COVID-19 is a disease caused by the virus, SARS-CoV-2. Patients with this viral infection are at risk for developing pneumonia and acute respiratory distress syndrome (ARDS). Approximately 20% to 30% of hospitalized patients with COVID-19 and pneumonia require intensive care for respiratory support. Clinically, ARDS presents with severe hypoxemia evolving over several days to a week in combination with bilateral pulmonary infiltrates on chest X-ray. Widespread alveolar epithelial cell and pulmonary capillary endothelial injury can lead to severe impairment in gas exchange. In one report of 1,099 patients hospitalized with COVID-19, ARDS occurred in 15.6% of patients with severe pneumonia. In a smaller case series of 138 hospitalized patients, ARDS occurred in 19.6% of patients and in 61.1% of patients admitted to an intensive care unit (ICU). To date, no effective treatment has been established to treat COVID-19 or to prevent progression of ARDS. It is thought that a heightened immune response with an unbalanced release of inflammatory mediators in the airway is a major cause of morbidity and mortality associated with the disease. It is therefore reasonable to postulate that improved outcomes may be obtained in patients with a balanced immune response with adequate viral control and appropriate counter-regulatory immune responses whereas a poor outcome may be expected in patients with inadequate viral control or a heightened immune response or what is referred to as a "cytokine storm". Thus, modulating the pulmonary immune response without suppressing the immune system would be a viable strategy for patients with COVID-19. The current literature supports the role of neuromodulation, particularly vagal nerve stimulation (VNS), in modulating the immune response. Modulating the pro-inflammatory pathway through VNS has been demonstrated to decrease inflammatory mediators and improve outcomes in several animal models and in humans. Percutaneous electrical nerve field stimulation (PENFS) provides a novel, non-invasive method of VNS through a non-implantable device applied to the external ear. Already, the FDA has cleared this technology for reducing symptoms of opioid withdrawal in patients with opioid use disorder. Symptoms of opioid withdrawal can be decreased by approximately 90% after 1 hour of stimulation. Similarly, the IB-Stim device has been shown to improve symptom in children with abdominal-pain-related functional GI disorders and recently received market approval by the FDA for that indication. Unpublished studies have demonstrated marked decrease in inflammation with PENFS compared to sham stimulation in a model of TNBS colitis. While the efficacy of PENFS in modulating the progression of pulmonary disease in patients with COVID-19 is unknown, several proposed mechanisms for regulation of the immune response through VNS have already been demonstrated. We propose to perform an open label, randomized study to evaluate the efficacy of PENFS for the treatment of respiratory symptoms in patients with COVID-19.

Type: Interventional

Start Date: Jul 2020

open study

This project will test the efficacy of fluoxetine to prevent serious consequences of COVID-19 infection, especially death. Becoming sick with COVID-19 virus or any other serious respiratory condition is not fun. However, the dramatic effects of the COVID-19 pandemic on human society stem from its significant mortality, not the number of individuals who become sick. This project aims to prevent serious outcomes such as hospitalization, respiratory failure and death during the time it takes to develop vaccinations and other strategies to prevent COVID-19 infectionPoor outcomes with COVID-19 infection such as hospitalization, respiratory failure, organ failure and death are associated with a dysfunctional exaggerated immune response, called a cytokine storm, that is triggered by Interleukin-6 expression (IL-6) and seems to occur around day 5 to 7 of symptoms. Fluoxetine has extraordinarily strong evidence in its action as a blocker of IL-6 and cytokine storms in both animal models of infection and in human illness such as rheumatoid arthritis and others. This action of fluoxetine is an entirely separate pathway than the serotonergic pathway that allows fluoxetine to act as an antidepressant. This pathway has been demonstrated in cell culture, in animal models, in human illness and by novel bioinformatics analyses of protein transcripts to be relatively unique for fluoxetine and appears to be a novel pathway. This project aims to inhibit the increase in IL-6 expression and thereby prevent the cytokine storm that causes poor outcomes. Patients who have tested positive or are presumptively positive for COVID-19 will be entered into the study and given the option to start the medication fluoxetine, which is demonstrated to prevent IL-6 surges in infectious and inflammatory conditions. Participants will be monitored daily for COVID-19 symptoms and weekly for side effects and tolerance of fluoxetine. A subset of patients will have blood drawn weekly and stored to monitor IL-6 and other cytokine levels at a later date. This project aims to reduce the serious outcomes of COVID-19 infection by preventing or inhibiting the cytokine storm associated with organ failure, respiratory failure and death.

