COVID-19 Clinical Trials and Expanded Access

SOLIDARITY Finland Long-COVID trial assesses the effects of remdesivir + standard of care(SoC) vs. only SoC on long-COVID symptoms and quality of life (QoL) using questionnairesat one and two years post-discharge.Objectives i) Long-COVID symptoms - To investigate the effect of remdesivir (vs. SoC) on the occurrence of symptoms that have been associated with the long-COVID syndrome. The questionnaires will take place 1 and 2 years after the hospital admission. - The symptom questionnaire - that will be completed by patients at one and two years - measures basic patient information (age, height, weight, smoking status, major comorbidity, and working status) and a wide variety of potential long-COVID-symptoms and their bother (1. Fatigue; 2. Attention deficits; 3. Memory problems; 4. Sleeping difficulties; 5. Depressive mood; 6. Anxiety; 7. Dizziness; 8. Headache; 9. Tinnitus; 10. Paresthesias; 11. Changes in taste/smell perceptions; 12. Postexertional malaise; 13. Palpitations; 14. Chest discomfort; 15. Nausea; 16. Skin rash; 17. Joint aches; 18. Muscle pains; 19. Continuous cough; 20. Respiratory tract mucous discharges) in remdesivir and usual care armsii) Quality of life - EQ-VAS: to compare patients' quality of life in remdesivir and usual care arms. - EQ-5D-5L questionnaire assesses the following domains: 1. Mobility; 2. Self-care; 3. Usual activities; 4. Pain and discomfort; 5. Anxiety and depression; 6. The VAS of subjective perception of overall health.Additionally (at 1 or 2 years; depending on future funding and ethical approvaldecisions; currently the study has ethical approval for long-COVID and quality of lifeassessments only): - The Finnish healthcare registries (Statistics Finland Mortality Database and the HILMO Care Register for Health Care) will be used to estimate long-term mortality and incidence of major comorbidity in remdesivir and usual care arms - Lung function will be assessed using spirometry and diffusing capacity, as well as the six-minute walk test (6 mwt) in remdesivir and usual care arms - Whole-genome genotyping will be performed for a genome-wide association study to investigate genetic correlates of long-COVID-19 -symptoms in remdesivir and usual care armsUPDATE 02.02.2022:Primary outcomes will comprise the following: 1. EQ-VAS 2. EQ-5D-5L, summary 3. Does the patient feel recovered from COVID-19-infection at one year or not? (question no. 10) 4. Fatigue (questionnaire, question no. 14) 5. Exertional dyspnea (question no. 12)

The main aim of the study is to estimate the potential efficacy of i.v. canrenone asadd-on therapy on maximal medical treatment versus maximal medical treatment alone intreating moderate-to-severe ARDS due to SARS-CoV-2.

This phase 2 trial studies the immune response to GEO-CM04S1 (previously designated asCOH04S1) compared to standard of care (SOC) mRNA SARS-COV-2 vaccine in patients withblood cancer who have received stem cell transplant or cellular therapy.GEO-CM04S1 belongs to a category called modified vaccinia Ankara (MVA) vaccines, createdfrom a new version of MVA, called synthetic MVA. GEO-CM04S1 works by inducing immunity(the ability to recognize and fight against an infection) to SARS-CoV-2. The immunesystem is stimulated to produce antibodies against SARS-CoV-2 that would block the virusfrom entering healthy cells. The immune system also grows new disease fighting T cellsthat can recognize and destroy infected cells. Giving GEO-CM04S1 after cellular therapymay work better in reducing the chances of contracting coronavirus disease 2019(COVID-19) or developing a severe form of COVID-19 disease in patients with blood cancercompared to SOC mRNA SARS-CoV-2 vaccine.

Little is currently known about the immediate and long-term effect of COVID-19 on lungventilation (delivery of air to the lungs) and lung perfusion (delivery of blood to thelungs). Some people who survive COVID-19 may have lung ventilation and/or perfusioninjury that persists following COVID-19 recovery. This lung injury may be related toinflammation in the lung, breathlessness, exercise limitation and reduced quality oflife. Therefore, towards the goal of understanding the effects of COVID-19 on lunghealth, the purpose of this study is to characterize and understand the clinicalrelevance of COVID-19 related lung ventilation and perfusion injury and associatedinflammatory status, ≤4 weeks and 6-months following COVID-19 recovery in an asthmaticand healthy population. To do this, an asthmatic and healthy population who have, andhave not, been previously diagnosed with COVID-19 will be studied.

