COVID-19 Clinical Trials and Expanded Access

The purpose of this study is to investigate whether nicotinamide riboside supplementation can attenuate the severity of SARS-CoV-2 infections in elderly patients. A major event in aging is the loss of the central metabolite nicotinamide adenine dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur during aging. Notably, recent work from our and other groups suggest that aging can be ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside. Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger state even after short term treatment. This vitamin B3- analog is naturally occurring, is readily taken up through oral administration and has been tested in human trials with few side effects. In this randomized double blinded case-control trial, the investigators will treat elderly (>70 year old) COVID19 patients with 1 g of nicotinamide riboside (NR-E) or placebo for 2 weeks and investigate if this affects the clinical course of the disease.

To date there is no brain imaging and olfactory data available in COVID-19 positive patients with anosmia. By describing the pathophysiological characteristics underlying the olfactory symptoms and clinical characteristics of COVID-19 infection, the study investigators wish to compare the MRI aspects obtained in COVID-19 patients with and without anosmia, in the absence of other underlying neurological disorders.

COVID/Homeless is a prospective observational cohort study of homeless people to determine the impact of the SARS-CoV-2 epidemic on this population. The cohort aims for exhaustiveness for the city of Marseille, being based on the active files of the partner teams, namely the four emergency shelters of Marseille and 12 outreach teams (including one specialized in psychiatry, three specialized in addictions, and three working in squats and shantytowns). Aims of this cohort include to identify of the prognostic factors of morbi-mortality of homeless people by COVID-19, and therefore to propose appropriate management strategies.

Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. At this time, there are no specific vaccines or treatments for COVID-19. However, there are many ongoing clinical trials evaluating potential treatments Drugs used to treat malaria infection has shown to be beneficial for many other diseases, including viral infections. In this Clinical trial, Investigators will evaluate the effect of Artemisinin / Artesunate on morbidity of COVID-19 patients in decreasing the course of the disease and viral load in symptomatic stable positive swab COVID-19 patients. Investigators are hypothesizing that due to the antiviral properties of this drug it will help as a treatment for the COVID -19 patients. In improving their condition and clearing the virus load,

This is an adaptive Phase I-II trial of a vaccine consisting of autologous dendritic cells previously loaded ex vivo with SARS-CoV-2 spike protein, with or without GM-CSF, to prevent COVID-19 in adults.

Sarilumab is an anti-interleukin-6 human monoclonal antibody, such as tocilizumab, which is administered subcutaneously every two weeks for the treatment of moderate to severe active rheumatoid arthritis in adult patients. Despite the effectiveness reported for tocilizumab in the recently published experiences, the need to rapidly find alternative therapies to manage the complications of Covid-19 infection remains extremely high. The lack of clinical experience on the usage of sarilumab in such patients prevents the possibility of adopting early access programs for using commercially available sarilumab (prefilled syringe) packs in patients with severe Covid-19 pneumonia. The present study is aimed to generate a rapid, still robustly documented, evidence on the potential clinical efficacy and tolerability of a further IL-6R antagonist in Covid-19 pneumonia.

Introduction There are currently no treatments with demonstrated efficacy for COVID-19 infection. Epidemiological evidence points to the existence of intrinsic protection factors which make young persons and women more resistant to the infection, whereas older patients with multiple illnesses, above all with heart disease, are at greatest risk. This trial proposes treatment initiated in the early stages of the disease, when clinical worsening is most likely, with intravenous Oxytocin (OT), an endogenous hormone currently safely used in clinical practice. The selection of this molecule is based on numerous experimental and clinical observations, which show its activity in modulating resistance to pathogens, in mitigating overall cardiovascular risk, and in acting on the production of Nitric Oxide (ON) in the lungs, which is emerging as a key therapeutic factor for the improvement of respiratory function in patients with SARS-COVID 19. Finally, OT is physiologically produced by the human body, especially in the female sex and in the age ranges that coincide with most resistant patients. In routine clinical practice, OT exhibits an excellent therapeutic index, in absence of significant adverse effects. Primary aim To assess the effects of Oxytocin in addition to standard therapy, with respect to Standard of Care (SoC), in reducing the number of patients who enter a critical stage Secondary aim To describe: - Mortality 28 days after randomization - Time to mechanical ventilation during the study - Duration of dependency on oxygen supply - Length of stay - Temporal trend of clinical improvement (7-category ordinal scale) - Safety analysis

It has been suggested that ibuprofen might be associated with more severe cases of coronavirus infections, based on the observation that severe COVID cases had been exposed to ibuprofen, resulting in a warning by the French authorities. This was attributed to: 1. a suggestion that ibuprofen might upregulate ACE-2 thereby increasing the entrance of COVID-19 into the cells, 2. an analogy with bacterial soft-tissue infections where more severe infections on NSAIDs are attributed to an immune-depressive action of NSAIDs, or to belated treatment because of initial symptom suppression, 3. fever is a natural response to viral infection, and reduces virus activity: antipyretic activity might reduce natural defenses against viruses. However fever reduction in critically ill patients had no effect on survival. However, these assertions are unclear: upregulation of ACEII would increase the risk of infection, not necessarily its severity, and would only apply to the use of NSAIDs before the infection, i.e. chronic exposure. It would be irrelevant to the infection once the patients are infected, i.e., to symptomatic treatment of COVID-19 infection. Anti-inflammatory effect masking the early symptoms of bacterial infections resulting in later antibiotic or other treatment is not applicable: there is no treatment of the virus that might be affected by masking symptoms. Antipyretic effect increasing the risk or the severity of infection would apply equally to all antipyretic agents including paracetamol, which share the same mechanism of action for fever reduction. EMA remains prudent about this assertion In addition, excess reliance on paracetamol while discouraging the use of ibuprofen might increase the risk of hepatic injury from paracetamol overdose. Paracetamol is the prime drug associated with liver injury and transplantation, in voluntary and inadvertent overdose or even at normal doses. This might be increased by COVID-related liver function alterations. It is therefore proposed to conduct a case-control study in a cohort of patients admitted to hospital in France with COVID-19 infection.

This is a small scale pilot study to evaluate if core warming improves respiratory physiology of mechanically ventilated patients with COVID-19, allowing earlier weaning from ventilation, and greater overall survival. This prospective, randomized study will include 20 patients diagnosed with COVID-19, and undergoing mechanical ventilation for the treatment of respiratory failure. Patients will be randomized in a 1:1 fashion with 10 patients (Group A) randomized to undergo core warming, and the other 10 patients (Group B) serving as the control group who will not have the ensoETM device used. Patients randomized to Group A will have core warming initiated in the ICU or other clinical environment in which they are being treated after enrollment and provision of informed consent from appropriate surrogate or legally authorized representative.

This is a monocentric retro-prospective observational study that will be conducted on all COVID19 positive patients hospitalized at the S. Gerardo Hospital in Monza.