Type: Interventional

Start Date: May 2020

open study

This is a Phase 2/3 open-label study to evaluate the safety and immunogenicity of a booster dose of the XBB.1.5 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant (r) spike (S) protein nanoparticle vaccine (SARS-CoV-2 rS) adjuvanted with Matrix-M™ in previously mRNA COVID-19 vaccinated adult participants ≥18 years of age and baseline SARS CoV-2 seropositive COVID-19 vaccine naïve participants ≥18 years of age.

Type: Interventional

Start Date: Sep 2023

open study

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.)

Type: Observational

Start Date: May 2023

open study

Open label clinical trial of persons (adults) that will determine the safety and efficacy of the diet supplement oral mitoquinone/mitoquinol mesylate (Mito-MES) to prevent the development and progression of severe viral infections like COVID-19 after high-risk exposure to a person with possible respiratory viral infection such as SARS-CoV-2 infection in persons who will receive Mito-MES compared to persons who will not receive Mito-MES (controls).

Type: Interventional

Start Date: Apr 2022

open study

This randomized, double-blind, placebo-controlled, Phase 1b study evaluates the safety and tolerability, and effects on cytokine and acute phase reactants of SP16, an anti-inflammatory drug, in patients with pneumonia due to SARS-CoV-2 infection. The study will enroll up to 20 patients and each eligible patient will be randomized to receive either one of two doses of SP16 (6 mg or 12 mg) or placebo by subcutaneous injection.

Type: Interventional

Start Date: Dec 2021

open study

The purpose of this research study is to learn about the factors parents consider when deciding whether their child will go to school in-person or attend from home. Investigators are also interested in learning whether access to in-home COVID testing is of value to parents and also whether it affects decision-making about returning to school. This study is being done at UW-Madison in partnership between the Department of Pediatrics and the Department of Industrial and Systems Engineering. A total of 50 caregivers (plus their children with medical complexity) will participate in this study. Additionally, 20 caregivers involved in the study may also be invited to participate in a one-hour, virtual visit in which the caregiver demonstrates and discusses how they perform in-home COVID testing with their child. The results of the study may help researchers advance their understanding of in-home testing strategies for children with medical complexity.

Type: Interventional

Start Date: Apr 2021

open study

This is an open-label study to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1273 Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) vaccine in adults with a kidney or liver solid organ transplant (SOT) and in healthy adult participants. The primary goal of the study is to evaluate the safety of mRNA-1273 and the serum antibody (Ab) responses obtained 28 days after the last dose of mRNA-1273.

Type: Interventional

Start Date: Apr 2021

open study

The purpose of this study is to identify the number of individuals with severe CoVID who require ventilator support and who develop serious fungal infections. The study is an observational study, meaning that we are not providing any intervention that does not involve usual standard of care. Our chief goal is to find evidence of fungal infection by using traditional, approved methods of diagnosis, but by applying these methods in the same way and frequency among all study participants. We will be looking especially for evidence of a fungal infection known as Aspergillus, which can causes a serious lung infection called invasive aspergillosis (IA).

