Clinical Research Directory

Longitudinal At Home Smell Testing to Detect Infection by SARS-CoV-2

The purpose of this study is to learn more about how to better track smell recovery in people who have been infected with the SARS-CoV-2 virus (which causes COVID-19). Many people who have been infected by this virus develop changes in their sense of smell (olfaction). We are interested in measuring smell function objectively via smell cards that test odor intensity, identification, and discrimination. Objective and precise olfactory testing that can be performed in the convenience of one's home will help identify people with smell loss after infection by SARS-CoV-2. We will use results from this test to better understand the relationship between SARS-CoV-2 infection and recovery of olfactory function and to learn whether the AROMHA longitudinal smell test is a reliable olfactory function tracking tool to quantify smell loss in the context of COVID infection. These results may inform the design of therapeutic clinical trials to accelerate the recovery of smell function.

Cardiac Magnetic Resonance Tissue Characterization in COVID-19 Survivors

The purpose of this study is to test if visualizing the heart with cardiac MRI/echo will be important in the understanding cardiac function and prediction of cardiopulmonary symptoms, physical effort tolerance, and outcomes in COVID-19 survivors. If successful, the research will allow us to identify the causes of lasting cardiopulmonary symptoms and begin developing cardiac and lung directed therapies accordingly.

Pancoronavirus Vaccine Study in Healthy Adults

Coronaviruses (CoVs) have caused the severe acute respiratory syndrome (SARS) outbreak, the Middle East Respiratory Syndrome (MERS) outbreak, and now the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Although there are several approved or authorized vaccines for SARS-CoV-2, there are currently no vaccines approved to prevent diseases caused by multiple different coronaviruses. Two countermeasures with promise for controlling coronavirus outbreaks are recombinant neutralizing antibodies and vaccines directed against the virus. Between these two countermeasures, the ultimate solution to control the current COVID-19 pandemic and future CoV outbreaks is a pancoronavirus vaccine. In particular, a vaccine that can induce broader protection and can prevent severe disease caused by current SARS-CoV-2 variants of concern would help mitigate significant morbidity and mortality following SARS-CoV-2 infection. Additionally, an optimal pancoronavirus vaccine would prevent severe disease from other SARS-related viruses in the genus of coronaviruses-betacoronavirus-that are responsible for past outbreaks or could cause the next major outbreak in humans. Such a broadly active coronavirus vaccine would be an impactful first step towards preventing all life-threatening coronavirus human disease. The proposed vaccine immunogen (Cov-RBD-scNP-001) is composed of an engineered receptor binding domain (RBD) of SARS-CoV-2 WA-1 covalently linked in vitro to the surface of a Helicobacter pylori ferritin protein nanoparticle (RBD-scNP). The RBD has been engineered at two sites to improve its expression. The protein nanoparticle is composed of 24 individual ferritin subunits each of which can have a SARS-CoV-2 WA-1 RBD attached to it via a nine amino acid linker. The protein nanoparticle will be delivered with 3M-052-AF adjuvant - a TLR 7/8 agonist.

Passive Detection- SARS-CoV-2 (COVID-19) A&M Breathalyzer (PROTECT Kiosk) for Operational Medicine

The primary objective of this effort will be to optimize and operationalize innovative passive surveillance systems and in parallel, the effort will identify, evaluate, and transition groundbreaking new technologies in diagnostics for operationalization. To meet the objective and execute the deliverables for this program of effort, the A\&M Breathalyzer PROTECT Kiosk will be tested, modified and validated at Brooke Army Medical Center (BAMC). The collaborative efforts between the PI, Dr. Michael Morris at BAMC and Co-Investigator Dr. Tony Yuan at USU- Center for Biotechnology (4D Bio3) will assess the passive detection technology and provide a capability survey of use-case scenarios for different operational settings. Goals: 1. Optimization and operationalize the A\&M Breathalyzer PROTECT Kiosk, portable mass spectrometer (MS) Detector for Deployment in Military Operational Medicine Environments. The Breathalyzer will be deployed to BAMC to test its detection capabilities of COVID-19 among symptomatic and asymptomatic COVID-19 carrier vs. those not infected compared to gold standard RT-PCR. 2. Evaluate the passive sensing, breath capture system, built within the A\&M Breathalyzer PROTECT Kiosk. The conversion of the active breath capture system, currently requires a straw that the subject breaths into, where then a series of sensors built in the Breathalyzer would automatically sample the exhaled breath within proximity for recent COVID-19 exposure. This task would conclude with a set of sensors and sensor inputs that would be analyzed by the Atomic AI platform built in the device. Field testing at BAMC is planned to determine the level of detection and discrimination for sensor combinations to SARS-CoV2 components and biomarkers detected. This testing would update the Atomic AI algorithm, within the device, to understand the accuracy of positive detection and the resulting sensitivities.

