COVID-19 Clinical Trials and Expanded Access

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.

In the last 10 years, severe acute respiratory infection (SARI) was responsible ofmultiple outbreaks putting a strain on the public health worldwide. Indeed, SARI had arelevant role in the development of pandemic and epidemic with terrible consequences suchas the 2009 H1N1 pandemic which led to more than 200.000 respiratory deaths globally.In late December 2019, in Wuhan, Hubei, China, a new respiratory syndrome emerged withclinical signs of viral pneumonia and person-to-person transmission. Tests showed theappearance of a novel coronavirus, namely the 2019 novel coronavirus (COVID-19). Twoother strains, the severe acute respiratory syndrome coronavirus (SARS-CoV) and MiddleEast respiratory syndrome coronavirus (MERS-CoV) have caused severe respiratoryillnesses, sometimes fatal. In particular, the mortality rate associated with SARS-CoVand MERS-CoV, was of 10% and 37% respectively.Even though COVID-19 appeared from the first time in China, quickly it spread worldwideand cases have been described in other countries such as Thailand, Japan, South Korea,Germany, Italy, France, Iran, USA and many other countries. An early paper reported 41patients with laboratory-confirmed COVID-19 infection in Wuhan. The median age of thepatients was 49 years and mostly men (73%). Among those, 32% were admitted to the ICUbecause of the severe hypoxemia. The most associated comorbidities were diabetes (20%),hypertension (15%), and cardiovascular diseases (15%). On admission, 98% of the patientshad bilateral multiple lobular and sub-segmental areas of consolidation. Importantly,acute respiratory distress syndrome (ARDS) developed in 29% of the patients, while acutecardiac injury in 12%, and secondary infection in 10%. Invasive mechanical ventilationwas required in 10% of those patients, and two of these patients (5%) had refractoryhypoxemia and received extracorporeal membrane oxygenation (ECMO). In a laterretrospective report by Wang and collaborators, clinical characteristics of 138 patientswith COVID-19 infection were described. ICU admission was required in 26.1% of thepatients for acute respiratory distress syndrome (61.1%), arrhythmia (44.4%), and shock(30.6%). ECMO support was needed in 11% of the patients admitted to the ICU. During theperiod of follow-up, overall mortality was 4.3%.The use of ECMO in COVID-19 infection is increasing due to the high transmission rate ofthe infection and the respiratory-related mortality.Therefore, the investigators believe that ECMO in case of severe interstitial pneumoniacaused by COVID could represent a valid solution in order to avoid lung injuries relatedto prolonged treatment with non-invasive and invasive mechanical ventilation. Inaddition, ECMO could have a role for the systemic complications such as septic andcardiogenic shock as well myocarditis scenarios. Potential clinical effects and outcomesof the ECMO support in the novel coronavirus pandemic will be recorded and analyzed inour project.The researchers hypothesize that a significant percentage of patients with COVID-19infection will require the utilize of ECMO for refactory hypoxemia, cardiogenic shock orseptic shock. This study seeks to prove this hypothesis by conducting an observationalretrospective/prospective study of patients in the ICU who underwent ECMO support anddescribe clinical features, severity of pulmonary dysfunction and risk factors ofCOVID-patients who need ECMO support, the incidence of ECMO use, ECMO technicalcharacteristics, duration of ECMO, complications and outcomes of COVID-patients requiringECMO support.

Multicenter investigation featuring an open-label lead-in followed by a double blinded,randomized, placebo-controlled Phase 2/3 part to evaluate the safety and efficacy ofMultiStem therapy in subjects with moderate to severe Acute Respiratory Distress Syndrome(ARDS) due to pathogens including COVID-19.

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.

Rationale In a very short time corona virus disease 2019 (COVID-19) has become a pandemicwith high morbidity and mortality. The main cause of death is respiratory failureincluding acute respiratory distress syndrome, however the exact mechanisms and otherunderlying pathology is currently not yet known. In the current setting of the COVID-19pandemic complete autopsies seem too risky due to the risk of SARS CoV-2 transmission.Yet, as so little is known, additional histopathological, microbiological and virologicstudy of tissue of deceased COVID-19 patients will provide important clinical andpathophysiological information. Minimal invasive autopsy combined with postmortem imagingseems therefore an optimal method combining safety on the one hand yet provingsignificant information on the other.This study aims to determine the cause of death and attributable conditions in deceasedCOVID-19 patients. This will be performed using post-mortem CT-scanning plus CT-guidedMIA to obtain tissue for further histological, microbiological and pathologicaldiagnostics. In addition, the pathophysiology of COVID-19 will be examined by furthertissue analysis.

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.

Mental health disorders are common during pregnancy and the postnatal period, and canhave serious adverse effects on the well-being of woman and child. Every tenth woman hasdepressive symptoms and 5% suffer major depression during pregnancy. The consequences forglobal mental health due to the novel coronavirus disease, COVID-19, are likely to besignificant and may have long-term impact on the global burden of disease. Pregnant womenmay be particularly vulnerable due to partial immune suppression. Besides physicalvulnerability, the women could be at increased risk of mental health problems, such asanxiety, depression, and post-traumatic stress disorder (PTSD), due to social distancingleading to less support from the family and friends, and in some cases, partners notbeing allowed to be present during prenatal visits, labor and delivery. Furthermore, manypregnant women may feel insecure and worried about the effect of COVID-19 on their unbornchild, if the women get infected during pregnancy. Today, young urban women are used toutilizing internet services frequently and efficiently. Therefore, providing mentalhealth support to pregnant women via web-based support may be effective in amelioratingtheir anxiety/depression and reduce the risk of serious mental health disorders leadingto improved maternal and perinatal outcomes.

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.

The purpose of the study is to confirm if BACTEK-R (MV130) provides clinical benefit insubject with mild pneumonia (CURB-65≤2) by COVID-19 admitted to the Hospital.