COVID-19 Clinical Trials and Expanded Access

Healthcare workers are particularly at risk of SARS-CoV-2. This study aims to assess the efficacy of a daily single dose of tenofovir disoproxil fumarate (TDF) (245 mg)/ Emtricitabine (FTC) (200 mg), a daily single dose of hydroxychloroquine (HC) (200 mg), a daily single dose of TDF (245 mg)/FTC (200 mg) plus HC (200 mg) versus placebo, during 12 weeks in: (1) reducing the incidence of symptomatic disease and (2) reducing clinical severity COVID-19 among hospital healthcare workers aged 18 to 70 years in public and private hospitals in Spain.

The mortality rate of the disease caused by the corona virus induced disease (COVID-19) has been estimated to be 3.7% (WHO), which is more than 10-fold higher than the mortality of influenza. Patients with certain risk factors seem to die by an overwhelming reaction of the immune system to the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS) and resulting in Acute Respiratory Distress Syndrome (ARDS). Several pro-inflammatory cytokines are elevated in the plasma of patients and features of MAS in COVID-19, include elevated levels of ferritin, d-dimer, and low platelets. There is increasing data that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS. Based on these data, it is hypothesized that TCZ can reduce mortality in patients with severe COVID-19 prone to CRS and ARDS. The overall purpose of this study is to evaluate whether treatment with TCZ reduces the severity and mortality in patients with COVID-19.

Recombinant human angotensin-converting enzyme 2 (rhACE2) as a treatment for patients with COVID-19 to block viral entry and decrease viral replication.

This is a Phase II interventional study testing whether treatment with hydroxychloroquine, Vitamin C, Vitamin D, and Zinc can prevent symptoms of COVID-19

Protocol bacTRL-Spike-1 will be the first-in-human study of bacTRL-Spike, and the first-in-human use of orally delivered bacTRL. Each oral dose of bacTRL-Spike contains bacterial medium with either 1 billion (Group 1A), 3 billion (Group 2A) or 10 billion (Group 3A) colony-forming-units of live Bifidobacterium longum, which has been engineered to deliver plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2.

Phase II, prospective, interventional, single-arm, multicentric, open label trial, with a parallel retrospective collection of data on not treated patients from IRCCS, San Raffaele Scientific Institute included in the institutional observational study. A sample of 50 patients with COVID-19 pneumonia will allow to detect an absolute reduction in the rate of Respiratory-failure at day+14 after treatment of 20%, assuming that the actual rate of failure in the corresponding not treated patients is 70% (alpha=5%, power=90%, two-sided test). The software PASS15 was used for calculations. The study will also include a parallel retrospective group of temporally concomitant patients from IRCCS, San Raffaele Scientific Institute, who did not receive an experimental treatment and who are enrolled in an already IRB approved observational study

The novel coronavirus SARS-CoV-2 (COVID-19) is an emerging respiratory virus that causes pneumonia. WHO data reported admission to the intensive care unit (ICU) for 6% of patients, with a mortality rate reaching 45%. To date, apart from therapeutic trials, ICU management is symptomatic, based on organ failure support therapies. In the initial phase, the therapeutic management also includes empiric antimicrobial therapy (90% of patients, in accordance with LRTI guidelines (ATS 2019) and SRLF Guidelines (2020). One challenge for the ICU physicians is the timing for discontinuation of antimicrobial treatment, especially in case of shock or ARDS, considering that a substantial proportion of COVID-19 pneumonia patients may have pulmonary bacterial coinfection/superinfection. In order to avoid unnecessary prolonged antimicrobial therapy, and subsequent selective pressure, two tests could be combined in a personalized antibiotic strategy: - Procalcitonin (PCT): PCT is a useful tool to guide antibiotics discontinuation in community-acquired pneumonia) and viral pneumonia (PMID24612487). - Respiratory multiplex PCR FA-PPP (Biomérieux®): panel has been enlarged, including 8 viruses and 18 bacteria (quantitative analysis). The turnaround time is short. Sensitivity is high (99%, PMID32179139). It may contribute, in combination with conventional tests, to accelerate and improve the microbiological diagnosis during severe COVID-19 pneumonia. The hypothesize of the study is that the combination of the mPCR FA-PPP and PCT could be used to reduce antibiotics exposure in patients with severe confirmed COVID-19 pneumonia, with a higher clinical efficacy and safety as compared with a conventional strategy.

This is a pragmatic, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection. Participants who are hospitalized and have a positive nucleic acid amplification test for SARS-CoV-2 will undergo an initial randomization in a 1:1 ratio to one of the following regimens: Arm 1: Standard of care alone Arm 2: Standard of care plus hydroxychloroquine Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy. This will effectively result in four treatment groups: 1. Standard of care alone 2. Standard of care plus hydroxychloroquine 3. Standard of care plus azithromycin 4. Standard of care plus hydroxychloroquine plus azithromycin

Prospective cohort study of COVID-19 infection among children in Norway.

The recent pandemic due to the SARS-CoV2 results in a pulmonary infection in major symptomatic patients. Because of the large number of patients and the risk of acute respiratory distress syndrome (which seems to occur in almost 5% of patients), there is a real challenge to improve physician ability to screen between patients those who will require specific surveillance and those who can be sent back home. The recent French official recommendation of the French radiology society prescribe that chest X-ray do not have any place in the COVID-19+ management whereas the WHO stipulate that ultrasound machines may be useful for these patients [1-2]. Moreover, scattered recent publications tend to stress the interest of quick ultrasound imaging for COVID-19 suspected patients for screening purpose [2-5]. The aim of this observational historico-prospective study is to assess the risk of severe clinical outcomes (admission in continuous care unit (USC), invasive respiratory assistance, death) in patients suspected or diagnosed COVID-19+ as a function of initial pulmonary ultrasound abnormalities. These clinical outcomes are assessed through phone calls at D5, D15, M1. The secondary objectives are: - Assessing the concordance between the severity of pulmonary lesions as detected by pulmonary ultrasound devices and the ones detected by CT-scanner, for patients who will undergo these two examinations. - Assessing the compared performances in detecting ultrasound pulmonary lesions for patients suspected or diagnosed COVID-19+, between an experimented operator and a newly trained operator. - Evaluate in suspected or COVID-19 patients, the risk of clinical worsening based on pulmonary ultrasound abnormalities during follow-up of hospitalized patients. - Evaluate the ultrasound evolution profiles of pulmonary lesions in patients whose clinical evolution is favorable. - Evaluate the incidence of thromboembolic events in patients who worsen secondarily.