Respiratory viruses: improving molecular diagnostic tools and assessment of clinical impact in lung transplant recipients

Respiratory viruses are the most frequent cause of infections in humans and can promote seriouscomplications in immunocompromised subjects or those with chronic lung diseases. In lung transplantrecipients, the graft itself is directly exposed to these viruses and thus particularly at risk of dysfunctiononce infected. In previous studies, we have described the impact of these viruses in hospitalizedsubjects and identified unexpected complications in lung transplant recipients. These observationsand a recent pilot study have established the basis of the present multidisciplinary collaborationbetween the University Hospitals of Geneva and Lausanne. The goal is to carefully assess symptomsassociated with viral infections and to evaluate whether respiratory viruses can trigger acute rejectionand bronchiolitis obliterans, the main cause of progressive graft dysfunction and death. To achievethis goal, we will use a longitudinal clinical follow-up approach by enrolling all transplant recipients inour network together with a systematic viral screening over four winter seasons. In order to avoid anyselection bias, we have planned prescheduled screening periods that will be conducted in all cohortsubjects three times per year independent of any symptoms or clinical conditions present. In addition,subjects will be screened systematically during the first three months following transplantation andduring each acute respiratory event and bronchoalveolar lavage procedure. The virological screeningwill use an updated panel of RT-PCR assays applied systematically on upper respiratory specimensand bronchoalveolar lavage fluids when available. The diagnostic assays will be redesignedspecifically for the present project using our most recent expertise and an extensive sequencecollection. The goal here is to design assays likely to detect any divergent strains or new viral variants.This project will provide not only the epidemiological pattern of respiratory viral infections, but also adescription of the associated symptoms and lung function abnormalities. In addition, the study isdesigned to specifically assess the potential causal link between viral respiratory infections and acuteor chronic graft rejections. Another major objective will be to analyze the potential pathologicalabnormalities or specific patterns linked to viral respiratory tract infections. In summary, we willaddress the very relevant question of the short- and long-term impact of these viral infections whichhas never been studied so extensively so far. Our position at the interface between molecular virologyand clinical sciences offers the unique opportunity to correlate clinical end-points with solid virologicalfindings. We have benefited from a preliminary funding that has not only allowed us to establish thebasis of this project, but also to launch the investigation. This strategy potentiates and synergizes thepresent funding request. Keywords transplantation; viral infections; graft rejection; Rhinovirus; Respiratory virus; Lung transplant recipients; Tanzania; Cycstic Fibrosis Hauptdisziplin Innere Medizin