COVID-19 Clinical Trials and Expanded Access

Experience from the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak taught thathealthcare workers (HCWs) often experience chronic stress effects for months or yearsafter such an event, and that supporting HCWs requires attention to the marathon ofoccupational stress, not just the sprint of dramatic stressors that occur whileinfections are dominating the news. This study will test if the well-being of hospitalworkers facing a novel coronavirus outbreak is improved by adding either of twointerventions: (1) Peer Resilience Champions (PRC): an interdisciplinary team ofprofessionals who actively monitor for early signs of heightened stress within clinicalteams, liaise between staff and senior management to improve organizationalresponsiveness, and provide direct support and teaching (under the supervision of expertsin resilience, infection control, and professional education). Investigators will testthe effectiveness of this PRC Intervention by rolling it out to different parts of thehospital in stages and comparing levels of burnout before and after the interventionreaches particular teams and units (a stepped wedge design). By the end of the study, PRCSupport will have been provided to all clinical and research staff and many learners (>6,000 people). Note that the provision of PRC support will be directed to the entireorganization. The research portion of the study is the evaluation of PRC support througha repeated survey completed by consenting staff. Investigators will test theeffectiveness of the PRC by measuring trends in burnout and other effects of stress overthe course of the study in a subgroup of hospital workers (as many as consent, target~1000 people) through an online questionnaire (called "How Are You?"). (2) The secondintervention is an enriched version of the "How Are You?" Survey, which providespersonalized feedback about coping, interpersonal interactions and moral distress.Participants will be randomized (1:1) to receive the shorter Express Survey (identifyingdata and outcome measures only), or the Enriched survey (all of the Express measures plusadditional measures with feedback based on responses). It is hypothesized that both thePRC intervention and the Enriched Survey intervention will help prevent or reduceinstances of burnout in HCWs.

The COVID-19 disease has been subject to numerous publications since its emergence.Almost 20% of people suffering from COVID-19 develop severe to critical symptoms andrequire hospitalization, often in Intensive Care Unit (ICU). Respiratory failure is themain reason for admission in ICU of these patients. Therapeutic strategies implementedfor the management of critically-ill patients may often lead to short-term muscular andfunctional alterations resulting in ICU-Acquired Weakness (ICUAW). These lead tolong-term disabilities expressing trough dependence and quality of life impairment ofsurvivors.The purpose of this study is to assess the quality of life, dependence and survival atone year in patients who survived from COVID-19 in ICU and are admitted in post-ICUsetting for difficult weaning purpose.Ancillary studies aim to assess the course of muscle function (atrophy, structuralmodifications), lung function (loss of aeration) and safety of early mobilization.

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.

In the last 10 years, severe acute respiratory infection (SARI) was responsible ofmultiple outbreaks putting a strain on the public health worldwide. Indeed, SARI had arelevant role in the development of pandemic and epidemic with terrible consequences suchas the 2009 H1N1 pandemic which led to more than 200.000 respiratory deaths globally.In late December 2019, in Wuhan, Hubei, China, a new respiratory syndrome emerged withclinical signs of viral pneumonia and person-to-person transmission. Tests showed theappearance of a novel coronavirus, namely the 2019 novel coronavirus (COVID-19). Twoother strains, the severe acute respiratory syndrome coronavirus (SARS-CoV) and MiddleEast respiratory syndrome coronavirus (MERS-CoV) have caused severe respiratoryillnesses, sometimes fatal. In particular, the mortality rate associated with SARS-CoVand MERS-CoV, was of 10% and 37% respectively.Even though COVID-19 appeared from the first time in China, quickly it spread worldwideand cases have been described in other countries such as Thailand, Japan, South Korea,Germany, Italy, France, Iran, USA and many other countries. An early paper reported 41patients with laboratory-confirmed COVID-19 infection in Wuhan. The median age of thepatients was 49 years and mostly men (73%). Among those, 32% were admitted to the ICUbecause of the severe hypoxemia. The most associated comorbidities were diabetes (20%),hypertension (15%), and cardiovascular diseases (15%). On admission, 98% of the patientshad bilateral multiple lobular and sub-segmental areas of consolidation. Importantly,acute respiratory distress syndrome (ARDS) developed in 29% of the patients, while acutecardiac injury in 12%, and secondary infection in 10%. Invasive mechanical ventilationwas required in 10% of those patients, and two of these patients (5%) had refractoryhypoxemia and received extracorporeal membrane oxygenation (ECMO). In a laterretrospective report by Wang and collaborators, clinical characteristics of 138 patientswith COVID-19 infection were described. ICU admission was required in 26.1% of thepatients for acute respiratory distress syndrome (61.1%), arrhythmia (44.4%), and shock(30.6%). ECMO support was needed in 11% of the patients admitted to the ICU. During theperiod of follow-up, overall mortality was 4.3%.The use of ECMO in COVID-19 infection is increasing due to the high transmission rate ofthe infection and the respiratory-related mortality.Therefore, the investigators believe that ECMO in case of severe interstitial pneumoniacaused by COVID could represent a valid solution in order to avoid lung injuries relatedto prolonged treatment with non-invasive and invasive mechanical ventilation. Inaddition, ECMO could have a role for the systemic complications such as septic andcardiogenic shock as well myocarditis scenarios. Potential clinical effects and outcomesof the ECMO support in the novel coronavirus pandemic will be recorded and analyzed inour project.The researchers hypothesize that a significant percentage of patients with COVID-19infection will require the utilize of ECMO for refactory hypoxemia, cardiogenic shock orseptic shock. This study seeks to prove this hypothesis by conducting an observationalretrospective/prospective study of patients in the ICU who underwent ECMO support anddescribe clinical features, severity of pulmonary dysfunction and risk factors ofCOVID-patients who need ECMO support, the incidence of ECMO use, ECMO technicalcharacteristics, duration of ECMO, complications and outcomes of COVID-patients requiringECMO support.

Multicenter investigation featuring an open-label lead-in followed by a double blinded,randomized, placebo-controlled Phase 2/3 part to evaluate the safety and efficacy ofMultiStem therapy in subjects with moderate to severe Acute Respiratory Distress Syndrome(ARDS) due to pathogens including COVID-19.

The project aims to clarify how immunity to SARS-CoV2 develops in humans and toinvestigate the possibility of finding patients with a particularly effective,neutralizing antibody response for future treatment. The project also aims to detail thevirus's damage mechanisms in tissue.