In this study we cross-reference several nationwide high-quality Swedish registers inorder to study risk factors for severe Covid-19 outcomes.

This is a randomized double-blind placebo-controlled Phase II trial of recombinant humandeoxyribonuclease I (rhDNase I) - Pulmozyme - in mechanically ventilated patients withCOVID-19 pneumonia.Patients admitted to the ICU with severe COVID-19 pneumonia who require mechanicalventilation will be invited to participate in this study. Potential subjects will beidentified from medical record review or from direct contact with physicians.Investigators will check medical history and confirm eligibility. Informed consent willbe obtained from either the patient or designated healthcare proxy.60 subjects will be enrolled. After obtaining informed consent, patients will berandomized 2:1 to Pulmozyme 2.5 mg BID for up to 28 days or until they are no longerreceiving mechanical ventilation, whichever is sooner plus standard of care vs. placebonormal saline 2.5 ml plus standard of care.

This phase I trial evaluates the side effects and best dose of GEO-CM04S1 (previouslydesignated as COH04S1), a synthetic modified vaccinia Ankara (MVA)-based SARS-CoV-2vaccine, for the prevention of COVID-19 infection. COVID-19 infection is caused by theSARS-CoV-2 virus. SARS-CoV-2 has demonstrated the capability to spread rapidly, leadingto significant impacts on healthcare systems and causing societal disruption. GEO-CM04S1was created by placing small pieces of SARS-CoV-2 DNA (the chemical form of genes) intosynthetic MVA, which may be able to induce immunity (the ability to recognize and fightagainst an infection) to SARS-CoV-2. The purpose of the Phase 1 study is to determine thesafety and the optimal dose of the GEO-CM04S1 vaccine.The Phase 2 study is designed as a multi-center, double-blind, randomized, parallel,study to evaluate the safety profile of 2 dose levels of GEO-CM04S1 as a single boostershot to assess the immune response measured by the fold-increase in antibody againstSARS-CoV-2 Spike protein at day 28 post-injection among healthy adult volunteers.

This Phase 2/3 study is a multi-portion design to confirm that the chosen formulation anddosing regimen of CoVLP has an acceptable immunogenicity and safety profile.The Phase 3 portion is an event-driven, randomized, observer blinded, placebo-controlleddesign that will evaluate the efficacy and safety of the CoVLP formulation compared toplacebo.Subjects will be followed for safety and immunogenicity for a period of 12 months afterthe last vaccination.

Despite enormous progress in understanding COVID-19, there is little evidence that asolution, therapeutic or preventive, is close to being achieved. Repurposing of wellknown, widely available drugs represent an attractive approach to speed up availabilityof active treatments. Such substances as i.e. hydroxychloroquine and others, are alreadyunder investigation and in widespread off label use. For many reasons Methylene blue(MB), the oldest synthetic substance in medicine (1876 synthesized by BASF) is such apromising candidate for an active treatment against SARS-CoV-2 infected people and forCOVID-19 patients.

COVID-19 infection was shown to cause endothelial dysfunction .At the level of the endothelium the pathophysiological mechanisms have been hypothesizedand were divided into pro-coagulant, pro-inflammatory, anti-fibrinolytics, impairedbarrier function, vasoconstrictor and pro-oxidant. So far, the pro-coagulant andpro-inflammatory pathways have been studied and as a result dexamethasone andanticoagulation became part of the standard therapies for the disease. However, so far,no RCT has been evaluated on targeting the vasoconstrictive and antioxidant pathways withan aim of revealing clinical benefit.So, with this trial we intend to provide a regiment composed of several medications wehypothesize will act on several downstream pathways that would improve endothelialfunction primarily via the increase in NO production and release.At the time of this proposal there has been no randomized trials evaluating or testingthe use of cardiovascular drugs targeting endothelial dysfunction in COVID-19 patients.As previously noted there has been a call to study these drugs and their effect after astrong research regarding their theorized effectiveness. For evidence, there was arecently published meta-analysis evaluating the role of statins in COVID-19 withpreliminary findings suggested a reduction in fatal or severe disease by 30% anddiscredited the suggestion of harm, that emphasized on the need of well-designedrandomized controlled trial to confirm the role of statins in COVID-19 patients.Our study would help determine the potential therapeutic effect of the endothelialprotocol as adjunct to mainstream management. This study seeks to further our knowledgein treating COVID-19 to ultimately improve clinical outcomes and reduce complications.

Study objective is to evaluate the efficacy of the combination of masitinib andisoquercetin in adult hospitalized patients with moderate and severe COVID-19.

With the results of this study the investigators aim to identify an effective treatmentthat will reduce morbidity and mortality of patients with symptomatic COVID-19 infection,which would in turn reduce the burden on the healthcare system by decreasing the need forintensive care.Objectives: The main objective of this research is to determine if once weekly treatmentwith the GLP-1 agonist semaglutide for 4 doses will reduce cardiac as well as non-cardiaccomplications of COVID-19 infection.Study Plan: The study design is prospective randomized open-label blinded-evaluation(PROBE). Eligible patients with symptomatic COVID-19 infection and an enhanced riskprofile as described above, who have been admitted to hospital due to symptoms ofCOVID-19 infection but do not as yet require critical care will be approached toparticipate in this study. Provided there are no exclusion criteria and the participantsagree by means of documented written informed consent, The participants the participantswill be randomized to receive s.c. semaglutide 0.25 mg s.c. or control immediately afterrandomization and then 0.5 mg s.c. at Day 7, Day 14 and Day 21. Blood will be drawn atDay 7±2 and Day 14±2 for the cardiac troponin biomarker and safety parameters. ECG willbe obtained at Day 7±2 and Day 14±2. Primary outcome will be assessed on Day 28.Primary outcome measure: A composite of (1) death from any cause or (2) mechanicalventilation (invasive or non-invasive) at 28 days.Major secondary outcome measure:(1) an elevation to >99th percentile URL upper reference limit (URL) in those with abaseline cardiac troponin level ≤99th percentile URL; or 3x elevation from baseline inthose with a baseline cardiac troponin >99th percentile URL; measured at 1 week (7-days)post randomization.Other major secondary outcome measure:A composite of 1. Death from any cause, mechanical ventilation or vasopressor or ECLS support at 28 days 2. an elevation to >99th percentile URL in those with a normal baseline troponin level; or 3x elevation from baseline in those with a baseline troponin; measured at 1 and 2 weeks (7±2 and 14±2 days) post randomization.

Study population: Patients with fibrotic lung sequelae after recovery from acute phase ofsevere COVID19 pneumonia Objectives: To evaluate the effect of pirfenidone administeredfor 24 weeks in patients who have pulmonary fibrotic changes after suffering severeCOVID19 pneumonia, analysed by - % change in forced vital capacity (FVC) - % fibrosis in high resolution computed tomography (HRCT) of the lung

Phase 2 ,double blind, randomized study of therapy with Angiotensin 1-7 in COVID-19patients. 120 confirmed SARS-CoV-2 infected patients who exhibit moderate- clinicalsymptoms including dyspnea, cough and fever, hospitalized in the KETER department inseveral hospitals in Israel, will be enrolled. 60 patients will receive Ang 1-7subcutaneously 500 mcg/kg /day. 60 patients will receive placebo : NaCl 0.9% 2 ml-control arm .Treatment duration: 14 days or until clinical improvement that enables discharge fromhospital.(the shortest time will be the limiting factor in treatment duration). Follow-up-30 days.14-30 days after discharge from hospital: we will contact the patient via phone to askquestions related to any possible adverse reaction to the drug and general health.