COVID-19 Clinical Trials and Expanded Access

SUMMARY Rationale: Allied health professionals (i.e., dietitians, exercise therapists,physical therapists, occupational therapists and speech and language therapists) mightplay an important role in the recovery of patients with COVID-19 who experiencelimitations in daily physical functioning and participation. However, the evidence basefor allied healthcare in patients with COVID-19 has yet to be established. To facilitatecare for people recovering from COVID-19 and to establish this evidence base, the Dutchministry has created a temporary regulation for primary care allied healthcarespecifically for patients with COVID-19.Objective: This study is setup alongside the temporary regulation and aims to evaluatethe longitudinal recovery trajectories and related costs of patients who visited aprimary care allied healthcare professional for the management of severe symptoms andactivity limitations and/or participation restrictions related to COVID-19.Study design: Prospective cohort study. Study population: 1,315 adult patients recoveringfrom COVID-19 with severe symptoms and activity limitations and/or participationrestrictions, and who are referred to a primary care allied health professional by ageneral practitioner or medical specialist within four months of the start of the diseasewill be eligible for this study.Intervention (if applicable): Although the nature of this study is non-experimental, theallied healthcare intervention can be considered experimental due to the novelty of thedisease.Main study parameters/endpoints: The primary outcome domain of this study isparticipation measured with the Utrechtse Schaal voor Revalidatie - Participatie(USER-P). The primary endpoint is set at 6 months. A 5 point difference will beconsidered clinically relevant for patients with COVID-19.Nature and extent of the burden and risks associated with participation, benefit andgroup relatedness: There are no specific risks involved with participation in this study,as it entails the completion of questionnaires over the timeframe of one year (at thestart of the treatment, the end of the treatment, 3 months, 6 months, 9 months and 12months). The load of the survey will be highest at months 3, 6 and 12 with a total of 74survey items. Input from patient representatives suggested that this number of items wasfeasible, especially because participants are allowed to complete the survey over anumber of days. Finally, none of the items in the survey are considered emotionallydistressing. The prescribed interventions are conform the recommendations of the bestavailable evidence and are in line with usual allied healthcare interventions. Therefore,risks are likely to be negligible conform usual allied healthcare.

Investigating the role of 13cis retinoic acid in the treatment of COVID-19 andenhancement of Its spike protein based vaccine efficacy and safety.

The coronavirus disease 2019 (COVID-19) caused by the infection of severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2)，resulting in more than 82 millionconfirmed cases and caused around 1.8 million deaths, as of 2 January 2021. The ongoingpandemic still poses unprecedented global threat to public health system worldwide. OnDecember 31, 2020, the joint prevention and control agency of China Council announcedthat Sinopharm SARS-CoV-2 inactivated vaccine had been conditionally approved by NationalMedical Products Administration, and the protection rate was 79.34%. So far, more than198 vaccines were currently in preclinical or clinical development. The investigatorsaimed to initiate an observational cohort of healthy individuals injected with SARS-CoV-2Vaccine, which will perform a longitudinal, comprehensive analysis of the SARS-CoV-2vaccine Induced adaptive immune responses.

A Study of the relation of COVID-19 infection and its severity to upper and lower airwaynitric oxide, upper airway viral load and lung function.

Myocardial infarction (MI), as one of the many complications of COVID-19, is one of thecontributing patients of patients' death. This study attempts on developing anintervention of MI by regenerating damaged cardiomyocytes due to insufficiency of oxygenin cardiac muscles, triggered by an occlusion of coronary artery (MI). Heart patchdeveloped from amnion bilayer seeded with amnion epithelial stem cells and patient'sautologous cardiomyocytes is used as a therapy. Patients who undergo bypass (CABG)surgery are given heart patch, and then patients condition are observed by ECG, Echo,blood test, and radiology (technetium-99m)

The purpose of this study is to examine how patients with multiple myeloma (MM) have beenimpacted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.The study will use a questionnaire to further understand how patients are being affectedand gather information in order to track the long-term effects of the coronavirus.The scope of the questionnaire will include, COVID-19 diagnosis and treatment, changes inmyeloma treatment and care, clinical trial familiarity, health and fitness, and qualityof life.This questionnaire is a follow-on to the "MM and COVID-19" questionnaire.

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.

