COVID-19 Clinical Trials and Expanded Access

Emergent experimental and anecdotal evidence has indicated that critically ill COVID-19patients demonstrate two patient sub-types (called phenotypes). In one group the diseaseprogresses slowly and patients have a low potential of developing mild respiratoryfailure, but in the other group, an exaggerated immune response(hyper-inflammation/cytokine storm) may be linked to the onset of precipitous respiratoryfailure, termed acute respiratory distress syndrome. This syndrome is responsible for alarge portion of COVID-19 associated mortality. Thus, determining links betweenhyper-inflammation and acute respiratory distress syndrome in COVID-19 patients is ofimmediate importance. Blood samples will undergo a number of analyses to help us tounderstand as much as possible about COVID-19. We will also study any differences inphysiologic and cytokine levels before and after patients are treated withimmunomodulatory therapies as part of clinical care in COVID-19 patients.

This study seeks to determine whether the virus which causes COVID-19, SARS-CoV-2, isshed in the stools of patients who are infected.

A lot of people suffer from phobias. Phobias concerning certain diseases are not rare.This study will examine whether the COVID-19 (Coronavirus Disease) crisis was able torise phobias in people and if those with preexisting phobias or fears were more likely todevelop a phobia concerning COVID. It will look at different subtypes - physicians,medical staff, general public (not medically affiliated) and patients with psychiatricdisorders.

LIINC is a study of volunteers who were previously infected with SARS-CoV-2 (also knownas novel coronavirus or COVID-19) who have recovered from acute infection. The study isdesigned to provide a specimen bank of samples with carefully characterized clinicaldata. LIINC specimens will be used to examine multiple questions involving the virologic,immunologic, and host factors involved in COVID-19, with a focus on understandingvariability in the long-term immune response between individuals.

Assessment the Activity Value of Isotretinoin (13- Cis-Retinoic Acid ) in the Treatmentof COVID-19Mahmoud ELkazzaz(1),Tamer Haydara(2), Mohamed Abdelaal(3), Abedelaziz Elsayed(4) ,YousryAbo-amer(5), Hesham Attia(6), Quan Liu(7)' Tim Duong(8) and Heba Sahyon(9) 1. Department of chemistry and biochemistry, Faculty of Science, Damietta University, Egypt. 2. Department of Internal Medicine, Faculty of Medicine, Kafrelsheikh University, Egypt 3. Department of Cardiothoracic Surgery, Faculty of Medicine, Kafrelsheikh University, Egypt 4. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tanta University, Egypt. 5. Hepatology,Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital, Egypt 6. Department of Immunology and Parasitology, Faculty of Science, Cairo University, Egypt. 7. School of Life Sciences and Engineering, Foshan University, Laboratory of Emerging Infectious Disease, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China. 8. Montefiore Health System and Albert Einstein College of Medicine, New York, United States of America. 9. Chemistry Department, Faculty of Science, Kafrelsheikh University, Egypt. - This clinical study is the first clinical study in literature (submitted on 20 April, 2020) which demonstrated that Isotretinoin will provide complete protection against COVID-19AbstractThe COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has infected over 100 million people causing over 2.4 million deaths overthe world, and it is still expanding. There is an urgent need for targeted and effectiveCOVID-19 treatments which has put great pressure on researchers across the world fordeveloping effective drugs. In this clinical study we attempt to demonstrate Isotretinoincould be an effective and promising treatment for SARS-CoV-2 based on the intracellularmechanism of SARS-CoV-2 transmission and consequences caused. Isotretinoin could stronglyinhibit both inflammation and viral entry in severe acute respiratory syndromecoronavirus 2 infection via decreasing the overproduction of early responseproinflammatory cytokines (interleukin-6 ) which are over expressed in COVID-19 andcontributed to disease progression, poor outcomes, vascular hyper permeability andmultiorgan failure in patients infected with COVID-19. It could also block the entry ofCOVID-19 by inhibiting androgenic factors that induce serine 2 transmembrane protease(TMPRSS2) expressions.. In addition to inhibiting of Angiotensin-converting enzyme-2(ACE2), Angiotensin T1 protein and Angiotensin II-mediated intracellular calcium releasepathway which is responsible for COVID-19 cell fusion and entry, ACE2-expressing cellsare prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry andinvasion. Moreover, isotretinoin is a potential repressor and inhibitor of papain-likeprotease (PLpro), which is a lethal protein expressed by COVID-19 genes and is an enzymeof dubiquitination which facilitates virus replication in patients with COVID-19.Thegenome of Middle East Respiratory Syndrome Coronavirus is recognized by melanomadifferentiation-associated protein-5 (MDA5), retinoic acid inducible gene-1 (RIG-1) andendosomal toll-like receptor 3 (TLR3) as pathogen-associated molecular patterns. Thisrecognition resulted in the formation of type-1 interferon (IFN1). As an evasionmechanism, virus synthesize proteins that hinder the production IFN1 in the pathway.13-cis retinoic acid induced significant upregulation of toll-like receptor 3 (TLR3),mitochondrial antiviral-signaling protein (MAVS) and IFN regulatory factor 1 expressionin a time-dependent. Furthermore, 13 cis Retinoic Acid (13 cis RA) could be an effectiveand promising treatment for SARS-CoV-2 owing to its ability to increase CD4 cells andinduce mucosal IgA antibodies that are less prone to Antibody Dependent Enhancementprocess (ADE) and responsible for passive mucosal immunity in the respiratory tract. ADEis a phenomenon in which antiviral antibodies facilitate viral infection of target immunecells and, in some cases, make a second infection worse, such as dengue fever (denguevirus), By inducing IgA antibodies, 13 cis retinoic acid enhances mucosal immunity and isknown to be a potent IgA isotype.13 Cis retinoic acid induced significant upregulation oftoll-like receptor 3 an immune boosting action that may result in an immune response todsRNA intermediate leading to the production of type I IFNs which is important to enhancethe release of antiviral proteins for the protection of uninfected cells. Isotretinointherapy has furthermore proven anti-platelet and fibrinolytic activities which mayprotect patients infected with covid-19 from widespread blood clots. From this point, wesuggest that isotretinon will be the Immunity passport" in the context of COVID-19

