can be fed by a cytokine storm and result in severe respiratory failure (10% cases) and death (5%). The pathophysiological molecular mechanisms are currently not clearly defined. It is hypothesized that the transmembrane glycoprotein type II CD26, known for the enzyme activity Dipeptilpeptidase 4 of the extracellular domain, may play a main role in this condition. It is in fact considerably expressed at the level of parenchyma and pulmonary interstitium and carries out both systemic and paracrine enzymatic activity, modulating the function of various proinflammatory cytokines, growth factors and vasoactive peptides in the deep respiratory tract. Of particular interest is the fact that Dipeptilpeptidase 4 has been identified as a cellular receptor for S glycoprotein of MERS-COV. In the case of the SARS-COV 2 virus, the main receptor is the Angiotensin-Converting Enzyme 2 protein, but a possible interaction with Dipeptilpeptidase 4 also cannot be excluded. The selective blockade of Dipeptilpeptidase 4 could therefore favorably modulate the pulmonary inflammatory response in the subject affected by COVID-19. This protein is also known for the enzymatic degradation function of the native glucagon-like peptide 1, one of the main regulators of insulin secretion. This is why it is a molecular target in the treatment of diabetes (drugs that selectively inhibit Dipeptilpeptidase 4 are marketed with an indication for the treatment of type 2 diabetes). It is believed that the use of a Dipeptilpeptidase 4 inhibitor in people with diabetes and hospitalized for Covid-19 may be safe and of particular interest for an evaluation of the effects on laboratory and instrumental indicators of inflammatory lung disease. Among the drugs that selectively block Dipeptilpeptidase 4, the one with the greatest affinity is Sitagliptin.

Several treatments have been used in during the Covid-19 pandemic of 2020. Using patients' registries from several hospitals in Paris, the investigators retrospectively analyzed associations between specific treatments, including but not limited to vaccines targeted against SARS-CoV-2, hydroxychloroquine, azithromycin, remdesivir, baricitinib, tocilizumab, sarilumab, lopinavir/ritonavir and oseltamivir; and clinical outcomes including, death and mechanical ventilation.

The outbreak of the 2019 Coronavirus (COVID-19) pandemic is a major stressor leading to increased levels of anxiety, and specifically, an excessive fear of being infected and affected by the disease among major parts of the population. At the same time, the access to mental health services is limited due to the lockdown policy applied in many countries worldwide, warranting the development of home-delivered interventions aimed at reducing stress and anxiety symptoms. Attention Bias modification (ABM) has been found to be an efficacious computerized intervention to reduce anxiety symptoms. In this open pilot trial, participants reporting on elevated levels of health anxiety concerning the COVID-19 epidemic will receive one session of ABM over 5 consecutive days (5 sessions total). Symptoms of health anxiety, state anxiety, generalized anxiety, and depression will be measured at baseline and post-treatment.

The safety and efficacy of a laryngoscopy as a primary intubation tool in urgent endotracheal intubation of cardiac arrest patients with suspected/confirmed COVID-19 has not been well-described in the literature. This study will answer whether using a Vie Scope laryngoscope will impact on the efficacy and safety of intubation compared with a traditional direct laryngoscopy.