COVID-19 Clinical Trials and Expanded Access

Study into the effects of daily use of metformin and low-dose naltrexone (LDN) for 4 weeks to reduce symptoms, disease severity, and recovery time from COVID-19.

The clinical syndrome associated with infection of the Coronavirus Disease 2019 (COVID-19) is notable for its variable clinical expression. Infection and transmission of the virus by asymptomatic individuals have been noted and represent one end of the clinical spectrum, while multi-organ failure, particularly pulmonary failure, and death represent the most severe end of the clinical spectrum. In a recent study published from the investigator's institution about the first 393 patients with COVID-19, 77.1% had a fever, a mechanism driven by IL-1. This suggests that there may be an excess release of IL-1 present. Cytokine storm syndrome (CSS) has been observed in patients with COVID-19 and has been proposed to contribute to the acute pulmonary failure that occurs. In distinct clinical settings, macrophage activation syndrome, elevated levels of pro-inflammatory cytokines, including IL-1, IL-6, and others, as well as elevations in laboratory indicators, including ferritin, CRP, d-dimer, and lymphopenia, have been observed. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Anakinra, a recombinant IL-1 receptor antagonist, has shown promise in treating CSS. It inhibits both IL-1-alpha and IL-1-beta. It is an FDA approved medication used in rheumatoid arthritis (RA) and Cryopyrin-Associated Periodic Syndromes (CAPS). Anakinra's ability to inhibit both IL-1 subtypes and short half-life makes it favorable to some experts. In the investigator's case-series, using anakinra in patients with COVID-19 showed promising in preventing the need for mechanical ventilation, and mortality subsequently. This study will determine the efficacy of anakinra, an interleukin (IL) -1 receptor blocker, in reducing the need for mechanical ventilation and/or 28-day mortality among patients with COVID-19 who have features of CSS and severe respiratory failure. The investigators will test the hypothesis that the proportion of subjects with COVID-19, features of CSS, and severe respiratory failure (World Health Organization (WHO) category 4 or 5) alive and without having required mechanical ventilation at day 28 from randomization will be 18% higher among those that receive anakinra compared to those that receive a placebo. A secondary hypothesis is that the number of subjects alive at 60-days will be higher amongst those who receive anakinra compared to those who receive a placebo.

In this 30-month study, the investigators propose to develop a culturally appropriate vaccine confidence intervention, targeting positive change related to HPV vaccine uptake behavior and reducing sentiments of hesitancy towards a COVID-19 vaccine, that can be seamlessly integrated into the existing environment of pediatric and family practice clinics in rural Alabama. To do so, the investigators will first assess stakeholders' knowledge, sentiments, and beliefs related to vaccination in general, a COVID-19 vaccination, and the HPV vaccination. The investigators will also assess stakeholders' perceptions of barriers to vaccination that exist in rural Alabama. This will occur in Aim 1. Then, in Aim 2, the investigators will use these data to inform the development of a non-invasive, modular synchronous counseling intervention targeting 15-17 year old adolescents (rationale for this age range presented later in this proposal). After the intervention has been finalized, in our final aim, Aim 3, we will conduct a hybrid type 1 effectiveness-implementation cluster randomized control trial to assess intervention acceptability and feasibility (N=4 clinics; N=120 adolescents), while also assessing for a "clinical signal" of effectiveness. To support dissemination and scale up, also during Aim 3, we will document implementation contexts to provide real-world insight. To do this, the investigators will conduct in-depth interviews with the same groups of stakeholders that we interviewed in Aim 1.

Background: In early 2020, many people thought Cambodia would have a serious COVID-19 outbreak due to the high number of Chinese travelers going to Cambodia. But as of June 14, 2020, only 128 cases of COVID-19 have been identified in the country. Many of these cases have been from people who had traveled in Europe. Researchers want to do antibody tests on blood from a sampling of people in Phnom Penh to learn the infection risks for people in the greater Phnom Penh area. Objective: To estimate the level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the blood of people living in Phnom Penh, Cambodia. Eligibility: Healthy males and females age 18-65 living in Phnom Penh since January 2020. Design: A mobile unit will travel to schools, shopping areas, parks, and pagodas around Phnom Penh. Participants will be screened with questions about their age and where they live. They will have blood taken via fingerstick. About 80 uL of blood will be taken. It will be tested for SARS-CoV-2. This visit will take about 30 minutes. If the test result is positive, participants will be contacted by phone. They will be asked to have a second blood draw. This time, 20 mL of blood will be taken. They can have this visit at their home or in a clinic. This visit will take about 30 minutes. If a participant has an adverse event, the mobile units and at-home units will have the tools needed to aid the participant. If needed, the participant will be sent to a nearby clinic.

Coronavirus Disease 2019 (COVID-19) (previously called 2019-nCOV acute respiratory disease) is caused by SARS-CoV-2, a positive-sense single-stranded RNA virus of the coronavirus family. The coronaviruses are largely responsible for the common cold, the 2002 SARS outbreak in Guangdong, China, the 2012 MERS outbreak in Saudi Arabia, and the present COVID-19 outbreak that originated in Wuhan, China. Much has been reported by way of systemic injury caused by COVID-19 affecting the cardiovascular, hepatic, nervous systems. These conditions are likely the result of the virus overwhelming the immune system. For these reasons, the investigators wish to conduct this study using existing medications off-label, and over-the-counter supplements to support the immune response, prevent lasting injury, and hasten the recovery from COVID-19.

This is a randomized, placebo-controlled study to assess the safety, PK profile, and efficacy of COVI-AMG in subjects with COVID-19.

The human immune system is enhanced by exposure to infrared radiation with the wavelength of 5 microns to 20 microns. Humans, at normal body temperature, radiate most strongly in the infrared at a wavelength of about 10 microns. Infrared energy sustains life and can be used to treat and prevent diseases, including Covid-19 infections. High temperature within the fever range obtained from infrared radiation causes the killer T-Cells to profilate. The Killer T-Cells improves ones immune system. The high temperature kills the Corona virus. In addition, multi-vitamins and minerals including high doses of Vitamin C, increase one's immune system. Vitamin C is an anti-oxidant, produces hydrogen peroxide and removes free radicals from the body. Pre-clinical trials conducted in Houston, Texas, using Vitality Therapy or the Bible Cure were successful in curing Covid-19 infections. It is therefore possible that Vitality Therapy or the Bible Cure can be used for the successful prevention and treatment of coronavirus infections.

Patients diagnosed with COVID-19 infection will be offered treatment with Opaganib, 500 mg Q12 hours. Opaganib will be continuously administered for up to 2 weeks, until discharged on room air (if earlier than 2 weeks).

The purpose of this study is to demonstrate the safety of Umbilical Cord Tissue Derived Mesenchymal Stem Cells (UCMSCs) administered intravenously in patients with acute pulmonary inflammation due to COVID-19 with moderately severe symptoms

To determine the efficacy of high dose Vitamin D (an over-the-counter nutritional supplement) in preventing immune-related complications in outpatients with confirmed SARS-CoV-2 infection.