COVID-19 Clinical Trials and Expanded Access

Rationale In a very short time corona virus disease 2019 (COVID-19) has become a pandemicwith high morbidity and mortality. The main cause of death is respiratory failureincluding acute respiratory distress syndrome, however the exact mechanisms and otherunderlying pathology is currently not yet known. In the current setting of the COVID-19pandemic complete autopsies seem too risky due to the risk of SARS CoV-2 transmission.Yet, as so little is known, additional histopathological, microbiological and virologicstudy of tissue of deceased COVID-19 patients will provide important clinical andpathophysiological information. Minimal invasive autopsy combined with postmortem imagingseems therefore an optimal method combining safety on the one hand yet provingsignificant information on the other.This study aims to determine the cause of death and attributable conditions in deceasedCOVID-19 patients. This will be performed using post-mortem CT-scanning plus CT-guidedMIA to obtain tissue for further histological, microbiological and pathologicaldiagnostics. In addition, the pathophysiology of COVID-19 will be examined by furthertissue analysis.

Mental health disorders are common during pregnancy and the postnatal period, and canhave serious adverse effects on the well-being of woman and child. Every tenth woman hasdepressive symptoms and 5% suffer major depression during pregnancy. The consequences forglobal mental health due to the novel coronavirus disease, COVID-19, are likely to besignificant and may have long-term impact on the global burden of disease. Pregnant womenmay be particularly vulnerable due to partial immune suppression. Besides physicalvulnerability, the women could be at increased risk of mental health problems, such asanxiety, depression, and post-traumatic stress disorder (PTSD), due to social distancingleading to less support from the family and friends, and in some cases, partners notbeing allowed to be present during prenatal visits, labor and delivery. Furthermore, manypregnant women may feel insecure and worried about the effect of COVID-19 on their unbornchild, if the women get infected during pregnancy. Today, young urban women are used toutilizing internet services frequently and efficiently. Therefore, providing mentalhealth support to pregnant women via web-based support may be effective in amelioratingtheir anxiety/depression and reduce the risk of serious mental health disorders leadingto improved maternal and perinatal outcomes.

The purpose of the study is to confirm if BACTEK-R (MV130) provides clinical benefit insubject with mild pneumonia (CURB-65≤2) by COVID-19 admitted to the Hospital.

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.

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.

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 overall objective of this project is to develop an emergent treatment protocol usingadoptive T-cell therapy for the treatment of severe COVID-19. The central hypothesis isthat SARS-CoV-2 specific T cells from convalescent donors who have recovered fromCOVID-19 can be manufactured expeditiously for the treatment of severe SARS-CoV-2infections.

The goal of the research is to assess candidate COVID-19 rapid diagnostic tests (e.g.immunodiagnostic antibody tests, like Cellex qSARS-CoV-2 IgG/IgM Rapid Test, or antigentests, like Turklab Test-It COVID-19 Home Test, AllBio Science Inc. and ArtronLaboratories Inc. rapid COVID-19 antigen tests in order to judge their clinical accuracycompared to Centers for Disease Control (CDC)-recommended molecular genetic testing andclinical diagnosis. Second, it is our goal to determine if self-testing assisted byCOVIDscanDX mobile device camera acquisition software platform and telemedicineclinical/technical support (virtual point-of-care) improves the ease of use and immediateinterpretation of the tests, thus making self-testing comparable in accuracy and safetyto testing in a clinical setting. Third, we are testing antibodies to SARS-CoV-2 afterdiagnosis with COVID-19 or following vaccination to measure the onset and time course ofdetectable antibodies from finger-stick blood drops and rapid antibody lateral flowtests. The overall purpose of the study is to dramatically increase the capacity ofCOVID-19 testing by establishing the safety, ease-of-use and validity of self-testingassisted by mobile device imaging and telemedicine remote support and provide evidence ofantibody time-course response to vaccination.

In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease,identifying treatment options is critical at this time to control the disease outbreak.For this, we have designed a phase II trial of efficacy and safety with 3 branches ofdifferent combinations of treatment to identify which is the best early treatment optionfor patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options asearly as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is noapproved vaccine for the disease and the treatments being used are not specificallydesigned for the SARS-CoV-2 virus, but are different groups of drugs used for otherpathologies with mechanisms of action that justify their use because they inhibit entryof the virus into virus cells or proteases.The study aims to compare Imatinib 400mg, Baricitinib 4mg or supportive treatment,administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment.Patients who meet inclusion criteria and do not have any exclusion criteria will berandomized to receive open treatment 1:1:1