COVID-19 Clinical Trials and Expanded Access

Background: The human disease caused by SARS-CoV-2 is called COVID-19. In most cases, COVID-19 is a mild to moderate respiratory illness. But it can also be more severe and even lead to death. There is no vaccine to prevent SARS-CoV-2 infection. There is also no therapy to treat COVID-19. Researchers want to collect plasma from adults who have recovered from COVID-19, which may help them develop treatments. Objective: To collect anti-SARS-CoV-2 immune plasma from adult volunteers who have recovered from COVID-19. Eligibility: Males and females ages 18 to 70 who have a history of COVID-19 like illness or positive test for SARS-CoV-2, and have a minimum level of SARS-CoV-2 antibodies as specified by the study. Design: This study consists of 2 parts: 1) screening for SARS-CoV-2 antibody titer and eligibility to donate plasma and 2) plasma collection by apheresis. Study sites may participate in 1 part alone (either screening or plasma collection only) or both parts (screening and plasma collection). For screening part: Participants will be screened for their eligibility to join this research study with a medical history and physical exam. Their vital signs (blood pressure, heart rate, temperature, respiration rate) will be taken. Their weight and height will be recorded. They will give a blood sample for clinical laboratory tests of their general health and a research test for SARS-CoV-2 antibodies. They will discuss their history of COVID-19-like illness and any testing for SARS-CoV-2. They will be evaluated for their ability to donate plasma. For plasma collection part: Subjects meeting criteria for plasma donation and found to have high neutralizing antibody titers and who plan to donate plasma under this part of the study will be scheduled for 1 (and up to 20) plasma collection sessions. These will occur no less than 7 days apart. Prior to each donation, participants will have a brief physical exam and complete a donor history questionnaire. They will be asked about any current SARS-CoV-2 infection symptoms. At each donation, plasma will be taken through a standard apheresis procedure. For this, blood will be withdrawn through a needle placed in the participant's arm vein. A machine will separate the plasma from the red cells. The red cells will be returned to the participant, either through the same needle or through a second needle in the other arm. Participation may last up to 240 days.

The Investigators propose to set up a preventive trial of infection in hospital workers at risk of coronavirus infection by comparing the rate of SARS-Cov-2 infection in a population of negative SARS-Cov-2 hospital workers receiving preventively azithromycin, hydroxychloroquine or a Placebo

COVID 19 treatment using Remedesvir.

Vitamin D is a secosteroid hormone produced by the skin during Summer exposure to UVB rays. Hypovitaminosis D is common in Winter (October to March) at Northern latitudes above 20 degrees North, and from April to September at Southern latitudes beyond 20 degrees below the equator. In the past, coronaviruses and influenza viruses have exhibited very high seasonality, with outbreaks occurring preferentially during the Winter. The Covid-19 pandemic is indeed more severe above Winter latitudes of 20 degrees, while it remains until now less severe in the Southern hemisphere, with a much lower number of deaths. Preclinical research suggests that the SARS-Cov-2 virus enters cells via the angiotensin converting enzyme 2 (ACE2). Coronavirus viral replication downregulates ACE2, thereby dysregulating the renin-angiotensin system (RAS) and leading to a cytokine storm in the host, causing acute respiratory distress syndrome (ARDS). Research also shows that vitamin D plays a role in balancing RAS and in reducing lung damage. On the contrary, chronic hypovitaminosis D induces pulmonary fibrosis through activation of RAS. Similarly, hypovitaminosis D has been strongly associated in the literature with ARDS, as well as with a pejorative vital prognosis in resuscitation but also in geriatric units, and with various comorbidities associated to deaths during SARS-Cov-2 infections. Conversely, vitamin D supplementation has been reported to increase immunity and to reduce inflammatory responses and the risk of acute respiratory tract infections. High-dose oral vitamin D3 supplementation has been shown to decrease short-term mortality in resuscitation patients with severe hypovitaminosis D (17% absolute risk reduction). It is considered safe to take oral vitamin D supplementation at doses up to 10,000 IU/day for short periods, particularly in older adults, i.e. a population that is mostly affected by hypovitaminosis D and who should receive at least 1,500 IU of vitamin D daily to ensure satisfactory vitamin D status. Vitamin D supplementation is mentioned as a potentially interesting treatment for SARS-Cov-2 infection but on a scientific basis with a low level of evidence until now. We hypothesize that high-dose vitamin D supplementation improves the prognosis of older patients diagnosed with COVID-19 compared to a standard dose of vitamin D.

***At this time, we are only enrolling at Houston Methodist Hospital (HMH)/Baylor College of Medicine (BCM) and are not shipping cells outside of BCM/HMH.*** This is a study for patients who have respiratory infection caused by SARS-CoV-2 that have not gotten better. Because there is no standard treatment for this infection, patients are being asked to volunteer for a gene transfer research study using mesenchymal stem cells (MSCs). Stem cells are cells that do not yet have a specific function in the body. Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown from bone marrow (the spongy tissue inside of bones). Stem cells can develop into other types of more mature (specific) cells, such as blood and muscle cells. The purpose of this study is to see if MSCs versus controls can help to treat respiratory infections caused by SARS-CoV-2.

The study proposes to conduct an open-label Phase II trial to evaluate the feasibility, safety and early efficacy of hydroxychloroquine (HCQ) administration in reduction of transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and development of Corona Virus Disease 2019 (COVID-19) in high-risk, healthy acute care provider participants exposed, directly or indirectly, to COVID-19 patients. There is a more than 50 years track record of safety of HCQ for treatment and prevention of various disease states. Early data on use of HCQ for COVID treatment suggests anti-viral activity and immunomodulatory properties for reducing inflammation associated with COVID-19.

Evaluation of the efficacy and safety of Danoprevir sodium tablet combined with ritonavir for SARS-CoV-2 infected patients.

A total of 278 patients are planned. All patients will be in an early-stage of COVID-19. They must be adults and hospitalized. In this study, all participating patients will receive the standard treatment provided according to the current treatment protocols for coronavirus disease. In addition to this treatment, each patient will be randomly assigned to receive additional treatment with convalescent plasma transfusion (CP; blood plasma from patients who have been cured of coronavirus), or continue with standard treatment but without adding transfusion. 50% of the chances of additional treatment with CP, and 50% of the chances of receiving only the standard treatment for coronavirus. The duration of the study shall be one month from the assignment of the treatment. The patient and the doctor will know the treatment assigned.

This is a multi-centre study on lung cancer patients which experienced COVID-19. Information on clinical features, clinical course, management and outcomes will be collected for both, thoracic cancers and COVID-19 infection. Firstly, investigators will be registered in an online secure registry. After that, a protocol will be developed in order to collect clinical data for the research. It will also include I on the care organization or the perception of the patient and their family members. The final stage will consist on retrospective data collection from patients. So, it is a retrospective study data collection, preceded by prospective data registry.

Prone positioning is a well studied and validated treatment for severe acute respiratory distress syndrome (ARDS), however there are no randomized studies on the use of prone positioning in the non-intubated patient. It is unknown if this intervention would be helpful in preventing further respiratory deterioration in terms of increasing supplemental oxygen requirements, endotracheal intubation, and ICU admission. The Awake Prone Position for Early hypoxemia in COVID-19 (APPEX-19) Study is a pragmatic adaptive randomized controlled unblinded trial. APPEX-19 randomizes non-ICU patients with COVID-19 or who are under evaluation for COVID-19 to lie in a prone position (i.e, with their stomach and chest facing down) or to usual care.