COVID-19 Clinical Trials and Expanded Access

The COVID-19 disease has been subject to numerous publications since its emergence.Almost 20% of people suffering from COVID-19 develop severe to critical symptoms andrequire hospitalization, often in Intensive Care Unit (ICU). Respiratory failure is themain reason for admission in ICU of these patients. Therapeutic strategies implementedfor the management of critically-ill patients may often lead to short-term muscular andfunctional alterations resulting in ICU-Acquired Weakness (ICUAW). These lead tolong-term disabilities expressing trough dependence and quality of life impairment ofsurvivors.The purpose of this study is to assess the quality of life, dependence and survival atone year in patients who survived from COVID-19 in ICU and are admitted in post-ICUsetting for difficult weaning purpose.Ancillary studies aim to assess the course of muscle function (atrophy, structuralmodifications), lung function (loss of aeration) and safety of early mobilization.

SARS-CoV-2, has caused an international outbreak of respiratory illness termed Covid-19.The investigators used peptides derived from SARS-CoV-2 virus, to study viral-specificimmune responses. COV-CREM is a French prospective monocentric study that will evaluateviral-specific cell responses in positive patients for SARS-CoV-2 on the basis of(RT-PCR) assay performed in respiratory tract sample tested by our local Center forDisease Control.

The project aims to clarify how immunity to SARS-CoV2 develops in humans and toinvestigate the possibility of finding patients with a particularly effective,neutralizing antibody response for future treatment. The project also aims to detail thevirus's damage mechanisms in tissue.

Since December 2019, a new disease named COVID-19 linked to a new coronavirus, SARS-CoV2has emerged in China in the city of Wuhan, Hubei province, spreading very quickly to all5 continents, and responsible for a pandemic. France is the third most affected countryin Europe after Italy and Spain. Groups of patients at a higher risk of developing asevere form of COVID-19 have been defined: this include patients with immunosuppressivedisease as cancer or patients with advanced cirrhosis of the liver. Coronavirus liverinjury had been described with SARS-CoV 1 and MERS-CoV. There is no data on liver damageassociated with COVID-19 infection for compensated or decompensated cirrhotic patients.The objectives of this project are to estimate the incidence of COVID-19 inhepatocellular carcinoma population, both hospital and ambulatory, and to study theimpact on the frequency of severe forms, the prognosis, but also liver function, and themanagement of hepatocellular carcinoma, in this context of pandemic

The purpose of this data repository is to provide a secure and centralized storagelocation and resource for the collection of essential data and medical specimens, acrossCOVID-19 related protocols at Duke.

Some authors have proposed the use of the flu vaccine to reduce the severity of COVID-19cases, while some have proposed the use of ACE Inhibitors (ACEI) or Angiotensin Receptorblockers (ARB), since this virus shares hemagglutinin as a transmission mechanism andacts on the ACE2 enzyme during infection.Other authors described how none of the elderly patients receiving antihistamines andazythromycin in two nursing homes in Toledo -Spain- during the first wave died or neededhospital admission, even considering that 100% of residents had a positive serologicaltest after that wave. Other authors have described a positive evolution in patientsreceiving amantadine for their Parkinson's disease.The aim is to evaluate whether the admitted patients who are previously vaccinated orthose who were already receiving these treatments showed a better evolution.

The novel coronavirus (SARS-CoV-2) has spread all around the world and testing has poseda challenge globally. Health care providers are highly exposed and are an important groupto test. On top of these concerns, health care workers are also stressed by the needs onresponders in the COVID-19 crisis. The investigators will look at different ways tomeasure how common COVID-19 is among health care workers, how common is the presence ofantibodies by serological tests (also known as serostatus). The investigators willdescribe health worker mental and emotional well-being and their coping strategies intheir institutional settings. Lastly, the investigators will describe how knowingserostatus can affect individuals' mental and emotional well-being and how to cope in themidst of the COVID-19 response. This will help to how to better test and help healthcareworkers in the COVID-19 pandemic and prepare for possible future outbreaks.

The main objectives of this study are 1) to establish the prevalence of SARS-CoV-2 inasymptomatic healthcare workers (HCWs) in an early phase of community spread as well as2) to monitor the future spread of the disease by assessing serological responses toSARS-CoV-2 in symptomatic and asymptomatic HCWs over time and 3) to improve theassessment of the immune response and its protective effect as well as the assessment ofinfectivity of affected HCWs and 4) to evaluate the value and significance of antibodyformation and serological antibody tests and 5) to be able to evaluate possible futurepreventive and / or therapeutic approaches against SARS-CoV-2, e.g. to assess vaccinationeffects

The etiological agent of the current pandemic is a (+)ssRNA virus. SARS-CoV-2 isinfecting thousands of people in the world with a fatality rate that varies from 0.1 to5% in affected countries, thereby causing enormous economic losses. Few antibiotics haveshown any efficacy in their combat, but have not yet proven adequate to stop the spreadof the disease, nor are there any approved vaccines at the moment. From experiments inplants ongoing infections by RNA viruses, using thermotherapy, which is the applicationof heat at a temperature between 35-43 °C, the investigators know that raising thetemperature affects the transcription of viral proteins due to the formation of small RNAmolecules that interrupt the replication process by grouping in specific regions of theRNA molecule, preventing and inhibiting transcription. These small molecules are calledsmall interfering RNAs (siRNAs). This feature has been used through thermotherapy inhumans to combat the rapid replication of cells (i.e. cancer cells), attack cellsinfected by RNA viruses, and in the treatment of some parasitic infections.There arevarious commercially available devices for thermotherapy use in humans; they are mainlybeing used to ease muscle pain. They work by increasing the temperature in the rangerecommended for thermotherapy in humans 39-43 ° C. Therefore, the investigators considerthis treatment modality can be used to aid in the elimination of SARS-CoV-2 from thehuman body, decreasing viral load, which could allow the immune system time for itscontrol and elimination.

Background:People who get infected with COVID-19 have an unpredictable risk to worsen and die. Thismakes it hard to decide who can quarantine at home and who should be treated at ahospital. Researchers think the risk may be related to how a person s B and T cellsrespond to the virus. B and T cells are the major components of a person s immuneresponse. B and T cells responding to the virus with a favorable pattern may lead torecovery, and this favorable pattern may be helpful to establish. If people in a vaccinetrial get this same favorable pattern when responding to a vaccine, this may be a usefulearly signal that the vaccine will be successful.Objective:To examine how immune cells respond to COVID-19 infection.Eligibility:Adults ages 18 and older who have a confirmed or suspected COVID-19 infection or hadCOVID-19 in the past.Also, healthy donors with no suspected COVID-19 infectionDesign:Participants will be screened with medical record review.Participants will be tested with a research assay to determine who was infected withCOVID-19 and who was not. This test will be used to understand research results, not toadvise patients.Participants with active infection must be isolated, usually in a hospital.Other participants may give blood samples at NIH or at their local doctor s office orlab.Participants may give blood samples up to three times a week for a total of ten times,and may also give blood samples after starting a vaccine trial.Participants will be contacted by phone or email every 2 months for up to 2 years.