Clinical Research Directory

Expression of Inflammatory Markers in the Course of Acute Respiratory Viral Infections

Respiratory viral infections caused by influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 remain major causes of morbidity, hospitalization, and mortality among older adults worldwide. Current antiviral therapies have limited effectiveness and generally require administration within the first 48 hours after symptom onset. Increasing evidence suggests that the programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) immune checkpoint pathway plays an important role in the host immune response during acute viral respiratory infections. Upregulation of PD-L1 has been associated with impaired antiviral T-cell activity, immune exhaustion, and disease progression in influenza, RSV, and SARS-CoV-2 infections. The AIRE-INT study is a prospective, observational, multicenter, non-interventional study designed to characterize the temporal kinetics of PD-L1 expression and inflammatory biomarkers in adults aged 60 years or older presenting with acute respiratory viral infection. The study will be conducted in primary care centers and urgent care facilities within the Barcelonès Nord and Maresme healthcare regions in Catalonia, Spain. A total of 150 participants will be enrolled, including 75 with confirmed viral respiratory infection and 75 controls with negative rapid antigen tests for influenza, RSV, and SARS-CoV-2. Eligible participants must be aged ≥60 years and present within 24 to 72 hours after the onset of respiratory symptoms compatible with acute viral infection, including fever, cough, nasal congestion, or dyspnea. Participants in the infected group must have a positive rapid antigen test for influenza, RSV, or SARS-CoV-2. Control participants must test negative for all three viruses. Written informed consent will be obtained before enrollment. Participants with severe immunosuppression, chronic immunosuppressive therapy, active oncologic disease, terminal illness, or autoimmune diseases associated with PD-L1 dysregulation will be excluded. Each participant will be followed for up to 60 days and will complete two in-person study visits and one follow-up assessment. Visit 1 will occur between 24 and 72 hours after symptom onset and will include informed consent, collection of demographic and clinical data, assessment of symptoms and medical history, rapid antigen testing, and blood sample collection for PD-L1 and inflammatory biomarker analyses. Visit 2 will occur between 5 and 9 days after symptom onset and will include repeat clinical assessment and blood sample collection to evaluate temporal changes in PD-L1 expression and inflammatory responses during the acute phase of infection. Visit 3 will occur between 30 and 60 days after symptom onset and will consist of clinical follow-up through telephone contact and electronic medical record review to assess symptom resolution, complications, hospitalization, intensive care admission, and mortality. Laboratory analyses will include flow cytometry quantification of PD-L1 expression and evaluation of inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), complete blood count parameters, renal and hepatic function markers, and virus-specific IgG antibodies. Blood samples will be processed according to standardized laboratory procedures at the Hospital Germans Trias i Pujol Microbiology Department. The primary objective is to characterize the temporal profile of PD-L1 expression from symptom onset to infection resolution in older adults with influenza, RSV, or SARS-CoV-2 infection. Secondary objectives include: Describing the evolution of inflammatory serum biomarkers and their association with disease severity. Identifying biomarkers useful for screening, prognosis, and clinical monitoring. Establishing a biological reference framework for future evaluation of PD-L1 inhibitors in respiratory viral infections. The primary outcome measure is the level and temporal evolution of PD-L1 expression and inflammatory biomarkers between study visits. Secondary outcomes include hospitalization, intensive care admission, mortality at 60 days, symptom duration, and clinical progression. Statistical analyses will include descriptive and univariate analyses, longitudinal modeling of biomarker kinetics using locally estimated scatterplot smoothing (LOESS) and nonlinear mixed-effects regression models, and predictive logistic regression models evaluating associations between biomarkers and clinical outcomes. The study is expected to provide important information regarding the kinetics of PD-L1 expression and inflammatory responses during acute respiratory viral infections in older adults. The findings may support the development of prognostic biomarkers and future host-directed therapeutic strategies targeting the PD-1/PD-L1 pathway across multiple respiratory viruses.

