COVID-19 Clinical Trials and Expanded Access

Recent information appearing from different countries suggest that treatment of Coronavirus disease 2019 (COVID-19) with hydroxychloroquine or with a combination of hydroxychloroquine and azithromycin has either an indifferent effect on viral replication or substantial cardiotoxicity. This is a clinical trial aiming to prove that addition of oral clarithromycin to treatment regimen of COVID-19 is associated with early clinical improvement and attenuation of the high inflammatory burden of the host. The study will not comprise a placebo-comparator group since this is considered inappropriate in an era of a pandemic with substantial global mortality.

This is a multicenter observational retrospective cohort study that aims to study the morphological characteristics of the lung parenchyma of SARS-CoV2 positive patients identifiable in patterns through artificial intelligence techniques and their impact on patient outcome.

Prone positioning is an established intervention in mechanically ventilated acute respiratory distress syndrome (ARDS) patients, with demonstrated reductions in mortality. Preliminary data suggest that awake proning in patients with COVID-19 treated with high-flow nasal oxygenation (HFNO) improves gas exchanges, and might be associated with a reduced need of mechanical ventilation, and reduced mortality. Further investigation in a formal randomized-controlled trial is need.

In this study, the content and results of the psychiatric consultation on patients in Corona Care Ward were verified retroactively, and the effects of COVID-19 patients' emotional state and psychological support and crisis intervention were assessed on their emotional state. Patients who are admitted to the COVID-19 care unit of the Catholic University of Daegu Hospital are subject to consultation with the psychiatrist. By retrospectively reviewing the medical records of the request and the results of the subjects, We collected Socio-demographic information, medical severity (oxygen saturation, chest x-ray readings, medication being administered), clinical psychological scale (PHQ-9, GAD-7, PC-PTSD-5, AIS, P4, SF-36, SCL-90-R) This study evaluates whether there is a difference in psychological scale according to differences in socio-demographic status and medical severity, and compares psychological measures before and after referral to mental health medicine to evaluate the effectiveness of psychiatric counseling.

Sars-Cov2 has been found in the digestive tract, as well as the respiratory tract. Protection of health care workers during surgery has been increased and some guidelines advocate for abandoning laparoscopy in COVID19 patients for fear of contamination, evenghtough this does not benefit the patient. However, Sars-Cov2 contamination risk during visceral surgery remains unknown. Inadequate protection is unnecessary costful and can be inefficient if too binding. Our hypotheses are that 1) Sars-Cov 2 can travel through droplet and air during visceral surgery. 2) Laparoscopy, because of the pneumoperitoneum and its leaks, warrant more air contamination whereas laparotomy warrant more droplet contamination, which would justified increased protection.

There is compelling data indicating that there is an excessive inflammatory response in some patients with COVID-19 leading them to develop ARDS that can be severe with a very poor prognosis. Many of these patients require very long mechanical ventilation times to survive, which have led to the collapse of the health system in some regions of the world. The current evidence for the treatment of these severe forms is inconsistent and most scientific societies and governmental or international organizations recommend evaluating treatments with randomized clinical trials. Corticosteroids, being non-specific anti-inflammatory drugs, could shorten the duration of respiratory failure and improve the prognosis. Due to the lack of solid data available regarding this serious disease, our objective is to randomly evaluate the efficacy and safety of the use of dexamethasone, a parenteral corticosteroid approved in Argentina, in patients with ARDS with confirmed respiratory infection due to SARS-CoV-2 (COVID-19). After RECOVERY trial prepublication, low dose (6 mg QD for 10 days) dexamethasone was recommended as the usual care treatment for severe COVID-19. At this time only 3 patients had been included in the trial. Thus, we updated our recommendations for centers and decided to compare two different doses of this glucocorticoid for the treatment of ADRS due to COVID-19.

Selective Cytopheretic Device (SCD) treatments will improve survival in patients testing positive for COVID-19 infection diagnosed with Acute Kidney Injury (AKI) or ARDS.

