The study aims to investigate organ dysfunction and biomarkers in patients with suspectedor verified COVID-19 during intensive care at Uppsala University Hospital.

In December 2019, viral pneumonia caused by a novel beta-coronavirus (Covid-19) broke outin Wuhan, China. Some patients rapidly progressed and suffered severe acute respiratoryfailure and died, making it imperative to develop a safe and effective vaccine to treatand prevent severe Covid-19 pneumonia. Based on detailed analysis of the viral genome andsearch for potential immunogenic targets, a synthetic minigene has been engineered basedon conserved domains of the viral structural proteins and a polyprotein protease. Theinfection of Covid-19 is mediated through binding of the Spike protein to the ACEIIreceptor, and the viral replication depends on molecular mechanisms of all of these viralproteins. This trial proposes to develop and test innovative Covid-19 minigenesengineered based on multiple viral genes, using an efficient lentiviral vector system(NHP/TYF) to express viral proteins and immune modulatory genes to modify dendritic cells(DCs) and to activate T cells. In this study, the safety and efficacy of this LV vaccine(LV-SMENP) will be investigated.

Covid-19 has spread rapidly throughout the world causing widespread panic, death, andinjury. While this virus is the provocateur, it is often the patient's owndisproportionate immune response which deals the most devastating (and often fatal)damage. A specific part of the immune system, known as the complement, has been shown tocause such damage in other types of coronaviruses. In the SOLID-C19 study, Soliris(Eculizumab) will be used to modulate the activity of the distal complement preventingthe formation of the membrane attack complex. By modulating this portion of the immuneresponse, mortality can be halted while the patient has time to recover from the viruswith supportive medical care.

Primary Objectives: - Safety run-in Part: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with high-risk smoldering multiple myeloma (SMM) - Randomized Phase 3 Part: To demonstrate the clinical benefit of isatuximab in combination with lenalidomide and dexamethasone in the prolongation of progression-free survival when compared to lenalidomide and dexamethasone in subjects with high-risk SMMSecondary Objectives:Safety run-in Part: - To assess overall response rate (ORR) - To assess duration of response (DOR) - To assess minimal residual disease (MRD) negativity in participants achieving very good partial response (VGPR) or complete response (CR) - To assess time to diagnostic (SLiM CRAB) progression or death - To assess time to first-line treatment for multiple myeloma (MM) - To assess the potential immunogenicity of isatuximab - Impact of abnormal chromosomal subtype on participant outcomeRandomized Phase 3 Part:Key Secondary Objectives:To compare between the arms - MRD negativity - Sustained MRD negativity - Second progression-free survival (PFS2) - Overall survivalOther Secondary Objectives:To evaluate in both arms - CR rate - ORR - DOR - Time to diagnostic (SLiM CRAB) progression - Time to biochemical progression - Time to first-line treatment for MM - Impact of abnormal chromosomal subtype on participant outcome - Safety and tolerability - Pharmacokinetics (PK) - Potential of isatuximab immunogenicity - Clinical outcome assessments (COAs)

Infectious disease is the single biggest cause of death worldwide. New infectious agents,such as the SARS, MERS and other novel coronavirus, novel influenza viruses, virusescausing viral haemorrhagic fever (e.g. Ebola), and viruses that affect the centralnervous system (CNS) such as TBEV & Nipah require investigation to understand pathogenbiology and pathogenesis in the host. Even for known infections, resistance toantimicrobial therapies is widespread, and treatments to control potentially deleterioushost responses are lacking.In order to develop a mechanistic understanding of disease processes, such that riskfactors for severe illness can be identified and treatments can be developed, it isnecessary to understand pathogen characteristics associated with virulence, thereplication dynamics and in-host evolution of the pathogen, the dynamics of the hostresponse, the pharmacology of antimicrobial or host-directed therapies, the transmissiondynamics, and factors underlying individual susceptibility.The work proposed here may require sampling that will not immediately benefit theparticipants. It may also require analysis of the host genome, which may reveal otherinformation about disease susceptibility or other aspects of health status.

Thousands of healthcare workers have been infected with SARS-CoV-2 and contractedCOVID-19 despite their best efforts to prevent contamination. No proven vaccine isavailable to protect healthcare workers against SARS-CoV-2.This study will enroll 470 healthcare professionals dedicated to care for patients withproven SARS-CoV-2 infection. Subjects will be randomized either in the observational(control) group or in the inhaled nitric oxide group. All personnel will observe measureson strict precaution in accordance with WHO and the CDC regulations.

In December 2019, viral pneumonia (Covid-19) caused by a novel beta-coronavirus(SARS-CoV-2) broke out in Wuhan, China. Some patients rapidly progressed and sufferedsevere acute respiratory failure and died, making it imperative to develop a safe andeffective vaccine to treat and prevent severe Covid-19 pneumonia. Based on detailedanalysis of the viral genome and search for potential immunogenic targets, a syntheticminigene has been engineered based on conserved domains of the viral structural proteinsand a polyprotein protease. The infection of Covid-19 is mediated through binding of theSpike protein to the ACEII receptor, and the viral replication depends on molecularmechanisms of all of these viral proteins. This trial proposes to develop universalvaccine and test innovative Covid-19 minigenes engineered based on multiple viral genes,using an efficient lentiviral vector system (NHP/TYF) to express viral proteins andimmune modulatory genes to modify artificial antigen presenting cells (aAPC) and toactivate T cells. In this study, the safety and immune reactivity of this aAPC vaccinewill be investigated.

The scientific community is in search for novel therapies that can help to face theongoing epidemics of novel Coronavirus (SARS-Cov-2) originated in China in December 2019.At present, there are no proven interventions to prevent progression of the disease. Somepreliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could havebeneficial effects on SARS-CoV-2 due to the genomic similarities between this twocoronaviruses. In this study we will test whether inhaled NO therapy prevents progressionin patients with mild to moderate COVID-19 disease.

The novel coronavirus (SARS-CoV-2) is a new strain of coronavirus found in human in 2019,which causes epidemic worldwide. Novel coronavirus disease (COVID-19) causes acute lunginjury (ALI) and acute respiratory distress syndrome (ARDS) in patients with severeCOVID-19. Pulmonary edema is the key detrimental feature of ALI/ARDS. Autopsy of patientsdied from COVID-19 reported that, pulmonary mucus exudation was more severe and obviousthan SARS infection. Pulmonary CT scanning and pathological findings also suggest thatpulmonary edema caused by inflammatory exudation is a distinguished feature of COVID-19.Vascular endothelial growth factor (VEGF), also known as vascular permeability factor(VPF), is known as the most potent factor to increase vascular permeability, with theinduction effect 50,000 times stronger than histamine. Bevacizumab is an anti-VEGFrecombinant humanized monoclonal antibody, which has been used in anti-tumor treatmentsince 2004, with considerable reliability and clinical safety. This trial will providehigh level evidence to answer whether bevacizumab is efficacy and safe medication forpatients with severe COVID-19.