SARS-CoV-2/COVID-19 Study of Next Generation Non-Invasive Passive Detection Technologies

The goal of this observational study is to evaluate new non-invasive passive surveillance technologies, Level 42 AI imPulse™ Una and TOR devices for the detection of COVID-19, Flu, and/or RSV in asymptomatic and symptomatic individuals over age of 18 undergoing COVID-19, Flu, and/or RSV screening and testing at BAMC Ft Sam Houston, TX; with and without COVID-19, Flu, and/or RSV. The hypotheses are: (H1) The imPulseTM Una and the imPulseTM TOR e-stethoscopes have at least a similar discriminative and detection ability among symptomatic and asymptomatic COVID-19 carrier versus those not infected compared to gold standard RT-PCR. We will operationalize and deploy both the imPulseTM Una and imPulseTM TOR e-stethoscope into DoD use-cases and compare their usability between the devices. (H2) Identify if the imPulseTM Una and the imPulseTM TOR e-stethoscopes have at least a similar discriminative and detection ability among symptomatic and asymptomatic Respiratory Syncytial Virus (RSV), Influenza and Long COVID carriers versus those not infected compared to gold standard Rapid RSV and Flu Antigen Tests, or RT-PCR and molecular assays. We will operationalize and deploy both the imPulseTM Una and imPulseTM TOR e-stethoscope into DoD use-cases and compare their captured traces in the early identification of disease/illness analyzed by the devices built in algorithms. (H3) In the mid to long-term, this approach will also be explored as a diagnostic system to explore pursue the physical (structural and mechanical) properties of cells and tissues that maintain normal cell behavior (motility, growth, apoptosis), and the critical importance of the ability of cells to sense and respond to mechanical stresses, which will be operationally critical for assessment of both traumatic and unconventional exposures in austere environments. Participants will: * Be consented; * Be screened for COVID-19, Flu, and/or RSV symptoms according to BAMC's current screening procedures; * Have study data collected; * Complete a symptoms questionnaire; * imPulseTM Una and TOR e-stethoscopes examination will be conducted; * Participants will be compensated for completing all study requirements. (Active-Duty personnel must complete the study procedures while off-duty in order to receive compensation.)

Exercise and COVID-19 Viral T-cell Immunity

Viruses are a major health problem for the general public and at risk populations. Normally, detection of antibody titers is the gold standard for determining the effectiveness of the immune system following natural or vaccine caused immunization. However, determining the effectiveness of other parts of the immune system are less common due to the difficulties with testing. Furthermore, there is a critical need to address other therapies in case vaccination is not successful in immuncompromised populations. Exercise has been shown to increase the strength of the immune system against many types of viruses and therefore could be simple way to improve immunity against the COVID-19 virus. The aim of this research is to determine the effects of exercise on anti-viral immunity against many types of common viruses before and after vaccination. We hypothesize that exercise will enhance the anti-viral immunity before and after vaccination. Up to 30 healthy volunteers (age 18-44 years) will be recruited to participate in this study. For completion of Aim 1, three visits are needed totaling around 7 hours of the patient's time and for Aim 2, three visits are needed totaling around 4.5 hours of the patient's time. The initial visit will be for pre-screening and if deemed healthy enough to participate, an exercise test to determine the VO2 max of the participant will be conducted. The following visits will require a trained phlebotomist to insert an in-dwelling catheter and participants will undergo a 20-minute incremental exercise trial. Approximately 50mL of blood will be collected at four different timepoints: at rest, 60% VO2 max, 80% VO2 max, and 1-hr post-exercise. All four collected blood samples will be used to expand viral specific T-cells and compare IFN-γ rele

Respiratory Virus Metagenomics After COVID-19

The study aims to characterize the distributive pattern of viruses in upper airway and its relationship with influenza seasons, symptomatology and exposure setting. A total of 500 adults residing in Hong Kong would be recruited, who would complete a questionnaire and return self-collected nasal and throat swabs for metagenomic analyses.

Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness

To investigate whether treatment with Azvudine reduces the risk of severe illness or death in patients who are at a potential risk of progressing to severe COVID-19 infection.

