COVID-19 Clinical Trials and Expanded Access

This is a randomized, double-blinded, placebo-controlled study of AVM0703 administered asa single intravenous (IV) infusion to patients with moderate or severe immediatelylife-threatening Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 or influenza(A or B). The study is designed to evaluate the safety, tolerability, andpharmacokinetics of single dose of AVM0703 in these ARDS patients.

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 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 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.

Emergent experimental and anecdotal evidence has indicated that critically ill COVID-19patients demonstrate two patient sub-types (called phenotypes). In one group the diseaseprogresses slowly and patients have a low potential of developing mild respiratoryfailure, but in the other group, an exaggerated immune response(hyper-inflammation/cytokine storm) may be linked to the onset of precipitous respiratoryfailure, termed acute respiratory distress syndrome. This syndrome is responsible for alarge portion of COVID-19 associated mortality. Thus, determining links betweenhyper-inflammation and acute respiratory distress syndrome in COVID-19 patients is ofimmediate importance. Blood samples will undergo a number of analyses to help us tounderstand as much as possible about COVID-19. We will also study any differences inphysiologic and cytokine levels before and after patients are treated withimmunomodulatory therapies as part of clinical care in COVID-19 patients.

This study seeks to determine whether the virus which causes COVID-19, SARS-CoV-2, isshed in the stools of patients who are infected.

LIINC is a study of volunteers who were previously infected with SARS-CoV-2 (also knownas novel coronavirus or COVID-19) who have recovered from acute infection. The study isdesigned to provide a specimen bank of samples with carefully characterized clinicaldata. LIINC specimens will be used to examine multiple questions involving the virologic,immunologic, and host factors involved in COVID-19, with a focus on understandingvariability in the long-term immune response between individuals.

The aim of this study is to evaluate the safety and efficacy of autologousadipose-derived mesenchymal cells for treating confirmed or suspected patients withSARS-CoV-2 and compromised respiratory function requiring hospitalization.The hypothesis of the Study is autologous adipose-derived mesenchymal cells given IV toeligible patients will improve clinical outcomes of COVID 19 positive patients withsevere pneumonia or ARDS by reducing or avoiding cytokine storm.