Type: Observational

Start Date: Mar 2021

open study

Randomized, double-blind prospective trial to test the efficacy of therapeutic, antiseptic mouth rinses to inactivate severe acute respiratory syndrome coronavirus (SARS-CoV-2) in saliva of COVID-19 positive patients aged 18-65 years old. All mouthrinses are commercially available and will be used according to on-label instructions. Patients will be randomized to a mouthrinse and will be asked to give a saliva sample immediately before and after a one minute mouthwash. Saliva samples will be collected from patients at 15 minute intervals thereafter up to an hour (15, 30, 45 and 60 minutes). The samples will be stored and used for real-time reverse transcription polymerase chain reaction (RT-PCR) detection of viral SARS-CoV-2 RNA and viral infectivity assays. Patients will also complete a short-survey on the taste and experience of using the mouthwash. This study involves 150 subject participants and one, 75-90 minute visit.

Type: Interventional

Start Date: Jan 2022

open study

The long-term goal of the study is to mitigate the spread of the pandemic in miners, a population of high-risk, rural essential workers who are susceptible and vulnerable to COVID-19, partly based on exposure to particulate air pollution, and who are predominantly racial/ethnic minorities in New Mexico (NM) (3, 11). The study objective is to provide proof-of-principle for frequent point-of-care molecular testing as a workplace surveillance tool to monitor and prevent the spread of SARS-CoV-2 infection in this unique population. The central hypothesis is that frequent workplace molecular surveillance is an effective method to reduce SARS-CoV-2 infection and discover novel host risk factors for the virus. The site of molecular surveillance (intervention site) will be a surface coal mine in McKinley County, NM, located just outside the Eastern Agency of the Navajo Nation, comprised of 66% minority miners. This site offers a unique opportunity for a community-based study of SARS-CoV-2 infection in this population. Miners at the intervention site will provide nasal swabs before beginning their work shift on alternate days that will be analyzed with a 'screening' molecular test (12). This test is ideal because it is low cost, simple, portable, point-of-care, rapid, and can be performed by minimally trained professionals in low-infrastructure settings. The control site is a similar coal mine in Campbell County, Wyoming (WY). Both mines, operated by the same company, have similar engineering, administrative, and personal protective measures in place. The rationale for this study is to establish the suitability of longitudinal molecular surveillance to prevent and control SARS-CoV-2 infection in this unique population by completing the following specific aims.

Type: Interventional

Start Date: Feb 2021

open study

A Phase 1/2 study of agenT-797 to treat moderate to severe acute respiratory distress syndrome (ARDS) secondary to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza.

Type: Interventional

Start Date: Sep 2020

open study

The purpose of this study is to measure how well LY3819253 and LY3832479 work against the virus that causes COVID-19. LY3819253 and LY3832479 will be given to participants with early symptoms of COVID-19. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 weeks and includes one required visit to the study site, with the remainder of assessments performed in the home or by phone. Pediatric participants, with mild to moderate COVID-19 illness, will enroll in a single-arm (Arm 22), open-label addendum to evaluate the pharmacokinetics and safety of LY3819253 and LY3832479. Enrollment began on March 31, 2021, and completed on September 24, 2021. Pediatric participants, with mild to moderate COVID-19 illness, will enroll in a single-arm (Arm 23), open-label addendum to evaluate the pharmacokinetics and safety of LY3853113. Enrollment began on August 19, 2022, and completed on February 21, 2023.

Type: Interventional

Start Date: Jun 2020

open study

This is a phase 1b randomized, double-blind, placebo-controlled study in adult subjects with Coronavirus Disease 2019 (COVID-19). This clinical trial will evaluate the preliminary safety and efficacy of BM-Allo.MSC vs placebo in treating subjects with severe disease requiring ventilator support during COVID 19 infection.

Type: Interventional

Start Date: Aug 2020

open study

Randomized, placebo controlled study to determine if nebulized heparin may reduce the severity of lung injury caused by the novel coronavirus, also known as COVID-19

Type: Interventional

Start Date: Jun 2020

open study

The primary goal of this study is to evaluate the safety and reactogenicity of multi-component vaccines mRNA-1045 (Influenza and RSV) and mRNA-1230 (influenza, RSV, and SARS-CoV-2) compared with mRNA-1010 (influenza), mRNA-1345 (RSV), and mRNA-1273.214 (SARS-CoV-2) vaccines in healthy older participants.

