COVID-19 Clinical Trials and Expanded Access

The purpose of this study is 1) to understand effects of COVID-19 crisis on wellness of pulmonary and critical care faculty and trainees who are at frontline fighting this pandemic 2) Assess the effectiveness of series of weekly web based crisis management coaching from world renowned experts in coaching and 3) identify future areas of opportunities in physician wellness

Currently, the growing epidemic of a new coronavirus infectious disease (Covid-19) is wreaking havoc worldwide, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a RNA virus that display high similarity in both genomic and proteomic profiling with SARS-CoV that first emerged in humans in 2003 in China. Therefore, preventing and controlling the pandemic occurrences are extremely urgent as a global top priority. Due to the lack of effective antiviral drugs, patients may be treated by only addressing their symptoms such as reducing fever. Clinical autopsies from SARS-CoV-infected patients demonstrated that there were major pathological changes in the lungs, immune organs, and small systemic blood vessels with vasculitis. However, the detection of SARS-CoV were primarily found in the lung and trachea/bronchus, but was undetectable in spleen, lymph nodes, bone marrow, heart and aorta, highlighting the overreaction of immune responses induced by viral infection were really harmful, resulting in the pathogenesis of lungs, immune organs, and small systemic blood vessels. To this respect, immune modulation strategy may be potentially beneficial to enhance anti-viral immunity and efficiently reduce the viral load, improve clinical outcomes, expedite the patient recovery, and decline the rate of mortality in patients after being infected with SARS-CoV-2. Tianhe Stem Cell Biotechnologies Inc. has developed a novel globally-patented Stem Cell Educator (SCE) technology designed to reverse the autoimmune response in Type 1 diabetes (T1D), Alopecia Areata (AA) and other autoimmune diseases. SCE therapy uses human multipotent cord blood stem cells (CB-SC) from human cord blood. Their properties distinguish CB-SC from other known stem cell types, including mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC). Several clinical studies show that SCE therapy functions via CB-SC induction of immune tolerance in autoimmune T cells and restore immune balance and homeostasis in patients with T1D, AA and other inflammation-associated diseases. To correct the overreaction of overreaction of immune responses, the investigators plan to treat SARS-CoV-2 patients with Stem Cell Educator therapy.

INTRODUCTION In critical situations, such as the current COVID 19 pandemic, themes of fear, uncertainty and stigmatization are common and constitute barriers to appropriate medical and mental health interventions. These challenges, when faced by those who live with a chronic disease, such as diabetes mellitus (DM), can negatively influence quality of life and adherence to treatment, compromising the control of the disease. OBJECTIVES The present study aims to investigate the effectiveness of a tele-intervention during the COVID-19 pandemic in improving glycemic control, lipid profile, blood pressure levels and parameters of medication adherence, mental well-being and sleep quality in patients with type 1 DM and type 2 DM. METHODS A randomized clinical trial will be carried out with patients with a previous diagnosis of type 1 DM and type 2 DM, who are registered at the Hospital de Clínicas de Porto Alegre (HCPA). Inclusion criteria will be age greater than or equal to 18 years, collection of HbA1c in the HCPA laboratory in January, February or March 2020 and availability to receive weekly phone calls. Patients will be randomized, stratified by type of diabetes, in two groups: G1: participants will receive a tele-intervention by a case manager weekly to discuss topics related to diabetes management and mental well-being during the social distancing period ; G2: participants will receive the usual care. The primary outcome assessed will be the variation in HbA1c levels comparatively between groups, with or without a tele-guided strategy, after four months of social distancing (or as long as the recommendation of social distancing measures remains). Secondary outcomes will include experiencing confirmation of COVID-19 infection, variation in lipid profile, blood pressure levels and variation in parameters of emotional distress related to diabetes, eating disorders, medication adherence, symptoms minor psychiatric disorders and altered sleep patterns, which will be evaluated with specific and validated scales. According to the sample calculation, 150 patients will be included in the study (92 with type 2 DM and 58 with type 1 DM). Analysis by intention to treat will be performed separately for patients with type 1 DM and with type 2 DM. SCHEDULE The proposed experiment will start immediately after approval of this project by the research ethics committee. The duration of the proposed intervention is 4 months (or as long as the recommendation of social distancing measures remains. This means that the study may be completed before or after that period, based on national recommendations for social distancing in Brazil), with a data analysis plan and publication of the results until September 2020.

