COVID-19 Clinical Trials and Expanded Access

A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19)emerged at December 2019 in Wuhan, China, and soon caused a large global outbreak. Thedelayed treatment for many chronic diseases, due to the concern of SARS-CoV-2 infection,is an increasing serious problem. Here the investigators investigate the safety ofchemotherapy for patients with gynecological malignancy in Wuhan, the center of high-riskregions of COVID-19.

Evaluate HACOR socre utility and efficacy in predicting NIV and/or CPAP failure inpatients with COVID-19 associated respiratory failure.Propose adaptations to HACOR score based on the "state of art" of COVID-19

Pakistan is a resource restraint country, it's not possible to carry out coronavirustesting at mass scale. Simple cost effective intervention against the present pandemic ishighly desirable.For patients: Identifying an antiviral gargle that could substantially reduce thecolonies of COVID-19 residing in mouth and oro-naso-pharynx is likely to reduce the viralload. Such reduction in the viral load through surface debridement could aid theeffective immune response in improving the overall symptoms of the patients.For dentists: This study is important because the nature of the dental professioninvolves aerosol production, carrying out dental work on asymptomatic patients carryingcoronavirus puts the entire dental team at a great risk of not only acquiring theinfection but also transmitting it to the others. Antiviral gargles could be used bydentist and their auxiliaries as prophylaxis.For physicians and nurses: The risk of morbidity and mortality is high among physiciansand nurses involved in the screening and management of Covid-19 patients. Globally, over215 physicians and surgeons have died while taking care of Covid-19 patients. The causeof death is attributed to high exposure of viral load. The antiviral gargles and nasallavage can decrease the fatalities among doctors and nurses.Thus, patients, physicians, nurses and dentists, all could be benefited with thisfindings of this study.

In December 2019, viral pneumonia caused by a novel beta-coronavirus (Covid-19) broke outin Wuhan, China. Some patients rapidly progressed and suffered severe acute respiratoryfailure and died, making it imperative to develop a safe and effective vaccine to treatand prevent severe Covid-19 pneumonia. Based on detailed analysis of the viral genome andsearch for potential immunogenic targets, a synthetic minigene has been engineered basedon conserved domains of the viral structural proteins and a polyprotein protease. Theinfection of Covid-19 is mediated through binding of the Spike protein to the ACEIIreceptor, and the viral replication depends on molecular mechanisms of all of these viralproteins. This trial proposes to develop and test innovative Covid-19 minigenesengineered based on multiple viral genes, using an efficient lentiviral vector system(NHP/TYF) to express viral proteins and immune modulatory genes to modify dendritic cells(DCs) and to activate T cells. In this study, the safety and efficacy of this LV vaccine(LV-SMENP) will be investigated.

In December 2019, viral pneumonia (Covid-19) caused by a novel beta-coronavirus(SARS-CoV-2) broke out in Wuhan, China. Some patients rapidly progressed and sufferedsevere acute respiratory failure and died, making it imperative to develop a safe andeffective vaccine to treat and prevent severe Covid-19 pneumonia. Based on detailedanalysis of the viral genome and search for potential immunogenic targets, a syntheticminigene has been engineered based on conserved domains of the viral structural proteinsand a polyprotein protease. The infection of Covid-19 is mediated through binding of theSpike protein to the ACEII receptor, and the viral replication depends on molecularmechanisms of all of these viral proteins. This trial proposes to develop universalvaccine and test innovative Covid-19 minigenes engineered based on multiple viral genes,using an efficient lentiviral vector system (NHP/TYF) to express viral proteins andimmune modulatory genes to modify artificial antigen presenting cells (aAPC) and toactivate T cells. In this study, the safety and immune reactivity of this aAPC vaccinewill be investigated.

The novel coronavirus (SARS-CoV-2) is a new strain of coronavirus found in human in 2019,which causes epidemic worldwide. Novel coronavirus disease (COVID-19) causes acute lunginjury (ALI) and acute respiratory distress syndrome (ARDS) in patients with severeCOVID-19. Pulmonary edema is the key detrimental feature of ALI/ARDS. Autopsy of patientsdied from COVID-19 reported that, pulmonary mucus exudation was more severe and obviousthan SARS infection. Pulmonary CT scanning and pathological findings also suggest thatpulmonary edema caused by inflammatory exudation is a distinguished feature of COVID-19.Vascular endothelial growth factor (VEGF), also known as vascular permeability factor(VPF), is known as the most potent factor to increase vascular permeability, with theinduction effect 50,000 times stronger than histamine. Bevacizumab is an anti-VEGFrecombinant humanized monoclonal antibody, which has been used in anti-tumor treatmentsince 2004, with considerable reliability and clinical safety. This trial will providehigh level evidence to answer whether bevacizumab is efficacy and safe medication forpatients with severe COVID-19.

Thousands of healthcare workers have been infected with SARS-CoV-2 and contractedCOVID-19 despite their best efforts to prevent contamination. No proven vaccine isavailable to protect healthcare workers against SARS-CoV-2.This study will enroll 470 healthcare professionals dedicated to care for patients withproven SARS-CoV-2 infection. Subjects will be randomized either in the observational(control) group or in the inhaled nitric oxide group. All personnel will observe measureson strict precaution in accordance with WHO and the CDC regulations.

The study aims to investigate organ dysfunction and biomarkers in patients with suspectedor verified COVID-19 during intensive care at Uppsala University Hospital.

Modelling repurposed from pandemic influenza is currently informing all strategies forSARS-CoV-2 and the disease COVID-19. A customized disease specific understanding will beimportant to understand subsequent disease waves, vaccine development and therapeutics.For this reason, ISARIC (the International Severe Acute Respiratory and EmergingInfection Consortium) was set up in advance. This focuses on hospitalised andconvalescent serum samples to understand severe illness and associated immune response.However, many subjects are seroconverting with mild or even subclinical disease.Information is needed about subclinical infection, the significance of baseline immunestatus and the earliest immune changes that may occur in mild disease to compare withthose of SARS-CoV-2. There is also a need to understand the vulnerability and response toCOVID-19 of the NHS workforce of healthcare workers (HCWs). HCW present a cohort withlikely higher exposure and seroconversion rates than the general population, but who canbe followed up with potential for serial testing enabling an insight into early diseaseand markers of risk for disease severity. We have set up "COVID-19: Healthcare workerBioresource: Immune Protection and Pathogenesis in SARS-CoV-2". This urgent fieldworkaims to secure significant (n=400) sampling of healthcare workers (demographics, swabs,blood sampling) at baseline, and weekly whilst they are well and attending work, withacute sampling (if hospitalised, via ISARIC, if their admission hospital is part of theISARIC network) and convalescent samples post illness. These will be used to addressspecific questions around the impact of baseline immune function, the earliest immuneresponses to infection, and the biology of those who get non-hospitalized disease forlocal research and as a national resource. The proposal links directly with other ongoingISARIC and community COVID projects sampling in children and the older age population.Reasonable estimates suggest the usable window for baseline sampling of NHS HCW isclosing fast (e.g. baseline sampling within 3 weeks).

Collection and analysis of demographic, clinical, radiographic and laboratorycharacteristics of CoViD-19 patients to identify predictors of disease severity,mortality and treatment response, and to identify subgroup of patients that might benefitfrom specific therapeutic interventions