Virological Surveillance of Acute Respiratory Infection in Primary Health Care in Metropolitan France

Every year in the fall and winter, numerous respiratory viruses (such as influenza viruses, SARS-CoV-2 (COVID-19), RSV, rhinovirus, and metapneumovirus) circulate in mainland France, causing acute respiratory infections (ARIs). These viruses can cause epidemics of varying severity, requiring close monitoring to determine their circulation levels and adapt public health measures accordingly. In France, ARI surveillance relies on two networks: the Sentinelles network in primary care and the RENAL network in hospitals. The Sentinelles surveillance is conducted in collaboration with Santé publique France, the National Reference Center for Respiratory Infection Viruses (Institut Pasteur and Hospices Civils de Lyon), and the University of Corsica. As part of the virological surveillance of ARIs, Sentinelles physicians are asked to collect nasopharyngeal swabs or saliva samples from a sample of patients presenting with an ARI during their clinic visits. This surveillance makes it possible to identify respiratory viruses circulating in primary care (general practice and pediatrics), to describe confirmed cases for each of the circulating viruses, and to estimate the impact of each on general practice. This surveillance also allows for the evaluation of the effectiveness of vaccines against influenza and COVID-19.

A Clinical Trial on Safety in Pregnant Women and How Well the Infant is Protected Against RSV-associated Lower Respiratory Tract Infection When the Pregnant Woman Receives the Approved RSV Vaccine Compared to a Placebo.

Respiratory syncytial virus (RSV) is a virus that often affects children during childhood. Even though most cases of RSV are mild, it can cause serious disease and even death - especially in very young babies, babies born too early and those born with heart and lung problems. It is the most common cause for children under 5 years old to be hospitalised. In 2019, there were about 33 million RSV-infections in the lower respiratory tract (in the lungs and below the voice box) of which 3,6 million people were hospitalised and 26,300 passed away in hospital due to RSV. Almost half (50%) of deaths that are caused by RSV, happen in children younger than 6 months old and the majority (more than 95%) of these deaths happen to infants and children in low- and middle-income countries. A way that can help protect babies from becoming infected is through giving vaccines against the germ (RSV) that is targeted for prevention. There are currently no registered vaccines that can be given directly to babies however there is a lot of information available that shows that a vaccine can be safely giving to a mother while she is still pregnant. The mother then produces antibodies (protection cells) that is transferred to the baby before the baby is born, and the baby is protected from getting sick during the first few months of life. One of the vaccines that has been developed (ABRYSVO) has been used in many clinical trials in pregnant moms (and older people) to test if it is safe and will protect young babies and much older people who are all at the highest risk for a severe RSV disease. The vaccine was given to more than 4,000 pregnant women. The results from the study and previous studies showed that the vaccine was safe and the babies had a lower chance of getting severe RSV disease and going to hospital. It showed that the vaccine prevented severe RSV infection in around 80% of babies younger than 90 days, and 70% of babies younger than 6 months. Therefore, the vaccine has been licensed in a few countries around the world (including the United States of America and other high-income countries) which means that pregnant women can receive this vaccine during their pregnancy if they wish to (without being on a clinical trial). It has also been licensed in South Africa but is not yet available in the country for pregnant women to receive. The licensure is also underway in other African countries. However, the results of the previous studies of this vaccine also showed that a slightly higher number of premature babies were born to women who received the vaccine compared to women who did not receive the vaccine. The information received from these studies was however not enough to decide if the earlier births were related to the vaccine or not, and more information is needed - which is one of the main reasons for this study. Importantly, all of the babies who were born earlier were only born a few weeks earlier than expected (around 35 weeks of pregnancy), and all the babies were well and survived. The previous studies on this vaccine happened during the COVID-19 pandemic at which time people were wearing masks and contacting other people less therefore not spreading RSV around as we would normally expect. By doing this study, it will assist the investigators to determine if the vaccine is really as good as it is perceived to be for preventing serious RSV illness in the babies. This RSV vaccine is a very important medical intervention, and it is as important that the effect that this vaccine will have on pregnant women and on the infants born to mothers who receive the vaccine can be measured. It is especially important in African and lower-middle income countries as the vaccine was not tested as much in people living in Africa compared to others. Therefore, the main reason for doing this trial is to see how much value the vaccine can bring to these countries in terms of protecting young babies and infants where many may get a severe infection and be hospitalised. It will also measure if the vaccine does increase the chances of a baby being born earlier than expected. It will only be carried out in the countries after the vaccine has been approved for use by pregnant women (at the right time) as part of their pregnancy care.