COVID-19 Clinical Trials and Expanded Access

COVID-19 (Coronavirus disease 2019) is a new infectious disease caused by a virus namedas SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus-2). Although it can have adevastating effect on many organs, the respiratory tract is particularly affected. In thecourse of the disease, a wide clinical spectrum is observed, from flu-like illness tolung failure. Some of the patients who survived the disease continue to have problemssuch as shortness of breath, fatigue, decrease in walking distance, decrease inparticipation in daily life activities. These problems suggest that the effects onrespiratory and cardiac functions continue even after the disease ends. This study wasdesigned to demonstrate the effects and extent of COVID-19 on cardiopulmonary capacity.

This is a longitudinal study of the long-term impact of COVID-19 on the lungs.Participants will be followed over a period of up to 4 years and impacts of COVID-19 onthe lungs will be measured with magnetic resonance imaging (MRI) using hyperpolarizedxenon-129, pulmonary function tests, exercise capacity, computed tomography imaging andquestionnaires.

Gazelle COVID-19 is a fluorescent lateral flow immunoassay and accompanying Readerintended for the qualitative detection of nucleocapsid antigen from SARS-CoV-2 in nasalswab specimens from individuals who are suspected of COVID-19 by their healthcareprovider within 5 days of symptom onset. The study will be conducted To obtain data tomeasure the positive percent agreement and negative percent agreement of the GazelleCOVID-19 Test compared to Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).Thestudy will assess Gazelle COVID-19 Test performance using dual mid-turbinate nasal swabsamples. This study will primarily assess Gazelle COVID-19 Test performance onsymptomatic subjects (within five days of onset of symptoms) at point of care (POC). Asubset of asymptomatic subjects will be enrolled after the symptomatic subject enrollmentis complete.

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2(SARS CoV-2), an emerging coronavirus, which has already infected 192 million people witha case fatality rate close to 2%. About 5% of patients infected with SARS CoV-2 have acritical form with organ failure. Among critical patients admitted to intensive care,about 70% of them will require ventilatory assistance by invasive mechanical ventilation(MV) with a mortality rate of 35% and a median MV duration of 12 days. The most severelung damage resulting from SARS CoV-2 infection is the acute respiratory distresssyndrome (ARDS). The virus infects alveolar epithelial cells and capillary endothelialcells leading to an activation of endothelium, hypercoagulability and thrombosis ofpulmonary capillaries. This results in abnormal ventilation / perfusion ratios andprofound hypoxemia. To date, the therapeutic management of severe SARS CoV-2 pneumonialay on the early use of corticosteroids and Interleukin-6 (IL-6) receptor antagonist,which both reduce the need of MV and mortality. The risk factors of death in IntensiveCare Unit (ICU) are: advanced age, severe obesity, coronary heart disease, active cancer,severe hypoxemia, and hepatic and renal failure on admission. Among MV patients, thedeath rate is doubled in those with both reduced thoracopulmonary compliance and elevatedD-dimer levels. Patients with severe alveolar damage are at risk of progressing towardsirreversible pulmonary fibrosis, the incidence of which still remain unknown. Thediagnosis of pulmonary fibrosis is based on histology but there are some non-invasivealternative methods (serum or bronchoalveolar biomarkers, chest CT scan). We aim toassess the incidence of pulmonary fibrosis in patients with severe SARS CoV-2 relatedpneumonia. We will investigate the prognostic impact of fibrosis on mortality and thenumber of days alive free from MV at Day 90. Finally, we aim to identify risk factors offibrosis.

Decentralized clinical study designed to collect further cough sounds, self-reportedsymptoms, and medical treatment questionnaires from participants enrolled on theCOVID-Cough Study ("Study 1").The aim of this further data collection study ("Study 2") is to: 1. develop an understanding of changes in cough sounds associated with COVID-19 and how they alter during the disease; 2. develop an understanding of other causes of COVID-19-like symptoms and their associated cough sound patterns; and 3. gain a broader understanding of the clinical outcomes of individuals who present for COVID-19 testing.

The study hypothesis is that low-dose computed tomography (LDCT) coupled with artificialintelligence by deep learning would generate imaging biomarkers linked to the patient'sshort- and medium-term prognosis.The purpose of this study is to rapidly make available an early decision-making tool(from the first hospital consultation of the patient with symptoms related to SARS-CoV-2)based on the integration of several biomarkers (clinical, biological, imaging by thoracicscanner) allowing both personalized medicine and better anticipation of the patient'sevolution in terms of care organization.