In December 2019, new coronavirus pneumonia (COVID-19) broke out in Wuhan (Hubei, China), and it spread rapidly from one city to the whole country in just 30 days, and then worldwide cases began to appear. All the countries of the world take some precautions to prevent the spread of this epidemic disease, which WHO declared as "pandemic". Apart from compulsory situations, non-home and social isolation are the primary measures. However, not leaving the house and social isolation brings with it the restriction of physical activity. According to World Health Organization (WHO), in order to obtain health benefits, adult individuals between the ages of 18-64 should perform at least 150 minutes of physical activity per week (30 minutes a day for 5 days a week) or intensive physical activity for at least 75 minutes a week. For additional health benefits, adults should increase their moderate-intensity physical activities to at least 300 minutes a week or equivalent. Physical activity; It is directly related to the prevention of chronic diseases, increasing fitness, strengthening the muscles and increasing the quality of life. It is reported that one of the ten main risk factors in terms of mortality in the world is insufficient physical activity. The effects of social isolation are related to physical inactivity, smoking and the possibility of having both health risk behaviors together. Practical and innovative interventions are needed to reduce physical performance and decrease in muscle mass, strength and physical performance in the aging population. Considering today's conditions and current COVID-19 Pandemic, technology-supported exercise programs are effective in increasing the motivation for physical activity. The purpose of this study; In order to prevent the spread of the COVID-19 pandemic, social isolation, which is one of the measures taken in our country, is to evaluate the physical activity level of adults and to investigate the effectiveness of home exercises. It is aimed to use a model based on the video supported by a home-based exercise program.

The investigators had designed weekly mindfulness sessions (details see intervention below), which is free-of-charge and will be made available to general public who feel distressed during the outbreak of COVID-19. Face-to-face delivery of mindfulness interventions was not possible due to mandatory quarantine. The investigators hypothesize that this intervention is feasible and acceptable by the participants. As secondary outcomes, the investigators also hypothesize that the intervention can reduce stress, depressive and anxiety symptoms and enhance participants' sense of coherence This will be a quasi-experimental study. Participants will be invited to fill in an online informed consent and questionnaire around 2 days before each mindfulness online session and another set of questionnaire immediately after each session (see outcome measures). Participants will be identified by their e-mail and therefore serial data could be obtained.

Research Background and Rationale In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China. An initial cluster of infections was linked to Huanan seafood market, potentially due to animal contact. Subsequently, human-to-human transmission occurred and the disease, now termed coronavirus disease 19 (COVID-19) rapidly spread within China and all over the world. A novel coronavirus, SARS-coronavirus 2 (SARS-CoV-2), which is closely related to SARS-CoV, was detected in patients and is believed to be the etiologic agent of the new lung disease. The causative agent of the current COVID-19 pandemic, SARS-CoV-2, is a single stranded positive sense RNA virus that is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV).

In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China. An initial cluster of infections was linked to Huanan seafood market, potentially due to animal contact. Subsequently, human-to-human transmission occurred and the disease, now termed coronavirus disease 19 (COVID-19) rapidly spread within China and all over the world. A novel coronavirus, SARS-coronavirus 2 (SARS-CoV-2), which is closely related to SARS-CoV, was detected in patients and is believed to be the etiologic agent of the new lung disease. The causative agent of the current COVID-19 pandemic, SARS-CoV-2, is a single stranded positive sense RNA virus that is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV).

