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.

Covid-19, a commonly severe respiratory tract infection caused by the SARS-CoV2Coronavirus, poses an increasing threat to individual health and health care systems. Theindividual disease course ranges from mild to life threatening, the pandemic spread leadsto a shortage of health care resources including intensive care availability. It shouldbe the overarching goal to allocate sparse health care resources to those most at needand to simultaneously avoid unnecessary blocking of resources by clinically unjustifiedhospitalizations.Individuals with preexisting cardiovascular conditions are at the highest risk of healthdeterioration, even at younger age. Objective criteria for hospitalization are notimmediately available in a outpatient settings. Hence, hospitalization and emergencymedical contact is often triggered by subjectively interpreted symptoms. The goal of thisproject is thus to improve the availability of objective measurements in the outpatientsetting by means of an innovative, smartwatch mediated telemedicine approach.To achieve this goal, the investigators will conduct a randomized clinical trialcomparing a smartwatch based telemedicine intervention with standard of care. Theintervention group will receive regular objective measurements of heart rate, ECG, andSpO2 and will get access to a 24/7 medical care hotline for consultation. Theinvestigators hypothesize that the intervention group will benefit by a significantreduction in unnecessary hospitalizations and unplanned emergency medicine contacts.

The primary purpose of this study is to gain an understanding of how experiences duringthe COVID-19 pandemic, regardless of COVID-19 status, may have impacted multiple domainsof health-related quality of life and other areas such as COVID-19 specific psychologicaldistress, and disruptions to health care, finances and social interactions. We will alsoevaluate the extent to which resiliency factors such as social support, perceivedbenefits under times of stress, and ability to manage stress may buffer associationsbetween COVID-19 experiences and HRQoL. To meet these objectives, we have developed a10-minute questionnaire that taps into these areas and is based on prior work addressingconcerns of other pandemics or national crises. Participants will have previouslyconsented to protocol PA15-0336 and have provided prior lifestyle data. This will allowus to connect the COVID-19 survey data with prior existing data.

The study will follow COVID-19 patients who required intensive care after 3-6 months andone year after discharge from the ICU with functional level as well as organ function toassess recovery after COVID-19. Blood and urine will be collected for biobanking.

The purpose of this research study is 1) to conduct a prospective longitudinalsurveillance research trial, enrolling up to 200 CCHMC employees as they come back towork, and then following their clinical and laboratory parameters for up to 12 months;and 2) to support the ongoing development of diagnostic techniques for COVID-19. Theoverall goal is to investigate patterns of SARS-COV-2 infection, including immunologicalrecovery and genetic risk factors, among CCHMC employees to better understand how tosafely reintroduce the CCHMC work force back into their normal routines.

The COVID-19 crisis began in China in December 2019 and was declared a pandemic by theWorld Health Organisation on March 11th 2020. The pandemic has changed the way thatclinicians interact with and treat patients overnight. Staff within the NHS will be underhigh levels of stress due to the increased needs and worse outcomes of work as they areshielding or self-isolating and may feel helpless and guilty. The psychological impact ofthe pandemic will be prolonged and varied. It is vital that Investigators increaseunderstanding as much as possible to support NHS staff.The aim of this survey is to examine the possible mental health burden on NHS staff as aresult of the COVID-19 pandemic and how these change as the pandemic progresses. Byunderstanding these effects, it will allow researchers to identify recommendations toallow support mechanisms to be put in place for NHS staff, to better manage this andfuture pandemics and similar crises.Investigators are aiming to sample several cohorts of NHS staff including a subset ofstaff who are shielding. Staff will be asked to complete a series of online surveys atmultiple timepoint: on study initiation, 1 month later and then 3 months after thepandemic has ceased in the UK. Additional timepoints may be added depending on the lengthand severity of the pandemic.The main outcomes will be tracking changes in mental health measurements at thepre-defined timepoints. This work will allow Investigators to produce recommendationsabout the increased mental health support that NHS staff will need. If a need isdemonstrated then an interventional research project will be designed and implemented.

This is a prospective, randomized, single-center, open-label controlled trial, designedto compare the efficacy of two ventilation strategies (Low Tidal Volume and positiveend-expiratory pressure (PEEP) based on the Acute Respiratory Distress Syndrome (ARDS)Network low PEEP-fraction of inspired oxygen inspired oxygen fraction (FIO2) Table versusLow Driving Pressure and PEEP guided by Electrical Impedance Tomography (EIT) in reducingdaily lung injury score in patients with acute respiratory distress syndrome caused byCOVID-19. The two strategies incorporate different prioritizations of clinical variables.The PEEP-FIO2 table strategy aims to reduce lung overdistension, even if it requirestolerating worse gas exchange. EIT-guided strategy prioritizes mechanical stressprotection, avoiding alveolar overdistension and collapse.

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.

To respond to the COVID-19 pandemic, investigators will be deploying community healthworkers, equipped with mobile technology, and accompanied by youth to visit householdsdoor to door to screen for symptoms of COVID-19, isolate, test, and manage suspectedcases of COVID-19. The community health workers and youth will educate households aboutpreventive measures including frequent handwashing and home management of mild cases.Simultaneously, investigators will work with nurses, doctors, and clinical officers, totest and treat more severe cases of COVID-19 in health facilities. Our goals are: tovisit every household in Siaya county covering a population of close to 1 million, and totrain and support health workers working in 32 health facilities with oxygen capacity inSiaya to reduce the morbidity and mortality related to COVID19 and other conditions.

Sex and gender matter to health equity, especially in a pandemic. Sex (a biologicalattribute) and gender (a social construct) may influence an individual's susceptibility,vulnerability and exposure to infectious disease. In previous coronavirus epidemics (SARSand MERS), male sex was associated with worse outcomes. Both immune and the hemostaticresponse display ample sexual dimorphism.The primary aim of the study is to determine whether sex differences in biomarkers ofplatelet and immune function, gut microbiome, clinical characteristics, therapy, clinicalcost sensitive outcomes (i.e. in-hospital transition of care, case severity, andmortality due to COVID-19) exist in patients affected by COVID-19.