Clinical Research Directory

T-Lymphocytes for Prevention or Treatment of Viral Infections Following Hematopoietic Stem Cell Transplantation

This Phase I dose-escalation trial is designed to evaluate the safety of rapidly generated multivirus-specific T-cell products with antiviral activity against CMV, EBV, adenovirus, HHV6, BK virus, JC virus, and human parainfluenza-3 (HPIV3), derived from eligible HSCT donors. In this trial, we will utilize a rapid generation protocol for broad spectrum multivirus-specific T cells for infusion to recipients of allogeneic hematopoietic stem cell transplant (HSCT), who are at risk of developing EBV, CMV, adenovirus, HHV6, BKV, JCV and/or HPIV3, or with PCR/culture confirmed active infection(s) of EBV, CMV, adenovirus, HHV6, BKV, JCV, and/or HPIV3 that has failed to resolve with at least 14 days of standard antiviral therapy (if available and tolerated). These cells will be derived from HSCT donors, and the study agent will be assessed at each dose for evidence of dose-limiting toxicities (DLT). This study will have two arms: Arm A will include patients who receive prophylactic treatment, and Arm B will include patients who receive VSTs for one or more active infections with targeted viruses. Determination of the study arm will be determined by the patient's clinical status. Study arms will each be analyzed for safety endpoints and secondary endpoints.

Early Discontinuation of Antibiotic Therapy in Elderly Patients Hospitalized for a Viral Infection

Among winter respiratory viruses, influenza is the most common and therefore responsible for the highest mortality, but parainfluenza and RSV viruses have an even higher risk of mortality (1.6 to 1.9 times), this toll being paid mainly by the elderly and co-morbid population. Futhermore, SARS-Cov2 will probably become endemic and/or epidemic with the same targets of fragile patients. These viral infections are serious, however a bacterial co-infection worsens the prognosis even more: excess risk of mortality = 2.6, 95% CI \[1.9-3.7\]. Although rare, these co-infections are the subject of a prescription of antibiotics in more than 50% of influenza infections or other serious viral infections. Mainly due to this excess risk of mortality associated with the difficulty of diagnosing these co-infections. Proper antibiotic use requires preventing this misuse and its harmful consequences in the short and long term at all costs. It is therefore imperative to have solid (grade A) evidence showing that antibiotic therapy in viral infections is not only futile but also potentially harmful.

Respiratory Infections in Young Children

The goal of this observational study is to learn about the causes, severity, and long-term effects of respiratory tract infections (RTIs) in young children from birth to five years of age in Colombia and Panamá. The main questions it aims to answer are: How often do respiratory infections occur in children under two years old, and which viruses or bacteria cause them? Why do some children develop more severe infections than others? Do early infections or vaccinations change how the immune system responds to future illnesses? How do viruses and bacteria interact in the respiratory tract to influence disease severity and long-term respiratory health? Researchers will follow newborns from birth until age five to understand how respiratory infections develop and affect children's health over time. Participants will not receive any experimental treatment. Families who join the study will: Be contacted twice a week through a phone app or phone calls to check for symptoms of respiratory infection. Attend in-person visits if their child becomes ill and every six months for routine follow-up. Provide nasal and blood samples during illness episodes so researchers can identify the viruses or bacteria causing infection and study how the immune system responds. This study began in May 2024 and is being conducted in Cali, Colombia, and Panamá City, Panamá. The research team plans to continue to include participants and continue active follow-up until the children reach five years of age. The information collected will help scientists and health professionals understand how different pathogens cause respiratory infections, what factors increase the risk of severe illness, and how early infections may influence long-term lung health. The study's findings will support future efforts to prevent and treat respiratory diseases in young children.