Trial of Venovenous ECMO to De-Sedate, Extubate and Mobilise in Hypoxic Respiratory Failure

To determine whether a strategy of adding venovenous ECMO to mechanical ventilation, as compared to mechanical ventilation alone, increases the number of intensive care free days at day 60, in patients with moderate to severe acute hypoxic respiratory failure.

Evolution of Respiratory Function in Lung Transplant Patients With Moderate to Severe Covid-19 Infection

The SARS-Cov-2 infection pandemic has caused a large number of acute respiratory failures and deaths across the world. Certain factors have been identified as associated with a higher risk of developing a severe form and dying. Immunosuppression has been identified as a risk factor for progressing to a severe form. Lung transplant patients were particularly vulnerable during this period, with a high frequency of respiratory compromise, sometimes progressing towards acute respiratory distress syndrome and, at a later stage, towards fibrotic forms. The impact of the infection on the immunological status of the patient and on the tolerance of the transplant have been little studied. The various treatments implemented during the pandemic have rapidly evolved (immunotherapy, vaccination, convalescent plasma transfusion, etc.) which may have modulated this risk. The evolution of respiratory function may be linked to the respiratory infection itself, or to the severity of respiratory damage during the infection. It is therefore relevant to compare patients with a moderate form of COVID-19 (non-intubated patients) to patients with severe forms, requiring invasive ventilation in intensive care. The evolution of respiratory function after infection has not yet been studied.

Efficacy and Safety Study of Essential Oil-Based Preparation Administered to COVID-19 Patients

The aim of this study was to compare the efficacy and safety of the essential oil-based product in patients with mild to moderate symptomatic COVID-19 Positive infection confirmed by PCR. A computational simulation approach of the molecular interaction (binding) of the main components of essential oils exhibiting antiviral activity with known intracellular protein targets of SARS-CoV-2 (nsp5: Main Protease) was adopted as a rationale for this study. SARS-CoV-2, a single-stranded RNA virus, has four major structural proteins Spike (S), Membrane (M), Envelope glycoprotein (E) and Nucleocapsid (N) protein and non-structural proteins (nsp). These non-structural proteins, of which there are 16 in total in the genome of the virus, play key roles in the mechanisms of the virus life cycle, including replication, transcription, protein synthesis and modification of RNA. Main protease (Main protease, Mpro, 3CLpro), virus Since they are directly involved in the maturation of these nsp proteins, which have an important role in many mechanisms of the life cycle, they have been the target enzyme in the development of new antiviral drugs for the treatment of COVID-19. In this study, our main rationale is to investigate the effect of essential oils on nsp5: Main Protease enzyme activations.

Dynamics of Markers of Infection and Inflammation in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients

Patients requiring admission to the hospital due to a moderate and severe COVID-19 infection may differ in their ability to respond to viral infection and to eliminate viral load. Several comorbidities and interventions like antivirotic or antiinflammatory treatment may also modify expected patients response and decrease of viral load. In this observational study, evolution of selected inflammatory markers, indicators of severity of infection and patient characteristics will be followed and recorded in hospitalized patients with COVID-19.

Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For COVID Pneumonia

Phase II/Phase III study to evaluate the safety and efficacy of Ramatroban 75 mg tablet against Placebo in subjects hospitalized for pneumonia due to SARS-CoV-2 infection. Approximately 324 eligible subjects will be randomized in a 1:1 ratio to one of the two treatment groups. Group I: Ramatroban 75 mg tablet + Standard of care; Group II: Placebo + Standard of care. Phase 2 Primary Objective: To evaluate the safety of Ramatroban 75 mg tablet with the standard of care against Placebo with the standard of care in COVID-19 hospitalized subjects. Secondary Objective: To assess the efficacy of Ramatroban 75 mg tablet with the standard of care against Placebo with the standard of care in COVID-19 hospitalized subjects. Phase 3 Primary Objective: To evaluate the efficacy of Ramatroban 75 mg tablet with the standard of care against Placebo with the standard of care in COVID-19 hospitalized subjects. Secondary Objective: To evaluate the safety of Ramatroban 75 mg tablet with the standard of care against Placebo with the standard of care in COVID-19 hospitalized subjects. Long COVID \[Follow-up Phase- Objectives- (Phase 2 \& 3)\] 1. To examine lipid mediators, specifically thromboxane A2, prostaglandin D2, F2-isoprostane and/or their metabolites in convalescent subjects after treatment. 2. To assess the efficacy of Ramatroban administered during the acute illness in preventing/mitigating subsequent development of long COVID / PASC