COVID-19 Clinical Trials and Expanded Access

COVID-19 is associated with acute pulmonary and cardiac injury. To better understand thedegree and severity of cardiopulmonary injury as well as short and long-term sequelae ofCOVID-19 infection, this study will perform longitudinal study in patients who had recentknown diagnosis of COVID-19.

The COVID-19 (coronavirus) pandemic has had a huge impact on healthcare resources andstaff in the UK. Understanding the key risk factors associated with infection amongsthealthcare workers is essential for future pandemic response plans.Currently there are scarce data relating to the infection rates and associated factorsamongst healthcare workers in the United Kingdom (UK). Studies of infection rates inhealthcare workers have largely relied on the real-time reverse transcriptase-polymerasechain reaction (RT-PCR) test to date and it appears that Healthcare workers are twice aslikely to succumb to Coronavirus infection, when compared to the general population andthose from Black and minority ethnic (BAME) backgrounds appear to be particularly atrisk.Currently there is no evidence that the presence of SARS-CoV-2 (severe acute respiratorysyndrome coronavirus 2) antibodies provides seasonal or long term immunity to futureinfection.Therefore, this study aims to understand the current level of SARS-CoV-2 antibodypositivity and try to determine the likely risk to healthcare workers in the UK toCOVID-19 infection. This study hopes to find out whether certain individualcharacteristics will have an impact on likelihood of infection susceptibility andantibody response and determine the impact of the presence of antibodies on thelikelihood of future clinical infection over a 12 month period.The study involves an initial online survey and linkage to the recent antibody test, thena further online survey in 6 and 12 months' time. The data obtained will be linked todata that the Human Resources Department (HR) holds.Participants also have the option to partake in another antibody test at 6 and 12 months'time and linked to the data collected.

Currently, there is no approved treatment for COVID-19 in France, either for the acutephase, nor for the late chronic phase. the investigator suggest that nintedanib has thepotential to block the development of lung fibrosis when initiated early enough toinhibit the activation of mesenchymal cells and the progression of virus-inducedpulmonary fibrosis. Computerized Tomography (CT) manifestations of fibrosis or fibrousstripes are described in COVID-19 (Ye, Eur Radiol 2020). Pan et al observed fibrousstripes in 17% patients in the early phase of the disease (Pan, Eur Radiol 2020). Ye etal observed bronchiectasis in 2 patients (15.4%) and evidence of pulmonary fibrosis in 3patients (23.7%) at HRCT performed at 4 weeks (Ye, Eur Radiol 2020). Long term data arestill lacking in patients with COVID-19 and the investigators do not know how manypatients will have fibrotic sequelae from the acute illness.

The health crisis imposed by COVID-19 is forcing major worldwide social reorganizationthat will have profound consequences on our society. Currently, one-third of the world'spopulation (~3 billion individuals) is living under some kind of isolation or quarantinemeasures, causing an unprecedented and rapidly evolving psychosocial crisis.The psychosocial consequences of this health crisis will persist long after restrictionmeasures are lifted and the pandemic is over. This impact will be significant forindividuals facing unique contexts or challenges (e.g., older adults, individuals livingwith a disability, underprivileged families) and will most likely exacerbate existingsocial and gender inequalities in health and human development.There is an urgent need for information on the evolution of the psychosocial dimensionsof health and coping strategies used by our population and our health and social servicesstructures. Thus, this study is designed to accelerate the availability of high-quality,real-time evidence within health and social services structures to address, support andminimize psychosocial consequences of the COVID-19 pandemic. Through constantly evolvingresearch questions responsive to the course of the pandemic evolution, the rapid systemtransformations and adaptation of services, and knowledge users (KUs) needs, MAVIPAN aimsto address, document, monitor, and evaluate the following: 1. Individuals and families' adjustments and mitigation strategies, especially for those considered vulnerable and in high-risk contexts. 2. Healthcare and social services workers and managers' adjustments and mitigation strategies. 3. The organization of service structures. 4. The social and economic response.To achieve these objectives, we use a mixed methods study design that combinesquantitative questionnaires and qualitative interviews to deepen our understanding ofelements such as the coping strategies used during the pandemic. A first measure wastaken during lock-down as well as a follow-up at 3 months. Another follow-up will be madeat 7 months. At least one per year follow-up will be made over the course of the study (5years). Additional measures may be taken depending on the evolution of the pandemic andthe sanitary measures put in place by the authorities.

Tocilizumab is an effective treatment for severe coronavirus disease 2019 (Covid-19)pneumonia and related inflammation. Given limited global supplies, clarification of theoptimal tocilizumab dose is critical. We conducted an open-label, randomized, controlledtrial evaluating two different dose levels of tocilizumab in Covid-19 (40mg and 120mg).Randomization was stratified on remdesivir and corticosteroid at enrollment. The primaryoutcome was the time to recovery. The key secondary outcome was 28-day mortality.

This is a a randomized double blind placebo controlled Phase 2 trial with a 12 patientlead-in to evaluate safety, prior to full enrollment to an additional 28 patients (for atotal of 40 patients) to assess efficacy of decitabine in the treatment of critically illpatients with COVID-ARDS. The patients will be randomized in a 1:1 ratio to receivestandard of care plus Decitabine or standard of care plus saline based placebo. Theprimary objective is to determine safety and efficacy of decitabine for COVID-19 ARDSbased on clinical improvement on a 6-point clinical scale.

Plasma from patients who have recovered from coronavirus disease 2019 (COVID-19) isreferred to as COVID-19 convalescent plasma (CCP), and may contain antibodies againstSARS-CoV-2, the virus responsible for COVID-19. CCP infusion is being evaluated as atherapeutic or prophylactic approach in COVID-19 patients. The goal of this study is tohelp develop a bank of convalescent plasma in California, especially in medicallyunderserved communities particularly affected by the disease. In parallel, CCPadministered to COVID-19 patients will be collected and analyzed to determine whether theantibody profile correlates with clinical outcome. The purpose of this non-therapeuticstudy is to learn more about the CCP antibody profile and the effect it may have intreating COVID-19 infection.

This is a prospective cohort observational registry study that will include data on allpatients who are treated at MHS facilities for COVID-19.

COVID-19 is a community acquired pneumonia caused by infection with a novel coronavirus,SARS CoV2 and is a serious condition with high mortality in hospitalised patients, forwhich there is no currently approved treatment other than supportive care. Urgentinvestigation of potential treatments for this condition is required.This protocol describes an overarching and adaptive trial designed to provide safety,pharmacokinetic (PK)/ pharmacodynamic (PD) information and exploratory biologicalsurrogates of efficacy which may support further development and deployment of candidatetherapies in larger scale trials of COVID-19 positive patients receiving normal standardof care.Given the spectrum of clinical disease, community based infected patients or hospitalisedpatients can be included. Products requiring parenteral administration will only beinvestigated in hospitalised patients. Patients will be divided into cohorts, a)community b) hospitalised patients with new changes on a chest x-ray (CXR) or a computedtomography (CT) scan or requiring supplemental oxygen and c) hospitalised requiringassisted ventilation. Participants may be recruited from all three of these cohorts,depending on the experimental therapy, its route of administration and mechanism ofaction. The relevant cohort(s) for any given therapy will be detailed in thetherapy-specific appendix.Candidate therapies can be added to the protocol and previous candidates removed fromfurther investigation as evidence emerges. The trial will be monitored by an independentData Monitoring Committee (DMC) to ensure patient safety.Each candidate cohort will include a small cohort of patients randomised to candidatetherapy or existing standard of care management dependent on disease stage at entry.Cohort numbers will be defined in the protocol appendices.This is a Phase IIa experimental medicine trial and as such formal sample sizecalculations are not appropriate.

We aim to understand the mechanism of olfactory dysfunction in COVID-19.