Type: Interventional

Start Date: Oct 2022

open study

The purpose of this study is to evaluate the performance of the Bio-Self COVID-19 Antigen Home Test. The study will evaluate the accuracy (sensitivity and specificity) in a simulated home use environment when compared to a high-sensitivity Emergency Use Authorization (EUA) SARS-CoV-2 RT-PCR assay.

Type: Interventional

Start Date: May 2022

open study

Prevention of COVID-19 caused by SARS-CoV-2.

Type: Interventional

Start Date: Mar 2022

open study

In this Phase 4, open-label trial, participants of the ACTIV-3/TICO clinical trial at selected sites who received certain pre-specified blinded investigational agents or placebo as part of that trial, and who have since achieved sustained recovery, and who are still [TICO assignment] blinded and who are still within 28 to 90 days after initial TICO randomization, will be randomized in this 2x2 factorial design to one of four groups: (i) immediate versus 12 week deferral of first dose administration and also (ii) one dose only, versus two doses to be given 4 weeks apart of the Moderna mRNA-1273 or the Pfizer BNT162b2 vaccine (mRNA vaccines). Choice of Moderna or Pfizer vaccine is determined based on availability at the site. The choice is individual, although participants vaccinated twice should receive the same type of vaccine for both injections. The primary objectives of this 2x2 factorial design are (i) to estimate the difference in neutralizing antibody (NAb) response to the mRNA vaccine from baseline to Week 48 among participants vaccinated early versus deferred, and (ii) to estimate the difference in NAb response to this vaccine among participants vaccinated once versus twice. The primary analyses will be carried out in participants randomized to placebo in TICO. Analyses will also be carried out for those who receive the investigational agent(s) studied in TICO. A key secondary objective is to ascertain the effect, if any, of SARS-CoV-2 monoclonal antibodies, and other interventions that have been studied in hospitalized COVID-19 subjects, on natural and vaccine-induced immunity. Participants will remain blinded to the interventions received in the ACTIV-3/TICO study, however allocation to the timing of vaccination and to one or two vaccinations in this (VATICO) study is not blinded.

Type: Interventional

Start Date: Aug 2021

open study

In this work, the investigators are partnering with Contra Costa Health Services (CCHS), the department of health in Contra Costa County, CA, to measure COVID-19 vaccinations and other COVID-19 related preventive health behaviors in the county's Medicaid managed care population. This work will test ways to increase COVID-19 vaccine uptake. The investigators hypothesize that small financial incentives and other low-cost behavioral nudges can be used to increase vaccine uptake and reduce disparities in uptake among diverse racial/ethnic minority populations.

Type: Interventional

Start Date: May 2021

open study

The purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injections in subjects experiencing prolonged symptoms (> 12 weeks) of COVID-19.

Type: Interventional

Start Date: Mar 2021

open study

Double-blinded, placebo control, randomized, phase-3 clinical trial to evaluate clinical efficacy of Favipiravir in patients with mild to moderate symptoms related to COVID-19 infection

Type: Interventional

Start Date: Nov 2020

open study

The study will analyze the incidence, clinical outcomes and predictors of myocardial injury in a large patient population with COVID-19 treated in Mount Sinai Hospital (MSH) system. In addition, the study team will explore the association between high-sensitivity troponin I (TnI) levels and clinical characteristics, biomarkers, cardiac tests data and treatment approaches to uncover the potential mechanisms responsible for COVID-19 induced myocardial injury.

Type: Observational

Start Date: May 2020

open study

We aim to better understand the mode of action of COVID-19 in the context of its interaction with the host genome through whole-genome sequencing.

Type: Observational

Start Date: Aug 2020

open study

This study will evaluate the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.

Type: Interventional

Start Date: Dec 2020

open study