COVID-19 Clinical Trials and Expanded Access

The study will evaluate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical coronavirus disease-2019 (COVID-19), as compared to placebo, in SARS-CoV-2 seronegative adults in the double-blind phase and to describe COVID-19 outcomes, safety, and immunogenicity in the different study cohorts in open-label phase.

COVID19 patients survivors, after discharge from hospital show reduced lung function and reduced ability to exercise. Furthermore, mental health problems including stress, anxiety and depression and a low quality of life were observed. The prospective observational study involves COVID19 patients who have needed rehabilitation at the University Hospital of Ferrara. Patients receive comprehensive rehabilitation based on their specific needs in both acute and subacute rehabilitation. At the end of hospital rehabilitation, patients are offered a program to be carried out at home for both physical and psychological problems. A range of demographic and clinical data will be collected. Patients will also undergo a battery of functional, cognitive and psychological tests at 12, 26 and 52 weeks from the infection onset. Moreover, a specific assessement (both clinical and instrumental) on the pain symptom experienced, where present, will be done.

The novel coronavirus disease (COVID-19) is posing a serious challenge to the health-care systems worldwide, with an enormous impact on health conditions and loss of lives. More than 30 millions of recoveries worldwide were registered at the end of October 2020 with more than 1 million of deaths. As the disease continues to spread, strategies aimed to reduce hospitalization time in sub intensive unit care, thus reducing pressure on health system, but also to reduce some of the pathological features of COVID-19 such as inflammation and the "cytokines storm". The ketogenic diet is a high fat, low carbohydrate, adequate-protein diet that promotes a physiological ketosis (due to an increase of liver ketone bodies production). High fat, low carbohydrate diets have been shown to reduce duration of ventilator support and partial pressure carbon dioxide in patients with acute respiratory failure. Moreover, the physiological increase in plasma levels of ketone bodies exerts important anti-inflammatory and immunomodulating effects, which may reveal as precious tools to reduce potential adverse outcomes of COVID-19 disease. The hypothesis of this study is that the administration of a ketogenic diet will improve gas exchange, reduce inflammation, and the duration of hospitalization. The plan is to enrol 28 patients with diagnosis of COVID-19 hospitalized but not in ICU with SPO2 higher than 88%.

Canada is entering the important yet dangerous phase of the COVID-19 pandemic: the reopening of industry. As such, there is an urgent need for a quick and accurate screening tool to help ensure people re-entering the workplace are COVID-19 negative. This proposal offers an innovative, simple-to-implement and quick screening tool for this purpose. This study hypothesize that breathing sounds of a COVID-19 positive person would have different characteristics even if the person is asymptomatic. This study aim the development of an integrated diagnostic pattern recognition tool in the form of a smartphone app, using audio and temperature as inputs to identify COVID-19 positive individuals. The proposed digital technology will screen individuals as healthy or possibly COVID-19 positive. The latter group will then be recommended for further testing. The goal of the proposed app is to provide much more accurate early screening (currently only temperature is taken), and to reduce the burden of COVID-19 tests. This digital technology will be used and tested in Manitoba initially and later nationally in Canada, with the potential of being publicly available in the future. To use the proposed screening tool, a smartphone is held within 1 cm of an individual's mouth and the individual instructed to take five deep breaths through the mouth. The individuals' breathing sounds will be recorded by the smartphone, while the participant's temperature will also be recorded by the heat camera. The app will first use its acoustic analysis to identify sounds as healthy or abnormal. If the outcome is abnormal, then a questionnaire will be provided, along with a further acoustic analysis to rule out other common comorbid conditions (e.g. chronic lung disease). Finally, based on the inputs, the diagnostic algorithm will decide if the individual should be referred for further testing or not. Since the proposed end product is a smartphone app, the two software partner companies will play a crucial role in the final integration and development.

