Identification and Clinical Validation of Biomarkers Associated With Clinical Severity in Adults Infected With RSV (ARF-RSV)

Identification and Clinical Validation of Biomarkers Associated With Clinical Severity in Adults Infected With Respiratory Syncytial Virus

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.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Other: Nasopharyngeal swabs and biological collection

• Study Type: Observational
• Enrollment (Estimated): 133

Contacts and Locations

• Study Contact: Name: Nicolas de Prost, MD, PhD; Phone Number: (+33) 1 49 81 23 94; Email: nicolas.de-prost@aphp.fr
• Study Contact Backup: Name: Slim Fourati, MD, PhD; Phone Number: (+33) 1 45 17 81 45; Email: slim.fourati@aphp.fr

Study Locations

• France
  • Créteil, France, 94010
    • Recruiting
    • Intensive Care Unit Henri Mondor APHP
    • Contact: Nicolas DE PROST, MD-PHD; Email: nicolas.de-prost@aphp.fr
    • Contact: PIERRE BAY, MD; Email: pierre.bay@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
100 patients with RSV diagnosis; Patients with acute respiratory infection and positive nasopharyngeal PCR or other respiratory specimen for RSV.	Other: Nasopharyngeal swabs and biological collection; Nasopharyngeal PCR; Blood and virological samples taken as part of the research will be included in a biological collection
33 control patients; Patient admitted for acute respiratory syndrome with no diagnosis of respiratory infection or immunosuppression.	Other: Nasopharyngeal swabs and biological collection; Nasopharyngeal PCR; Blood and virological samples taken as part of the research will be included in a biological collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	within 72h of hospitalization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	during hospitalization (until day 28).
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).	during hospitalization (until day 28)
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).	during hospitalization (within 72h of hospitalization)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Pierre-André Natella, PhD, APHP URC

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 26, 2023
• First Submitted That Met QC Criteria: December 26, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: December 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: RSV; Respiratory infection; Respiratory Syncytial Virus; Febrile acute respiratory syndrome; Immuno-virological determinants
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: APHP221290

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No