COVID-19 Clinical Trials and Expanded Access

The recent and unexpected occurrence of patients with the development of skin lesions onthe hands and/ or feet has been described recently. As these cases occurredcontemporaneously with the Coronavirus Disease 2019 (COVID-19) and as it was the mostoften occurrence of de novo frostbites, the question raised of whether there is a directlink between the occurrence of these lesions and infection of the severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) the responsible for CoVID-19. Indeed,mechanisms of these lesions and the precise correlation with Sars-CoV-2 remains poorlyunderstood. Therefore, this study aim to: 1. Determine the possible link with this virus, 2. Understand the mechanisms involved in the pathogenesis of these lesions.

Detection of the incidence and types of arrhythmia and conduction block in COVID - 19patients Detection and description of CMR patterns of myocardial injury in COVID-19patients with arrhythmias.

The investigators are enrolling 100 healthcare Provider volunteers (n=100) from acrossthe United States to help to evaluate and document the financial impact of COVID-19 onPhysicians and other healthcare Providers. This investigation will compare individualPhysician revenues before and after the advent of the COVID-19 pandemic. Theinvestigators expect to be able to differentiate between revenues lost due to theCOVID-19-driven business recession and revenues lost due to the manipulation ofreimbursement processes by insurance companies. The inextricable linkage between Payerand Physician revenues suggests that Payer revenues are higher at the direct expense ofPhysicians, since both streams come from the same sources of funding. The secondaryobjective is aimed at revealing the methods Payers use to retain more money.

The outbreak of coronavirus disease 2019 (COVID-19), caused by infection of SARS-CoV-2,has rapidly spread to become a worldwide pandemic. Global research focused on theunderstanding of the biochemical infective mechanism and on the discovery of a fast,sensitive and cheap diagnostic tool, able to discriminate the current and past SARS-CoV-2infections from a minimal invasive biofluid. The fast diagnosis of COVID-19 isfundamental in order to limit and isolate the positive cases, decreasing with a promptintervention the infection spreading.The aim of the project is to characterize and validate the salivary Raman fingerprint ofCOVID-19, understanding the principal biomolecules involved in the differences betweenthe three experimental groups: 1) healthy subjects, 2) COVID-19 patients and 3) subjectswith a past infection by COVID-19. The large amount of Raman data will be used to createa salivary Raman database, associating each data with the relative clinical datacollected.Starting from the preliminary results and protocols of the Laboratory of Nanomedicine andClinical Biophotonics (LABION) - IRCCS Fondazione Don Gnocchi Milano, the salivacollected from each experimental group will be analysed using Raman spectroscopy. All thedata will be processed for the baseline, shift and normalization in order to homogenizethe signals collected and creating in this way the Raman database. The average spectrumcalculated from each group will be characterized, identifying the principal families ofbiological molecules responsible for the spectral differences.EXPECTED RESULTS: Verify the possibility to use Raman spectroscopy on saliva samples forthe identification of subjects affected by COVID-19. The principal aim of the project isto create a classification model able to: discriminate COVID-19 current and pastinfection, identify the principal biological molecules altered in saliva during theinfection, predict the clinical course of newly diagnosed COVID-19 patients, translationand application of the classification model to a portable Raman for the test of a pointof care.

In December 2019, a cluster of pneumonia cases of unidentified cause emerged in Wuhan,wasidentified as the culprit of this disease currently being identified as "CoronavirusDisease 2019" (COVID-19) by World Health Organization.Coronavirus was found to not only target the patient's lungs but also multiple organs.Around 2-33% of Coronavirus Disease-19 patients developed gastrointestinal symptoms.Studies have shown that Severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) wasfound in patient's feces, suggesting that the virus can spread through feces. In ourprevious study, stool samples from 15 patients with COVID-19 were analysed. Depletedsymbionts and gut dysbiosis were noted even after patients were detected negative ofSARS-CoV-2. A series of microbiota were correlated inversely with the disease severityand virus load. Gut microbiota could play a role in modulating host immune response andpotentially influence disease severity and outcomes.The investigators are uncertain about the impact of synbiotic on patients with COVID-19.However, a therapeutic strategy aiming at investigating the gut Imicrobiota of patientswith COVID-9 who take synbiotic or not, leading to lesser progression to severe disease,less hospital stay and improved quality of life.