In light of the rapidly emerging pandemic of SARS-CoV-2 infections, the global populationand health care systems are facing unprecedented challenges through the combination oftransmission and the potential for severe disease. Acute respiratory distress syndrome(ARDS) has been found with unusual clinical features dominated by substantial alveolarfluid load. It is unknown whether this is primarily caused by endothelial dysfunctionleading to capillary leakage or direct virus induced damage. This knowledge gap issignificant because the initial balance between fluid management and circulatory supportappear to be decisive. On progression of the disease, bacterial superinfectionfacilitated by inflammation and virus related damage, has been identified as the mainfactor for patient outcome, but the role of the host versus the environment microbiomeremains unclear.The overarching aim of the present research proposal is to improve therapeutic strategiesin critically ill patients with ARDS due to SARS-CoV-2 infection by advancing thepathophysiological understanding of this novel disease. This research thus focuses oninflammation, microcirculatory dysfunction and superinfection, aiming to elucidate riskfactors (RF) for the development of severe ARDS in SARS-CoV-2 infected patients andcontribute to the rationale for therapeutic strategies. The hypotheses are that (I) theprimary damage to the lung in SARS-CoV-2 ARDS is mediated through an exaggeratedpro-inflammatory response causing primary endothelial dysfunction, and subsequentlyacting two-fold on the degradation of the lung parenchyma - through the primary cytokineresponse, and through recruitment of the inflammatory-monocyte-lymphocyte-neutrophilaxis. The pronounced inflammation and primary damage to the lung disrupts the pulmonarymicrobiome, leading secondarily to pulmonary superinfections. (II) Pulmonary bacterialsuperinfections are a significant cause of morbidity and mortality in COVID-19 patients.Pathogen colonization main Risk Factor for lower respiratory tract infections. Toestablish colonization, pathogens have to interact with the local microbiota (a.k.a.microbiome) and certain microbiome profiles will be more resistant to pathogen invasion.Finally, (III) Handheld devices used in clinical routine are a potential reservoir andcarrier of both, SARS-CoV-2, as well as bacteria causing nosocomial pneumonia.

The Covid-19 viral pandemic has caused significant global losses and disruption to allaspects of society. One of the major difficulties in controlling the spread of thiscoronavirus has been the delayed and mild (or lack of) presentation of symptoms ininfected individuals, and the insufficient Covid-19 testing capacity in the UK. Thiswarrants the development of alternative diagnostic tools that reliably assess Covid-19infection in the early stages of infection, while also being low- cost, low-burden, andeasily administered to a wide proportion of the population.This study aims to validate machine learning models as a diagnostic tool that predictsinfection with SARS-CoV-2 based on app-reported symptoms and phenotypic data, against the'gold-standard' swab PCR-test. This study will take place within the Covid Symptom Studyapp, the free symptom tracking mobile application launched in March 2020.

Richmond Research Institute (RRI) is applying existing and new COVID-19 PCR and antibodytests to help develop methodologies which provide fast and accurate results. Infectionwith coronavirus (SARS-CoV-2) is currently a worldwide pandemic and reliable testing forCOVID-19 is crucial to understand who is infected and therefore a risk to others byspreading the infection. RRI are currently carrying out the following tests:A. Using a membrane-based immunoassay to detect IgG and IgM antibodies to SARS-CoV-2 inwhole blood, serum or plasma specimens helps to assess whether an individual haspreviously had the virus and is potentially immuneB. Polymerase Chain Reaction (PCR) testing using an established method to check foractive SARS-CoV-2 infections.C. Quantification of anti-SARS-CoV-2 IgG and IgM antibodies in whole blood samples.The above tests are being used by RRI to follow infections (PCR) and immunity (IgG) intheir workforce, as well as their families (including children) and visitors to theirsite.Collecting this data allows the gathering of epidemiological data on SARS-CoV-2 includingincidence, prevalence, information on asymptomatic carriers and efficacy of vaccination.Furthermore, identifying individuals that are infected with SARS-CoV-2 has greatpotential to improve health outcomes by allowing infected individuals to seek the correctmedical treatment as well as self-isolate and reduce transmission.

the purpose of the study is to study the detection of SARS-Cov-2 virus in the conjunctivaof covid-19 patients and the presence or absence of conjunctivitis in these patients