Following the announcement of the containment of the population due to the COVID-19 epidemic on March 17, 2020 in France, a notable decrease in the number of consultations in general practice was reported. Patients no longer contact their general practitioner, including those with regular follow-up for one or more chronic conditions. This observation raised worries since it could lead to delay or failure in detecting decompensations / complications of these chronic conditions by a lack of recourse to care. Thus, an urgent message from the National Health Department (Direction Générale de la Santé - DGS) was adressed on April 8, 2020 to the health professionals regarding the organization of care aside from COVID-19. The main recommendation was "that the personal physician or the corresponding specialist should contact the most fragile patients with chronic condition to ensure follow-up and detect any risk of decompensation ". Such fragile patients are in great numbers, up to more than 200 for an average general practitioner. Therefore, although this recommendation is regarded as "essential in view of the health needs of the population", it will prove quite difficult to follow without the help of a skilled external assistance that can be quickly mobilized. The COVIQUEST project is a cluster randomized trial in general practice designed to assess the optimizationg of the screening and management of patients with chronic condition at risk of decompensation through a collaboration between the general practitioner and a medical student. The trial will focus on patients wit cardiovascular conditions aged 70 or more and patients with mental health conditions. These conditions are both highly prevalent in general practice and both at risk of severe short-term complications. Practices will be randomly assigned to a group (A or B). In group A, students will start by contacting patients with cardiovascular conditions; in group B they will start by contacting patients patients with mentral health conditions. The students will call these patients on the phone and ask them specific questions about their health, their needs, and if they want their general practitioner to call them back. The student will then transmit this information to the general practitioner who will decide on the best care to offer the patient. The primary outcome is defined as the occurrence of hospitalization during a one-month period after the phone call. It will be collected by a second phone call from the medical student. This time, all patients will be contacted, i.e. both patients with mental illness and cardiovascular patients, whatever the group. Thus, patients allocated to the control groups (i.e. patients with mental illness from group A and cardiovascular patients from group B) will also benefit from the intervention at 1 month: again, students will ask patients about their health and whether they want their general practitioner to call them back. This approach has several advantages: 1. all patients will benefit from a phone call, in accordance with the recommendations of the DGS, 2. the involvement of students, competent in medical interviews and quickly mobilizable, will help general practitioners, on the front line of many missions, without any health risk linked to the contagiousness of COVID-19 for students, 3. randomizing the call order will allow to assess with a high level of evidence the impact of such an organization on hospitalizations, for two families of diseases with high prevalence. The trial will involve at least nine French regions. Considering that the general practitioner's patient base numbers an average of 110 patients with chronic cardiovascular disease or chronic mental illness, and that at least 25 general practitioners per region participate in the study, we can expect that 22,000 patients will benefit from the intervention of this study.

Some preliminary epidemiological research conduct in China in health workers involved in the care of Covid-19 patients has shown high rates of depression (>50%), generalized anxiety disorder (>44%), insomnia (>36%) and stress symptoms (>73%), which negatively impact their well-being as well as their ability to work effectively . These rates were observed during the epidemic peak, but they can also have a long-term mental health effect, both individually, but also in a systemic manner , similar to what has been reported relative to the SARS-CoV-1 . Cognitive behavioral therapy (CBT) is recognized as an effective treatment for stress-reduction, as well as for the prevention of multiple mental health problems in at-risk individuals . Moreover, CBT has been found to be effective in brief online formats , which could make it feasible during the current Covid-19 epidemic. To our knowledge, there are no online CBT programmes targeting stress problems in health workers involved in the care of patients during the current epidemic context. The aim of our study is to evaluate the efficacy of the online CBT programme we have developped to specifically address immediate perceived stress in health workers, as well as the prevention of mental health problems at 3- and 6-months follow-up

The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide.1 As of April 14, 2020, there have been more than 1.5 million reported cases and 124 000 deaths in more than 200 countries. A recent open-label nonrandomized French study reporte that addition of azithromycin to hydroxychloroquine in 6 patients resulted in numerically superior viral clearance (6/6, 100%) compared with hydroxychloroquine monotherapy (8/14, 57%) or control (2/16, 12.5%). Azithromycin alone has never been tested, whereas azithromycin has immunomodulating and anti-inflammatory properties that could theoretically prevent or limit secondary worsening. Our hypothesis is that azithromycin combined with amoxicillin/clavulanate will be superior to amoxicillin/clavulanate alone to obtain viral clearance at Day 6 in COVID-19 patients with pneumonia and hospitalized in a non-intensive care unit ward.