Since the beginning of the year, the entire world has been concerned with the novelSARS-CoV2 virus. After the first case descriptions in Wuhan, there has been a rapidincrease in the number of cases in Germany as well. In case of an illness with the virus,the affected patients can suffer from a slight infection of the upper respiratory tractup to severe lung failure and death. Interestingly, up to now, children are usually lessseverely affected than adults. However, the actual infection rates are probably similarto those of adults, even if the actual prevalence in children is difficult to quantify sofar. The extent of the disease in children has also been less researched to date than inadults, and the same applies to pregnant women and their newborns. In addition, intensiveresearch into possible therapeutic strategies and new vaccines is necessary. Here,however, the number of clinical studies in children is also far behind. In order to beable to understand the infection process and to protect the population with theirchildren, comprehensive testing is necessary. However, this poses great challenges forlocal health authorities. Scientific investigations are also costly, but are alreadybeing carried out by many institutes. So far, for example in the SeBlueCo study, a verylow prevalence of antibodies (1.3% of people) has been show. In children, however, boththe routes of infection and the way the immune system deals with the virus are probablydifferent than in adults. In this study the investigators now want to examine residualblood samples from pediatric patients of the pediatric and adolescent clinic in the timecourse after the beginning of the pandemic in order to better understand and monitor thedevelopment of antibody prevalence.

The Multi-arm trial of Inflammatory Signal Inhibitors for COVID-19 (MATIS) study is atwo-stage, open-label, randomised controlled trial assessing the efficacy of ruxolitinib(RUX) and fostamatinib (FOS) individually, compared to standard of care in the treatmentof COVID-19 pneumonia. The primary outcome is the proportion of hospitalised patientsprogressing from mild or moderate to severe COVID-19 pneumonia. Patients are treated for14 days and will receive follow-up assessment at 7, 14 and 28 days after the first studydose. Patients with mild or moderate COVID-19 pneumonia will be recruited. Initially,n=171 (57 per arm) patients will be recruited in Stage 1. Following interim analysis toassess the efficacy and safety of the treatments, approximately n=285 (95 per arm) willbe recruited during Stage 2.

The non-essential and non-urgent follow-up consultations of patients living with HIV werepostponed or transformed into "teleconsultation" or exchanges of e-mails betweenpractitioners and patients during COVID-19 epidemic. This change in care can have animpact on follow-up and access to treatment for PVVIH.

A Pilot Study of the Use of Oscillation and Lung Expansion (OLE) Therapy in PatientsHospitalized with COVID-19

Primary Objective:Primary population (former smokers cohort): - Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former smokers with moderate-to-severe COPDSecondary Objectives:Primary population (former smokers cohort): - Evaluate the efficacy of itepekimab compared with placebo on pulmonary function in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on occurrence of acute exacerbation of COPD (AECOPD) in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on severe AECOPD in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on corticosteroid-treated AECOPD in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on respiratory symptoms in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on Forced Expiratory Volume in 1 second (FEV1) slope in former smokers with moderate-to-severe COPD - Evaluate the efficacy of itepekimab compared with placebo on health-related quality of life (HRQoL) as assessed by St. George's Respiratory Questionnaire (SGRQ) in former smokers with moderate-to-severe COPD - Evaluate the safety and tolerability of itepekimab in former smokers with moderate-to-severe COPD - Evaluate the pharmacokinetic (PK) profile of itepekimab in former smokers with moderate-to-severe COPD - Evaluate immunogenicity to itepekimab in former smokers with moderate-to-severe COPDSecondary population (current smokers cohort) - Estimate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate or severe COPD exacerbations in current smokers with moderate-to-severe COPD - Estimate the efficacy of itepekimab compared with placebo on pulmonary function in current smokers with moderate-to-severe COPD - Estimate the safety and tolerability of itepekimab in current smokers with moderate-to-severe COPD - Estimate the PK profile of itepekimab in current smokers with moderate to severe COPD - Estimate immunogenicity to itepekimab in current smokers with moderate-to-severe COPD