This is a retrospective/prospective, cohort, non-interventional observational study. Thismeans that all patients with documented COVID and HM diagnosed between February 2020 andstudy initiation will compose the retrospective part, while those diagnosed after studyapproval will enter prospective part.The total duration of the study will be 12 months.The study population will must be older than 18 years of age with HM and SARS-CoV-2infection. All patients with documented SARS-CoV-2 infection (COVID) and history oractive hematological malignancies, who refer to any Hematological Unit will be included.

RACONA is a prospective trial that will test the hypothesis that nafamostat can lowerlung function deterioration and need for intensive care admission in COVID-19 patients.Design: Adult hospitalized COVID-19 patients will be randomized in a prospectivedouble-blind randomized placebo-controlled study to test the clinical efficacy ofnafamostat mesylate (administered intravenously) on top of best standard of care.Primary outcome measures: the time-to-clinical improvement, defined as the time fromrandomization to an improvement of two points (from the status at randomization) on aseven category ordinal scale or live discharge from the hospital, whichever comes first.

Since the outbreak of a syndrome of acute respiratory distress associated to a novelcoronavirus 2 (SARS-Cov2) that began in China, Europe and France have to face a sanitaryemergency with critically care support when the patient evolves to an acute respiratorydistress (ARDS). In the context of supply shortages (ventilators, bed capacities) thatcountries have to deal with, data were lacking of characteristics and outcomes ofpatients admitted to intensive care unit (ICU). the purpose of this project is to reportthe epidemiology and the outcomes of a French cohort of critically ill patients withSARS-Cov2

CORIA is an observational cohort study of immunosuppressed populations who test positivefor COVID-19. This includes people living with HIV, cancer, acquired immunodeficiencyassociated with other immunosuppressive therapy, primary immunodeficiency and recipientsof a solid organ transplant. Participants will have routine clinical data collected withoptional baseline collection and storage of a blood sample for storage . The study willbe conducted in up to 30 sites within Australia.

The study investigators are interested in learning more about how drugs, that are givento children by their health care provider, act in the bodies of children and young adultsin hopes to find the most safe and effective dose for children. The primary objective ofthis study is to evaluate the PK of understudied drugs currently being administered tochildren per SOC as prescribed by their treating provider.