At least 1 in 6 COVID-19 patients admitted to hospital to receive extra oxygen will dieof complications. In patients with COVID-19, invasive treatment such as mechanicalventilation (e.g. breathing with a machine) is associated with a 50% increased risk ofdeath. Invasive treatments use a lot of healthcare resources in intensive care units andmay lead to further deaths if patients do not have access to care.The investigators aim to improve outcomes for COVID-19 patients by implementinghyperbaric oxygen therapy (HBOT). HBOT allows patients to breathe 100% oxygen in aspecial chamber at a pressure higher than sea level. It is approved by Health Canada for14 conditions. HBOT is safe when administered by experienced teams.There are two main causes of death in severe COVID-19 respiratory infections: (i) adecreased diffusion of oxygen from the lungs to the blood and (ii) an increasedinflammatory response (also called a "cytokine storm"). HBOT leads to increased oxygenlevel in blood, has strong anti-inflammatory effects, and may destroy the virusresponsible for COVID-19 disease. The initial experience with HBOT and COVID-19 fromChina, France and the United States is promising in that it prevents further worsening ofthe condition and need for intensive care.The investigators propose to test the effectiveness of HBOT for COVID-19 patients who areadmitted to hospital to receive extra oxygen. Using the most rigorous and innovativeresearch methods, this Canadian-led international study will operate at 5 centers across3 countries (Canada: Ottawa, Toronto, Edmonton; Switzerland: Geneva; UK: Rugby/London).The investigators anticipate that when treated by HBOT, COVID-19 patients needing extraoxygen to breathe will see significant health improvements as well as a decrease incomplications, inflammation in the blood, need for invasive care, death, and cost ofcare.

This research aims to investigate the incidence, clinical condition, mode of transmissionand laboratory data of women and their babies, who were exposed to COVID-19 infectionduring pregnancy. This project will consist of 4 subprojects, being that Subprojects 1and 2, will be of the observational, longitudinal type of prospective Cohort; Subproject3 will be of prevalence; Subproject 4 will be case-control. Subproject 1- This study aimsto assess periodontal condition and quality of life before and after delivery of womenwith excess weight gain or not, with exposure to coronavirus-sars-cov2. Subproject 2-Identify the proteins differentially expressed in saliva associated with COVID-19infection during the 3rd trimester of pregnancy in obese and eutrophic patients.Subproject 3- Assess the prevalence of congenital syndrome in babies associated with thepresumed maternal infection with SARS-CoV-2. Subproject 4- Case-control study in whichnewborns are submitted to clinical examination, being a group with congenitalmalformations and their respective controls and an interview with the mother was carriedout.

The main differences observed between SARSCoV-2 pneumonia and other epidemic viralpneumopathies (e.g., seasonal influenza) are the greater infectivity of SARSCoV-2, theclinical severity of the disease, particularly in young patients without co-morbidities,and the observation of radiological images related to significant parenchymal aggressionin a large number of patients.The lesions in the acute phase correspond essentially to bilateral ground glass opacitymore or less associated with condensations which would be markers of more severeinfections.The major scope of the lesions in the acute phase raises the question of whether or notthe scanning anomalies are completely resolved over time, and the possible impact on lungfunction. This risk of sequelae is very important to study given the large number ofpatients affected by SARSCoV-2, especially since these are often young patients whoappear to be "healthy".In the current context of the CoV-2 SARS pandemic, the improved quality and availabilityof diagnostic scanners provides a wealth of information on the semiology and progressionof lung disease with minimal exposure to ionizing radiation. A majority of hospitalizedpatients with SARSCoV-2 received a CT scan in the early phase of the disease. Indeed, theFrench Society of Radiology has recommended the performance of a CT scan withoutinjection in thin sections in case of suspicion or for confirmation of the diagnosis inpatients presenting initial or secondary clinical signs of severity and justifyinghospital management due to the initial lack of reagents for performing biological tests(RT-PCR) and the high sensitivity of the CT scan and its specificity in epidemic periods.The present study aims to study the kinetics of lung involvement in SARS CoV 2, to studythe predictive character of the chest CT scan performed at the patient's discharge on theexistence of radiological sequelae at 3 months but also at 1 year in order not tomisunderstand the constitution of late fibrosis after partial resolution of the CTimages. The investigatos will study the correlation between possible radiologicalabnormalities and the clinical presentation (patient symptoms and lung function). Therigorous follow-up of these patients will allow us to set up, if necessary, earlytreatment of the detected abnormalities (inhaled corticoids in case of bronchial orbronchiolar damage, study of the place of an anti-fibrosis treatment in case offibrosis,...).