Examination of the prevalence of thrombosis in COVID-patients, especially in an out-patient setting. Assessment by duplex sonography. If thrombosis is detected, we will correlate it with immunity status. Assessment of health issues and cognitive function as late complication after infection.

In the context of the actual pandemia of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which requires a better diagnostic strategy for the management of patients. The study of volatile organic compounds (VOC) detected in exhaled air or in sweat, is an innovative research area for respiratory diseases. The analysis of VOC can be done either by the technique of the mass spectrometry which allows the identification of each VOC in the exhaled air or by the technique of electronic nose, simpler and faster, which provides an idea of the general profile of the VOC without identifying them. The VOC have shown their interest in some situations, such as diagnostic or prognostic tool in patients followed for thoracic tumorous pathology or bronchial or pulmonary vascular diseases. Moreover, it has recently been shown that properly trained dogs would be able to detect an olfactory signature of SARS-CoV-2 infection with a specificity greater than 90%; this olfactory signature corresponds to VOCs detectable by the flair of dogs (Nosaïs-Covid19 study). Validation of the diagnostic value of VOC analyzes by non-invasive and rapid methods (electronic nose analysis or mass spectrometry; detection by the scent of dogs) for the rapid detection and early diagnosis of a SARS-CoV-2 infection warrants the performance of this clinical study.

A double-blind, randomized, controlled, clinical trial to evaluate the efficacy and safety of MSC (mesenchymal stromal cells) intravenous administration in patients with COVID-induced ARDS compared to a control arm.

With the results of this study the investigators aim to identify an effective treatment that will reduce morbidity and mortality of patients with symptomatic COVID-19 infection, which would in turn reduce the burden on the healthcare system by decreasing the need for intensive care. Objectives: The main objective of this research is to determine if once weekly treatment with the GLP-1 agonist semaglutide for 4 doses will reduce cardiac as well as non-cardiac complications of COVID-19 infection. Study Plan: The study design is prospective randomized open-label blinded-evaluation (PROBE). Eligible patients with symptomatic COVID-19 infection and an enhanced risk profile as described above, who have been admitted to hospital due to symptoms of COVID-19 infection but do not as yet require critical care will be approached to participate in this study. Provided there are no exclusion criteria and the participants agree by means of documented written informed consent, The participants the participants will be randomized to receive s.c. semaglutide 0.25 mg s.c. or control immediately after randomization and then 0.5 mg s.c. at Day 7, Day 14 and Day 21. Blood will be drawn at Day 7±2 and Day 14±2 for the cardiac troponin biomarker and safety parameters. ECG will be obtained at Day 7±2 and Day 14±2. Primary outcome will be assessed on Day 28. Primary outcome measure: A composite of (1) death from any cause or (2) mechanical ventilation (invasive or non-invasive) at 28 days. Major secondary outcome measure: (1) an elevation to >99th percentile URL upper reference limit (URL) in those with a baseline cardiac troponin level ≤99th percentile URL; or 3x elevation from baseline in those with a baseline cardiac troponin >99th percentile URL; measured at 1 week (7-days) post randomization. Other major secondary outcome measure: A composite of 1. Death from any cause, mechanical ventilation or vasopressor or ECLS support at 28 days 2. an elevation to >99th percentile URL in those with a normal baseline troponin level; or 3x elevation from baseline in those with a baseline troponin; measured at 1 and 2 weeks (7±2 and 14±2 days) post randomization.

Children are relatively spared from the direct clinical impact of COVID-19. Pediatric patients with regular follow-up at tertiary pediatric centres and presenting one or more chronic conditions might be at increased risk for severe COVID-19. With a prospective seroprevalence study, we aim to study COVID-19 incidence, disease course and risk factors associated with SARS-CoV-2 infection in this specific context.

Non-critical patients, hospitalized within the previous 24 hours who tested positive for COVID-19 and have a prior history of cardiovascular disease (CVD) and/or significant risk factors for CVD will be treated for 28 days.