COVID-19 Clinical Trials and Expanded Access

A phase II clinical trial will be carried out with the objective of studying the impactof the administration of Tocilizumab on the evolution of the acute respiratory distresssyndrome (ARDS) in patients with severe or critical SARS-CoV-2 infection. Due to the highmortality of severe forms of SARS-CoV-2 and for ethical reasons, a control arm will notbe included. Patients will be recruited by signing an informed consent and the baselinevariables of interest will be recorded. Tocilizumab will be administered in one or twodoses, depending on the case, and will be followed up for 30 days. The response totreatment, survival and evolution will be studied. Factors associated with improvement ofARDS and survival will be identified through multivariate analyzes. The results will becompared with those reported internationally.

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 is a prospective observational registry of COVID-19 recovered patients who are nolonger symptomatic. This Registry is intended to serve as a pool of individuals that canparticipate in studies associated with serological testing, characterization of immunityand immune response, vaccine development, and convalescent plasma donors.

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

The investigators hypothesize that those with respiratory failure due to COVID-19 willhave different burdens of mental and physical disability than those with respiratoryfailure who do not have COVID-19. Detecting these potential differences will lay animportant foundation for treating long term sequelae of respiratory failure in these twocohorts.

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.

Patients presenting with the coronavirus-2019 disease (COVID-19) have a very high risk ofcardiovascular adverse events, including death from cardiovascular causes. Unfortunately,there are no reliable statistics on the frequency and severity of these complicationsduring the index hospitalization. Moreover, the long-term cardiovascular outcomes ofthese patients are entirely unknown. The investigators aim to perform a registry ofpatients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and determinetheir long-term cardiovascular outcomes.

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

The aim of this study is to evaluate the safety and efficacy of autologousadipose-derived mesenchymal cells for treating confirmed or suspected patients withSARS-CoV-2 and compromised respiratory function requiring hospitalization.The hypothesis of the Study is autologous adipose-derived mesenchymal cells given IV toeligible patients will improve clinical outcomes of COVID 19 positive patients withsevere pneumonia or ARDS by reducing or avoiding cytokine storm.