COVID-19 Clinical Trials and Expanded Access

This is an open label, dose escalating safety study of the advanced therapyinvestigational medicinal product (ATIMP) KI-MSC-PL-205, where patients diagnosed withSARS-CoV-2-induced severe acute respiratory distress syndrome (ARDS), according to theBerlin Definition, and who are on respirator/ventilator (used synonymously in thisprotocol) support due to respiratory insufficiency with or without concomitantcirculatory problems, will be included and treated with a single dose of KI-MSC-PL-205.

The COVID-19 crisis began in China in December 2019 and was declared a pandemic by theWorld Health Organisation on March 11th 2020. The pandemic has changed the way thatclinicians interact with and treat patients overnight. Staff within the NHS will be underhigh levels of stress due to the increased needs and worse outcomes of work as they areshielding or self-isolating and may feel helpless and guilty. The psychological impact ofthe pandemic will be prolonged and varied. It is vital that Investigators increaseunderstanding as much as possible to support NHS staff.The aim of this survey is to examine the possible mental health burden on NHS staff as aresult of the COVID-19 pandemic and how these change as the pandemic progresses. Byunderstanding these effects, it will allow researchers to identify recommendations toallow support mechanisms to be put in place for NHS staff, to better manage this andfuture pandemics and similar crises.Investigators are aiming to sample several cohorts of NHS staff including a subset ofstaff who are shielding. Staff will be asked to complete a series of online surveys atmultiple timepoint: on study initiation, 1 month later and then 3 months after thepandemic has ceased in the UK. Additional timepoints may be added depending on the lengthand severity of the pandemic.The main outcomes will be tracking changes in mental health measurements at thepre-defined timepoints. This work will allow Investigators to produce recommendationsabout the increased mental health support that NHS staff will need. If a need isdemonstrated then an interventional research project will be designed and implemented.

Background:People who are recovering from COVID-19 may continue to have problems that affect theirdaily life. For instance, they might feel overly tired. Researchers want to learn ifexercise can help people recover after COVID-19 infection.Objective:To study if participation in a rehabilitation exercise program can help people recoveringfrom COVID-19.Eligibility:Adults ages 18-80 with a lab-confirmed SARS-CoV2 infection (the virus that causesCOVID-19), and are still having some symptoms.Design:Participants will have a medical history and physical exam. They will give blood andurine samples. They will have tests to measure heart and lung function. Their bloodvessels will be assessed.Participants will have a computed tomography scan of the body. They will have anultrasound of the muscles in their arms, legs, and chest.Participants will take a 6-minute walk test. They will take other balance and movementtests.Participants will walk on a treadmill while hooked up to a monitor. Then they will beinterviewed. It will be audio-recorded.Participants will complete surveys about their symptoms and daily activities.Participants will take a smell test. For this, they will identify different smells. Theywill also have memory, attention, and mental functioning tests.Participants will wear an activity monitor on their wrist 24 hours a day. They willexercise 3 times a week for 10 weeks by moving vigorously on a track or treadmill for 30minutes. They will attend education classes once a week for 10 weeks.Participants will be contacted by phone or email every 3 months for 1 year after theycomplete the exercise part of the study. They will wear an activity monitor for up to 2weeks.

Evaluation of the agreement between fingerstick samples, venous blood, serum and plasmasamples when using the LumiraDx SARS-CoV-2 Ab Test against the reference method, usingstandard qualitative comparison techniques.

Older adults and those with chronic underlying health conditions are the most susceptibleto COVID-19 and its complications. Although there has been a rapid response to studyingthe effects of COVID-19 in the acute stages, little is known about recovery over thelonger-term. Older adults who survive the diseases are at risk of developing persistentmobility limitations due to extensive bed rest during hospitalization. For older patientsand those with underlying frailty recovering from COVID-19, this could rapidly lead tosignificant physical deconditioning and rapid declines in mobility. Understanding thetrajectory of functional recovery of older hospitalised patients with COVID-19 in theshort- and long-term is critical to improving patient outcomes and informing health andrehabilitative interventions for survivors.

The Innovative Support for Patients with SARS COV-2 Infections Registry (INSPIRE) studyis a CDC-funded COVID-19 project to understand the long-term health outcomes in recentlytested adults, both negative and positive, who have suspected COVID symptoms at the timeof their test. Participants will complete short online surveys every 3 months for 18months, share information about their health using a secure web-based platform, and arecompensated for their time.

This Phase 2/3 study is a multi-portion design to confirm that the chosen formulation anddosing regimen of CoVLP has an acceptable immunogenicity and safety profile.The Phase 3 portion is an event-driven, randomized, observer blinded, placebo-controlleddesign that will evaluate the efficacy and safety of the CoVLP formulation compared toplacebo.Subjects will be followed for safety and immunogenicity for a period of 12 months afterthe last vaccination.

This phase I trial evaluates the side effects and best dose of GEO-CM04S1 (previouslydesignated as COH04S1), a synthetic modified vaccinia Ankara (MVA)-based SARS-CoV-2vaccine, for the prevention of COVID-19 infection. COVID-19 infection is caused by theSARS-CoV-2 virus. SARS-CoV-2 has demonstrated the capability to spread rapidly, leadingto significant impacts on healthcare systems and causing societal disruption. GEO-CM04S1was created by placing small pieces of SARS-CoV-2 DNA (the chemical form of genes) intosynthetic MVA, which may be able to induce immunity (the ability to recognize and fightagainst an infection) to SARS-CoV-2. The purpose of the Phase 1 study is to determine thesafety and the optimal dose of the GEO-CM04S1 vaccine.The Phase 2 study is designed as a multi-center, double-blind, randomized, parallel,study to evaluate the safety profile of 2 dose levels of GEO-CM04S1 as a single boostershot to assess the immune response measured by the fold-increase in antibody againstSARS-CoV-2 Spike protein at day 28 post-injection among healthy adult volunteers.

Through SARS-CoV-2 IgG testing of PCR positive and negative cases the study will followthe COVID-19 immune response by monitoring the SARS-CoV-2 IgG antibody levels over aperiod of two years. Further, risk factors will be identified by the use of thetest-negative design including population controls, allowing comparison of participantswith positive and negative tests, and with population controls (triangulation). Specialemphasis will be on high risk groups in general and on different occupational,environmental and socio-economic groups in particular. Finally, severity of illness,deaths and the use of health care during will be assessed using national register datafrom Telemark and Agder.

To evaluate pulmonary changes and the results of a cardiopulmonary rehabilitationprotocol (CPRP) in patients after SARS-VOC-2 infection. Clinical trial type study to beconducted between 2020 and 2024 involving clinical-functional cardiopulmonary imaging andblood transcriptome profile: before CPRP (T1), 2 months after CPRP (T2) and 1 year later(T3). Expected results: a) clinical, image and transcriptome changes; b)clinical-functional improvement after CPRP.