The AcCREDiT 2 Study

The ACCREDIT study - Acute respiratory infections and chronic respiratory disease exacerbations characterisation and personalised treatment platform study 2 (AcCREDiT 2). Patients with respiratory infections (such as pneumonia) or exacerbations of chronic respiratory conditions (such as emphysema) often require hospital admission. Infections or exacerbation are commonly caused by bacteria, viruses or fungi. In at least a quarter of patients no infectious cause of the exacerbation is found. Depending on the cause of the respiratory infections or exacerbations of chronic respiratory condition patients require prompt treatment with anti-infective drugs (antibiotics, anti-fungal or antiviral drugs) or anti-inflammatory drugs such as corticosteroids. Patients with respiratory infection or exacerbations of chronic respiratory conditions develop symptoms such as cough, sometimes with sputum, fever or breathlessness. These symptoms can be similar across several conditions, many of which are not due to infection (for example heart failure or blood clots in the lungs). When assessing patients with respiratory symptoms, clinicians face the challenge of limited information in the early stages of care as it takes three days to identify infectious organisms in the laboratory. Even when an infection is strongly suspected, distinguishing bacterial from viral or fungal infections on clinical grounds alone is difficult. This uncertainty often leads clinicians to prescribe a number of treatments, including antibiotics, before a clear diagnosis is made. Timely treatment is crucial for success and improved patient outcomes, especially for critically ill patients admitted to the intensive care unit (ICU). However, antibiotics may cause side effects, such as sickness and diarrhoea, and overuse of antibiotics leads to antibiotic resistance, making antibiotics less effective when they are really needed. Giving antibiotics to patients with an infection or exacerbation and avoiding antibiotics in patients without an infection requires rapid diagnostic tests. Furthermore, giving antibiotics prior to taking samples to diagnose infection can affect the sample being tested making it more likely to not give a useful result. For a diagnostic test for infection to be most useful it needs to be collected before an antibiotic is given - this is true for both clinical tests and those research tests which are clinical tests in development. Modern technologies allow testing for an infection in hours rather than days. In order to understand how effective these technologies are, samples need to be taken from patients before they start treatment. In routine NHS care samples to test for infection should be taken before treatment has been started. However, in research studies samples are often taken up to a day after treatment has started which affects how effective the test is at finding infection. The forerunner to this study, called AcCREDiT, proposed investigating very rapid ways of identifying individuals with respiratory infection and exacerbation. However, the study team encountered challenges during the informed consent process, particularly with acutely unwell patients. Therefore, the AcCREDiT-2 was designed in collaboration with patients and public contributors to look at the feasibility of a modified informed consent process: verbal consent, assent for individuals with capacity to consent for themselves, and deferred consent. AcCREDiT-2 will be an observational study, meaning that no treatment will be changed, and no experimental drugs or tests used to influence the clinical care of participants. AcCREDiT-2 will also be a 'feasibility study', which is a smaller study designed to see what works well before embarking on a larger project. During the study the investigators will collect clinical information and samples, such as blood, sputum and stool, from patients who come to hospital with a presumed respiratory infection or exacerbation of their chronic respiratory condition. The investigators will compare new diagnostic tests to traditional laboratory tests to understand their relative advantages and disadvantages for patient care. This is a 'feasibility' study, a small study ran first to make sure things work properly before expanding to a much larger study.

Profiling Vulnerability and Resilience for Mental Illness Following Viral Infections

This observational study aims to identify the underlying neurobiological and environmental mechanisms that influence vulnerability or resilience to mental illness in the context of infection and their contribution to severe infective outcomes in people with pre-existing mental illness. The main questions it aims to answer are: * How do viral infections influence the development of mental illness? * What neurobiological and environmental factors contribute to influence the development of mental illness following infection? * How do these factors relate to the severity of infectious illness in people with pre-existing mental disorders? Researchers will move from large population databases to well-defined, deeply characterised samples to explore the association between infection and subsequent mental health outcomes, and the biological mechanisms behind these changes. Participants's data has already been collected.

Emergency PWAS in Respiratory Infectious Disease

Develop an emergency PanorOmics Wide Association Study (ePWAS) for the early, rapid biological and pathophysiological characterisation of known and novel Infectious Diseases in adult patients presenting to emergency departments with suspected, acute, community-acquired respiratory infectious disease (scaRID). Phase 1 1. Develop an ED-ID biobank (named ePWAS-RID). Phase 2 2. Targeted research for the discovery of novel diagnostics, prognostics and therapeutics