Clinical trial NCT06197152: Identification and Clinical Validation of Biomarkers Associated With Clinical Severity in Adults Infected With RSV
Official title: Identification and Clinical Validation of Biomarkers Associated With Clinical Severity in Adults Infected With Respiratory Syncytial Virus
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory Syncytial Virus
RSV
Respiratory infection
Febrile acute respiratory syndrome
Immuno-virological determinants
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-01-09
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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.


Eligibility criteria: Group of patients with RSV diagnosis

Inclusion Criteria:

* 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

Exclusion Criteria:

* Co-infection with other respiratory viruses
* Persons under guardianship/guardianship
* AME (state medical aid) patient

Group of "control" patients

Inclusion Criteria :

* Age\>18 years
* Patient's consent
* Enrolled in a social security plan
* Admitted for an acute respiratory syndrome
* No diagnosis of respiratory infection in the 4 weeks prior to inclusion
* Negative RSV nasopharyngeal PCR (or other respiratory specimen) collected within the last 48 hours
* No immunosuppression (HIV infection, bone marrow or solid organ transplantation, post-chemotherapy aplasia, immunosuppressive therapy, corticosteroid therapy (\> 200 mg/d hydrocortisone or equivalent within 4 weeks prior to inclusion)

Exclusion Criteria :

* Persons under guardianship/guardianship
* AME (state medical aid) patient

Primary outcomes:
measure: Inflammatory and immune response
timeFrame: within 72h of hospitalization
Secondary outcomes:
measure: Inflammatory and immune response during hospital stay
timeFrame: during hospitalization (until day 28).
measure: RSV genetic variability during hospitalization
timeFrame: during hospitalization (until day 28)
measure: RSV genetic variability at admission
timeFrame: during hospitalization (within 72h of hospitalization)
Other outcomes:
Locations:
city: Créteil
country: France
facility: Intensive Care Unit Henri Mondor APHP
Study officials:
affiliation: APHP URC
name: Pierre-André Natella, PhD
role: STUDY_CHAIR
References: