COVID-19 Clinical Trials and Expanded Access

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.

COVID-19 has become a global problem. There is an urgent need to improve the diagnosisand screening of patients and healthcare workers for COVID-19 in the UK. Mask basedsampling is a method of detecting SARS-COV-2 (the virus responsible for COVID-19) in thebreath of suspected COVID-19 patients or healthcare workers in the mask that they wouldwear in hospital. The investigators have previously demonstrated the utility of thismethod in other respiratory infections, such as tuberculosis.This project aims to investigate the utility of mask-based sampling is a tool for thediagnosis and quantification of COVID-19 in breath and the implications in a healthcaresetting using three cohorts of participants. Initially we will compare the amount ofCOVID-19 detected by mask sampling compared with standard nasopharyngeal swab, which isthe current gold standard test, in patients who present to hospital with COVID-19symptoms.We will address the length of time COVID-19 is breathed out by people affected by thevirus and the how infectious the virus is over time in a cohort of symptomatic healthcareworkers who are isolating at home. This will allow us to understand how long someonestays infectious for and may have the potential to inform public health measures, forinstance when healthcare workers can return to work or duration of isolation. Finally wewill investigate asymptomatic carriage of COVID-19 by different healthcare workers indifferent areas of the hospital during a screening study. This will allow us tounderstand the extent of infection amongst healthcare workers and allow us to addresshospital acquired transmission.

The goal of this project is to rapidly screen promising agents, in the setting of anadaptive platform trial, for treatment of critically ill COVID-19 patients. In this phase2 platform design, agents will be identified with a signal suggesting a big impact onreducing mortality and the need for, as well as duration, of mechanical ventilation.

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.

A huge number of initiatives about COVID-19 are ongoing and a growing number ofpublications regard the correlation between cancer patients in general and SARS-CoV-2infection. Although it has been reported that cancer patients are at a higher risk ofSARS-CoV-2 infection and COVID-19 complications, data collection about cases of NENpatients SARS-CoV-2 positive are scattered and related to single countries orinstitutions. Because of that and due to the rarity and heterogeneity of NEN it will behard to have homogeneous, reliable, representative and reproducible data for drawingadequate clinical recommendations about NEN patients and COVID-19.Therefore we propose a global collection of data through an international database todescribe and monitor NEN patients with SARS-CoV-2 infection. Thisretrospective/prospective collection of data can create a solid basis to check frequenceof events, clinical management, clinical outcome, demographic, geographical, clinical andbiological correlations. This will be helpful for the clinical and scientific communityto get reliable information for a homogeneous clinical management of NEN patients duringCOVID-19 pandemic.The main goal is to get the as wide as possible representativity of the world situation.

This Phase 2 Randomized Placebo Controlled Trial will determine if administeringnebulized Dornase Alpha (rhDNase) to COVID-19 patients with respiratory failure is safeand will reduce 28-day mortality.

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

The overall objective of the study is to evaluate the safety and efficacy of MSC therapycombined with best supportive care in hospitalized patients with COVID-19.

The 2019-2020 COVID-19 pandemic is the largest outbreak in recent history. It is notknown how long after someone gets sick with COVID-19 and recovers that they can stillinfect other people. It is also not known how quickly people make antibodies against thevirus, which help clear infection from the body. The investigators will enroll 300 peoplewho had COVID-19 based on lab testing or confirmed exposure to participate. An additional25 participants who have never tested positive for COVID and have not had the vaccinewill be enrolled as negative controls. Participants will complete a survey at enrollment.The investigators will also collect blood, nose swab, saliva, stool, semen, and breastmilk to test for the virus. The investigators will ask participants to complete a surveyand give specimens up to 12 times over 24 months. This information will be used to studyhow long the virus can live in different parts of the body, antibody development, andpost-infectious complications. The investigators hope that this information will allowmedical and public health providers to make recommendations to better care for patientsin the convalescent phase of COVID-19 infection.