Aerosol Combination therapy of All-trans retinoic acid and Isotretinoin as A novel Treatment for Inducing Neutralizing Antibodies in COVID -19 Infected Patients better than vaccine : An innovative Treatment Mahmoud ELkazzaz(1),Tamer Haydara(2), Mohamed Abdelaal(3), Ahmed M. Kabel(4), Abedelaziz Elsayed(5) ,Yousry Abo-amer(6) ,Hesham Attia(7) 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 Clinical Pharmacy, Faculty of Medicine , Tanta University,Egypt. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy,Tanta University,Egypt. 6. Hepatology,Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital,Egypt 7. Department of Immunology and Parasitology, Faculty of Science, Cairo University, Egypt. - Study Chair ((( Dr.Tamer Hydara))), Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt Contact: Dr.Tamer Hydara-Tel: 00201142233340 Mail: tamerhydara@yahoo.com - Principal Investigator ((( Mahmoud Elkazzaz))), Faculty of Science, Damietta University,GOEIC,Egypt Contact:Tel: 00201090302015 Mail: mahmoudramadan2051@yahoo.com - Study coordinator ((Prof/Dr Mohamed Abdelaal)), Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt Contact:Tel: 00201001422577 Mail: Malaal2@hotmail.com Abstract The pandemic of COVID-19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has infected over 20,000,000 people causing over 700,000 deaths .It has no currently approved treatments. In this clinical study we confirm that combination of isotretinoin and All trans retinoic acid can be used in the treatment of SARS-COV-2 better than vaccine according to the findings of previous studies and researches. Retenoic acid can induce neutralizing antibodies in case of corona virus (COVID-19) by restoring inhebited and exhausted T cells via inhebiting both CD13 and Angiotensin-converting enzyme-2 (ACE2). CD13 amyloid receptor which abundantly overexpressed on cell surface of lymphocyte, Dentritic cell, Macrophage, granulocytes and monocytes and is ubiquitous in respiratory tract epithelial cells, smooth muscle cells, fibroblasts, epithelial cells in the kidneys and small intestine, activated endothelial cells, and platelets In addition inhibing of Angiotensin-converting enzyme-2 (ACE2) , Angiotensin T1 protein and Angiotensin II-mediated intracellular calcium release pathway which is responsible for COVID-19 cell fusion and entry.ACE2-expressing cells are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication. A study demonestrated that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection, as these patients are often treated with ACE inhibitors (ACEIs) or angiotensin II type-I receptor blockers (ARBs), which have been previously suggested to increase ACE2 expression.Butisotretinoin was found to be the strongest down-regulator of ACE 2 receptors.and this will give hope for diabetic patients or patients with hypertension infected with COVID-19.Therefore we suggest that Retinoic Acid will help in inhabiting factors which may enhance antibody dependent enhancement (ADE), A phenomenon caused by covid-19 which expected to lead to failure of vaccination specially in case of corona virus (covid-19) as a hyper mutatated COVID-19 antigens can lead to (ADE) phenomenon in which IgG antibodies facilitate viral entry and fusion with infected cell through uptake of the virus-IgG complex via the Fc receptors and later viral fusion with antigen presenting cells like Dentric cells, macrophages and B cells via FcR , through the neonatal FcR instead of antibodies induced viral agglutination and this is known as antibody dependent enhancement (ADE)(2) ADE can hamper vaccine development, as a vaccine may cause the production of antibodies which, via ADE, worsen the disease the vaccine is designed to protect against. ADE in COVID-19 infection can be caused by high mutation rate of the gene that encodes spike (S) protein. In this clinical study we suggest that Hyper mutated spike protein ,lymphopenia, and impaired dentreic cells all these factors can help in and lead to delayed antibodies response and appearing after a period of covid -19 symptoms onset and this may be responsible for antibody dependent enhancement (ADE) Keywords: COVID 2019 , Retinoic acid, Lymphopenia ,T Cells, Dentric cells , ADE, Vaccine

The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of AMY-101, a potent C3 inhibitor, for the management of patients with ARDS caused by SARS-CoV-2 infection. We will assess the efficacy and safety, as well as pharmacokinetics (PK), and pharmacodynamics (PD). The study will assess the impact of AMY-101 in patients with severe COVID19; specifically, it will assess the impact of AMY-101 1) on survival without ARDS and without oxygen requirement at day 21 and 2) on the clinical status of the patients at day 21.

This is observational study to assess the prognosis of patients hospitalized with COVID-19 confirmed by RT-PCR and exposed to trimethylxanthine (TMX). Trimethylxanthine is the active molecule present in coffee. Due to the lack of etiologic treatments and considering interest about old treatments as an avenue for research, we conducted a comparative study aiming to evaluate the effect of 1,3,7-trimethylxanthine on COVID-19 infected patients. This is actually a study about methodology. The objective of this study is therefore not to demonstrate the effect of the substance on the disease but the importance of a rigorous methodology in scientific research. This project is called "Method and Teaching of Scientific Studies".