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

NCT07643688 | Not Yet Recruiting

• 1 other identifier: AIRE-INT
• Study Type: observational
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

SARS CoV 2 Infection; RSV Infections; Influenza Infection

Keywords

SARS-CoV-2; Influenza, Human; Respiratory Syncytial Viruses; Observational Study; Programmed Cell Death 1 Receptor; Primary Health Care; Kinetics

Outcome Measures

Primary Outcomes (1)

• Expression of PD-L1

  Quantification of PD-L1 expression in peripheral blood and evaluation of changes in expression between the acute phase (24-72 hours after symptom onset) and the early recovery phase (5-9 days after symptom onset) in ambulatory older adults with respiratory infection.

  Visit 1 (24-72 hours after symptom onset) and Visit 2 (5-9 days after symptom onset).

Study Arms (2)

Positive for RSV, Infuenza, SARS-CoV-2

Negative for RSV, Infuenza, SARS-CoV-2

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

People aged 60 years or older who attended the healthcare service with flu-like symptoms.

You may qualify if:

• GROUP A (Infected-Positive)
• Age ≥60 years.
• Symptoms compatible with viral respiratory infection (fever, cough, nasal congestion, dyspnea, etc.) between 24h and 72h from symptom onset.
• Confirmed diagnosis, positive for influenza, RSV, or SARS-CoV-2 by rapid test.
• Signed informed consent at visit 1.
• GROUP B (Non-Infected-Negative. Controls)
• Age ≥60 years.
• Negative diagnosis for influenza, RSV, or SARS-CoV-2 by rapid test.
• Signed informed consent at visit 1.

You may not qualify if:

• Known severe immunosuppression (e.g., transplant recipient, uncontrolled HIV).
• Chronic immunosuppressive treatment (except low-dose corticosteroids (≤10 mg/3 months)).
• Participation in another clinical trial within the last 30 days.
• Inability to comply with the visit schedule.
• Immunosuppressive drugs.
• Drugs indicated for treatment.
• Oncology patients.
• Terminal patients.
• Autoimmune diseases associated with alterations in PD-L1.
• Systemic lupus erythematosus (SLE).
• Rheumatoid arthritis (RA).
• Multiple sclerosis (MS).
• Type 1 diabetes mellitus (T1DM).
• Sjögren's syndrome.
• Myasthenia gravis.

Sponsors & Collaborators

• Fabiana Sherine Ganem dos Santos: lead
• Fundació Institut Germans Trias i Pujol: collaborator
• Germans Trias i Pujol Hospital: collaborator
• AFFIRMA BIOTECH: collaborator
• Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina: collaborator

Related Publications (9)

• Surie D, Self WH, Zhu Y, Yuengling KA, Johnson CA, Grijalva CG, Dawood FS; Investigating Respiratory Viruses in the Acutely Ill (IVY) Network. RSV Vaccine Effectiveness Against Hospitalization Among US Adults 60 Years and Older. JAMA. 2024 Oct 1;332(13):1105-1107. doi: 10.1001/jama.2024.15775.

  PMID: 39230920 BACKGROUND

• Payne AB, Watts JA, Mitchell PK, Dascomb K, Irving SA, Klein NP, Grannis SJ, Ong TC, Ball SW, DeSilva MB, Natarajan K, Sheffield T, Bride D, Arndorfer J, Naleway AL, Koppolu P, Fireman B, Zerbo O, Timbol J, Goddard K, Dixon BE, Fadel WF, Rogerson C, Allen KS, Rao S, Mayer D, Barron M, Reese SE, Rowley EAK, Najdowski M, Ciesla AA, Mak J, Reeves EL, Akinsete OO, McEvoy CE, Essien IJ, Tenforde MW, Fleming-Dutra KE, Link-Gelles R. Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis. Lancet. 2024 Oct 19;404(10462):1547-1559. doi: 10.1016/S0140-6736(24)01738-0.

  PMID: 39426837 BACKGROUND

• Zhang P, Wang Y, Miao Q, Chen Y. The therapeutic potential of PD-1/PD-L1 pathway on immune-related diseases: Based on the innate and adaptive immune components. Biomed Pharmacother. 2023 Nov;167:115569. doi: 10.1016/j.biopha.2023.115569. Epub 2023 Sep 26.

  PMID: 37769390 BACKGROUND

• Valero-Pacheco N, Arriaga-Pizano L, Ferat-Osorio E, Mora-Velandia LM, Pastelin-Palacios R, Villasis-Keever MA, Alpuche-Aranda C, Sanchez-Torres LE, Isibasi A, Bonifaz L, Lopez-Macias C. PD-L1 expression induced by the 2009 pandemic influenza A(H1N1) virus impairs the human T cell response. Clin Dev Immunol. 2013;2013:989673. doi: 10.1155/2013/989673. Epub 2013 Sep 26.

  PMID: 24187568 BACKGROUND

• Influenza vaccination rates https://www.oecd.org/en/data/indicators/influenza-vaccination-rates.html

  BACKGROUND

• CDC Seasonal Flu Vaccine Effectiveness Studies | Flu Vaccines Work https://www.cdc.gov/flu-vaccines-work/php/effectiveness-studies/index.html accesed access September 25, 2025

  BACKGROUND

• CDC Seasonal Flu Vaccine Effectiveness Studies | Flu Vaccines Work https://www.cdc.gov/flu-vaccines-work/php/effectiveness-studies/index.html, accesed access September 25, 2025

  BACKGROUND

• Krammer F, Palese P. Advances in the development of influenza virus vaccines. Nat Rev Drug Discov. 2015 Mar;14(3):167-82. doi: 10.1038/nrd4529.

  PMID: 25722244 BACKGROUND

• Celik I, Saatci E, Eyuboglu AF. Emerging and reemerging respiratory viral infections up to Covid-19. Turk J Med Sci. 2020 Apr 21;50(SI-1):557-562. doi: 10.3906/sag-2004-126.

  PMID: 32293833 BACKGROUND

MeSH Terms

Conditions

COVID-19; Respiratory Syncytial Virus Infections; Influenza, Human

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Orthomyxoviridae Infections

Study Officials

• Concepcio Violan Fors, MD, PhD

  IDIAP JGOL- Unitat de Suport a la Recerca Metropolitana Nord

  PRINCIPAL INVESTIGATOR

• Pere Joan Cardona, MD, PhD

  Instituto Germans Trias i Pujol - IGTP

  STUDY DIRECTOR

Central Study Contacts

Concepcio Violan Fors, MD, PhD

CONTACT

0034607072592; cviolanf.mn.ics@gencat.cat

Fabiana Ganem, MPH, PhD

CONTACT

fganem@idiapjgol.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 60 Days
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Co-Investigator

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: June 11, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share