A short description, 5000 characters Intro: Respiratory Syncytial Virus (RSV) is a frequent, ubiquitous agent of respiratory viral infections. It is the leading viral cause of lower respiratory tract infection (LRTI) in infants and also causes significant morbidity and mortality in adults, especially in the elderly, in patients with cardiorespiratory comorbidities \[e.g., patients with Chronic Obstructive Pulmonary Disease (COPD) and/or heart failure\], and in immunocompromised patients. Clinical phenotyping of RSV respiratory infections has shown that the occurrence of LRTI in RSV-infected patients is associated with the need for ventilatory support and an increased risk of mortality. Virological data also suggest that there is a relationship between high nasopharyngeal viral replication levels and a poor prognosis, although these data have not been confirmed in other studies. Beyond viral load, the impact of viral subtypes on the severity of RSV infection is controversial. Few data have explored the prognostic value of genetic diversity (i.e., role of RSV variants, mutations occurring during clinical course) in RSV-infected adult patients with acute respiratory failure.
Objective: The main goal of the present study is to identify and validate biomarkers associated with RSV severity in adults infected with RSV that will be useful to guide treatment decisions in the future. This study will additionally characterize the thus far unknown genetic diversity of RSV in hospitalized adults with severe and mild infections, in order to anticipate virological escape mechanisms from current and future treatments.
Method: This is a prospective multicenter cohort study of patients with RSV infection admitted to the hospital. These patients will be followed-up for 28 days. Nasopharyngeal samples will be obtained sequentially (i.e., at day 0, day 3-4, day 5-7, and day 14 of inclusion) for virological and transcriptomic analyses. Blood samples will also be collected at day 0 (EDTA tubes and Paxgene tubes) for peripheral transcriptomic analyses and plasma banking.
The 100 first patients included in the study will be allocated to the development cohort and the last 100 patients will be allocated to the validation cohort.
Age > 18 years
Positive RSV RT-PCR in nasopharyngeal swab
Patient admitted to the hospital (intensive care unit or medical ward admission at inclusion) with clinical signs of lower respiratory tract infection (defined as the presence of two or more respiratory signes (cough, dyspnea, sputum production, wheezing, tachypnea (respiratory rate>20/min) or one respiratory sign plus one or more systemic symptoms (fatigue and fever)) requiring hospitalization.
No objection letter (from the patient or a member of family if the patient is not physically able to give consent
Co-infection with other respiratory viruses
Persons under guardianship/guardianship
AME (state medical aid) patient
Age>18 years
Patients with RSV diagnosis : Patients hospitalized for RSV respiratory infection requiring hospital admission. Control group : patients admitted for acute respiratory failure free for RSV or any other infection.
Cohort
Prospective
Nasopharyngeal swabs and biological collection
Other intervention* Nasopharyngeal PCR * Blood and virological samples taken as part of the research will be included in a biological collection
Inflammatory and immune response
Patients with severe disease, defined as developing acute respiratory failure with a World Health Organization (WHO) ten-point scale ≥6 at any time of hospital stay, and those with mild disease (WHO ten-point scale remaining \<6 during hospital stay) will be compared using several biological tools, in particular the inflammatory and immune response assessed by transcriptomic analyses in peripheral blood and in respiratory samples (nasopharyngeal swabs and bronchoalveolar lavage fluid or tracheal aspirates when available).
Inflammatory and immune response during hospital stay
Differences between the two groups of RSV-infected patients, with severe disease (WHO ten-point scale ≥6) versus mild disease (WHO ten-point scale remaining \<6), of inflammatory and immune responses assessed by transcriptomic analyses in respiratory samples (nasopharyngeal swabs and bronchoalveolar lavage fluid or tracheal aspirates when available).
RSV genetic variability during hospitalization
Relationship between viral level dynamics and intra-individual viral genetic variability in respiratory samples (nasopharyngeal swabs and bronchoalveolar lavage fluid or tracheal aspirates when available).
RSV genetic variability at admission
Differences between the two groups of RSV-infected patients, with severe disease (WHO ten-point scale ≥6) versus mild disease (WHO ten-point scale remaining \<6), of inter-individual viral genetic variability in respiratory samples (nasopharyngeal swabs).
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