Viral pandemics, such as HIV and SARS-Cov-V1, have shown that they can lead to acute and/ or delayed neurological complications. At the actual context of the pandemicCoronavirus disease 2019 (COVID-19), neurological manifestations seem to be confirmedsince in 85% of COVID-19 patients, present neurological symptoms, including anosmia,ageusia, periorbital pain, dizziness, fatigue, even moderate headache, moderate memoryand/or behavioral disorders.However, these neurological manifestations are not well studied and their radiologicalfeatures are not well described. It is therefore important to assess these potentialneurological complications in COVID-19 patients. To the investigator knowledge, there isno previous study in the literature describing spectral brain changes in COVID +patients. Thus, the goal of this work is to describe the radiological semiology using MRIand particularly Magnetic Resonance Spectroscopic (MRS) biomarkers in the evaluation ofacute and / or delayed brain damage in COVID + patients presenting a neurologicalmanifestations that are initially related to the cranial nerves damage.

Background: There are no proven therapies specific for pulmonary dysfunction in patientswith acute hypoxemic respiratory failure (AHRF) caused by infections (includingCovid-19). The full spectrum of AHRF ranges from mild respiratory tract illness to severepneumonia, acute respiratory distress syndrome (ARDS), multiorgan failure, and death. Theefficacy of corticosteroids in AHRF and ARDS caused by infections remains controversial.Methods: This is a multicenter, randomized, controlled, open-label clinical trial testingdexamethasone in mechanically ventilated adult patients with established AHRF (includingARDS) caused by confirmed pulmonary or systemic infections, admitted in a network ofSpanish ICUs. Eligible patients will be randomly assigned to receive dexamethasone:either 6 mg/d x 10 days or 20 mg/d x 5 days followed by 10 mg/d x 5 days. The primaryoutcome is 60-day mortality. The secondary outcome is the number of ventilator-free daysat 28 days. All analyses will be done according to the intention-to-treat principle.

The Geneva Canton organized the health crisis of the COVID-19 epidemic around the care ofCOVID patients at the University Hospital (HUG), by moving the care of non-COVID patientsto private hospitals of the canton. The COVID epidemic appears to have been associatedwith a decrease in consultations and care for non-COVID patients. An excess of morbidityand mortality (non-COVID) would be possible during or after the epidemic in connectionwith this "under-medicalization" of non-COVID patients.The aim of this study is to measure and analyze the impact on the morbidity and mortalityof inpatients during and after the COVID-19 epidemic in the adult inpatient wards of HUGand township hospitals / clinics.

This is an open-label, randomized, multi-centre study where hospitalized subjects will berandomized in a 2:1 ratio to receive Isoquercetin (IQC-950AN) in addition to standard ofcare or standard of care only for 28 days following confirmation of a COVID-19 infection.

Automated quantification of the pulmonary volume impaired during acute respiratoryfailure could be helpful to assess patient severity during COVID-19 infection orperioperative medicine, for example.This study aim at assessing the correlation between the amount of radiologic pulmonaryalteration and the clinical severity in two clinical situation : 1. SARS-CoV-2 infections 2. Postoperative hypoxemic acute respiratory failure

Novel coronavirus 2019 (COVID-19) has emerged as a major international public healthconcern. While much of the morbidity and mortality associated with COVID-19 has beenattributed to acute respiratory distress syndrome (ARDS) or end-organ failure, emergingdata suggest that disorders of coagulation, in particular hypercoagulability and venousthromboembolism (VTE), may represent an additional major, and possibly preventable,complication (Wu C, et al. JAMA Intern Med. 2020 Mar 13. [Epub ahead of print] and TangN, et al. Thromb. Haemost. 2020 Feb 19. [EPub Ahead of Print]). Abnormal coagulationtesting results, especially markedly elevated D-dimer and FDP, have been associated witha poor prognosis in COVID-19 infection. We propose the following Electronic Health Record(EHR)-guided 10000-patient, retrospective observational cohort study to assess VTEincidence, risk factors, prevention and management patterns, and thrombotic outcomes inpatients with COVID-19 infection. In order to gain the valuable perspective of otherregional and national centers providing care for large populations of COVID-19, we havestarted a collaborative network with 5 additional sites which will provide us withde-identified data from 1000 patients each. These 5000 patients in addition to the5000-patient cohort we are enrolling within the Mass General Brigham Network willcomprise this study population.