COVID-19 Clinical Trials and Expanded Access

The coronavirus disease 2019 (COVID-19) global pandemic caused by the severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable morbidity andmortality in over 170 countries. Increasing age and burden of cardiovascularcomorbidities are associated with a worse prognosis among patients with COVID-19. Inaddition, serologic markers of more severe disease including coagulation abnormalitiesand thrombocytopenia, are not uncommon among patients hospitalized with severe COVID-19infection and are more common in patients who died in-hospital. As the COVID-19 pandemiccontinues to grow, there is a pressing need to identify safe, effective, and widelyavailable therapies that can be scaled and rapidly incorporated into clinical practice.Understanding the putative mechanism of increased mortality risk associated with abnormalcoagulation function and cardiac injury is critical to guide studies of promisingtherapeutic interventions. Published and anecdotal reports indicate that endothelialdysfunction and thrombosis are common in critically ill patients with COVID-19, includingreports of diffuse microvascular thrombosis in the lungs, heart, liver, and kidneys.Patients with cardiovascular disease (CVD) and CVD risk factors are known to haveendothelial dysfunction and a heightened risk of thrombosis. A recent study of COVID-19inpatients from Wuhan, China observed that an elevated D-dimer level greater than 1 ug/mLwas associated with an 18 times higher risk of in-hospital death, underscoring theimportance of increased coagulation activity as a potential modifiable risk marker thatmay drive end-organ injury. Given the established link between endothelial dysfunctionand thrombosis in patients with cardiovascular disease, and the association betweencoagulopathy and adverse outcomes in patients with sepsis, the association betweenincreased coagulation activity, end-organ injury, and mortality risk may represent amodifiable risk factor among COVID-19 patients with critical illness. Therefore, wepropose to conduct a randomized, open-label trial of therapeutic anticoagulation inCOVID-19 patients with an elevated D-dimer to evaluate the efficacy and safety.

This retrospective study aims to perform a medication risk stratification using drugclaims data and to simulate the impact of the addition of various repurposed drugs on theMedication Risk Score (MRS) in a health insurance population. Our clinical tool wouldenable us to identify potential multi-drug interactions and potentially reduce the riskof adverse drug events (ADE) developing in these patients infected with COVID-19.

Prospective study evaluating the outcomes of implementation of a protective protocol forCovid-19 for patients and staff in a large endoscopy unit.

The primary objective of the study is to evaluate cardiac and pulmonary hemodynamicchanges over time as predictor of disease progression and outcome in COVID-19 patientsadmitted to ICU.The primary endpoint is the occurrence of a major event predefined as either: death(all-cause mortality) or discharge from ICU (limit of 4 months).This is a uni-center prospective observational cohort study with an inclusion period of 2months. The end of the study is foreseen in 6 months.

Patient are being asked to provide respiratory and blood samples for a clinical researchstudy because the patients have a virus called the novel coronavirus, or SARS-CoV-2, thatcauses the disease known as Covid-19.Investigators do not know a lot about this virus, including all the ways it travels fromperson to person. Investigators also do not know if a person will get sick or not fromthe virus after being in close contact with someone who has the virus. Because of this,investigators are performing research on the virus found in respiratory secretions to getmore information on how investigators can best detect and treat this new virus in thefuture.Primary Objective - To determine the clinical characteristics and outcomes of Covid-19 in children. - To characterize the clinical risk factors of Covid-19 in children..Secondary Objectives - To characterize the immunological risk factors and serologic response to SARS-CoV-2 infection in children.- To evaluate the duration of viral shedding in children. - To evaluate the duration of SARS-CoV-2 viral shedding in children. Exploratory Objective

The COVID-19 outbreak has been rapidly transmitted in late January 2020 and arousedenormous attention globally. The public at large may also experience boredom,disappointment, and irritability under the isolation measures. Depression and anxiety arecommon mental health problems experienced by university students. This survey aims toinvestigate the psychological impact of COVID 19 on students.

Patients with COVID-19 diagnoses are treated under isolation in hospitals and withhigh-stress level. Currently, there is little information on the mental healthimplications of exposure amongst COVID-19 survivors and their family members. Researchexploring the psychological impact amongst survivors of exposure to COVID-19 isdesperately needed to understand the effects, mental health toll, and support required insurvivors of COVID-19. This study aims to assess the psychological impact of the COVID-19outbreak on COVID-19 survivors and their family members.

The COVID-19 pathology is frequently associated with diabetes mellitus and metabolicsyndrome. In the epidemic outbreak that exploded at the beginning of 2020 in the LombardyRegion, about two thirds of the patients who died from COVID-19 were affected by diabetesmellitus. COVID-19 occurs in 70% of cases with an inflammatory pathology of the airwaysthat 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 clearlydefined. It is hypothesized that the transmembrane glycoprotein type II CD26, known forthe enzyme activity Dipeptilpeptidase 4 of the extracellular domain, may play a main rolein this condition. It is in fact considerably expressed at the level of parenchyma andpulmonary interstitium and carries out both systemic and paracrine enzymatic activity,modulating the function of various proinflammatory cytokines, growth factors andvasoactive peptides in the deep respiratory tract. Of particular interest is the factthat Dipeptilpeptidase 4 has been identified as a cellular receptor for S glycoprotein ofMERS-COV. In the case of the SARS-COV 2 virus, the main receptor is theAngiotensin-Converting Enzyme 2 protein, but a possible interaction withDipeptilpeptidase 4 also cannot be excluded. The selective blockade of Dipeptilpeptidase4 could therefore favorably modulate the pulmonary inflammatory response in the subjectaffected by COVID-19. This protein is also known for the enzymatic degradation functionof 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 selectivelyinhibit Dipeptilpeptidase 4 are marketed with an indication for the treatment of type 2diabetes). It is believed that the use of a Dipeptilpeptidase 4 inhibitor in people withdiabetes and hospitalized for Covid-19 may be safe and of particular interest for anevaluation of the effects on laboratory and instrumental indicators of inflammatory lungdisease. Among the drugs that selectively block Dipeptilpeptidase 4, the one with thegreatest affinity is Sitagliptin.

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

The unexpected onset of SARS-COV2 infection modified our practices, especially in routinemedicine. In order to reverse the epidemic curve of severe cases and slow the spread ofthe infection, confinement was generalized in France from March 13, 2020.Theserestrictive measures were imposed on anyone with symptoms compatible with the infection,with the exception of dyspnea and other criteria of severity. March 12, 2020 is thepivotal date when the management of COVID came to interfere with medical and healthcareorganizations. From this date, it is likely that some imaging or endoscopic exams havebeen de-scheduled for symptoms that are sometimes wrongly judged to be non-urgent andhave seen their numbers drop dramatically.Otherwise, concerning lung cancer, preventivemeasures have been extremely strengthened. For instance, it is recommended to delaysurgeries for localized tumors, to relieve or remove some chemotherapy or to deleteradiotherapy sessions deemed non-essential. However, symptoms that may initially beattributed to viral infection, such as cough, fever, fatigue, or chest pain may beclinical indicators of early-stage Lung cancer. In addition, lung cancer is likely tomake the patient more susceptible to pneumopathy, due to a weakened of immune response toviruses and bacteria. Consequently, as necessary as the restriction measures are, a riskof slowing down in the management of the Lung cancer pathology exists.The CBP-COVID Study intends to assess consequences of restrictive measures linked to theSARS-COV2 epidemic, by comparing clinical characteristics at diagnosis, treatment timesand treatments, regarding to 2 distinct time periods identical to the calendar, but onein 2019, the other in 2020.