Clinical trial NCT06401720: Age Related Differences in Respiratory Immune Responses in Influenza Virus Infection
Official title: Respiratory Immune Responses in Human Influenza Virus Infection Across Age to Understand What Dictates Disease Severity
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Influenza A Infection
Influenza B Virus Infection
SARS CoV 2 Infection
RSV Infection
Keywords: Influenza A virus (IAV)
Influenza B virus (IBV)
SARS CoV 2
respiratory syncytial virus (RSV)
immunology
age-related differences
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2024-05-07
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients are from primary care clinics, hospitalized, or household contacts of subjects seeking health care at a primary care clinic.

The study population is included in the greater Stockholm area within the Region Stockholm health care region.

Brief summary: The goal of this observational study is to understand immune responses to viral airway infection in adults, including the elderly. The main question(s) to answer is/are:

Why do some individuals acquire only asymptomatic or mild Influenza A virus (IAV) infection while others become severely ill and even succumb to the same disease?

Participants will be asked to donate samples when seeking health care for influenza-like symptoms or if hospitalized for IAV or SARS-CoV-2. Samples asked for are:

* Blood sample by venepuncture
* Blood sample by capillary sampling
* Nasopharyngeal aspirate
* Nasopharyngeal swab
* Endotracheal tube aspirate
* Nasal swab
* Nasal curette
* Breath Explor (sampling of expired air)

Researchers will compare obtained results with the same type of samples from healthy controls.

Detailed description: This observational study will specifically investigate different immunological parameters in blood and at the site of infection in patients with IAV symptoms or confirmed infection to understand parameters related to disease course. Blood and airway samples will be analyzed for immune cell subsets and their functionality, antibodies and other soluble mediators and linked to clinical data. Immune cells will be analyzed using multi-color flow cytometry, RNA sequencing, and in vitro functionality assays. Fluids (plasma, serum, supernatants from airway samples and cell culture supernatants) will be analyzed using ELISA (and or similar methods), proximity extension assay (Olink), etc.

Eligibility criteria: Inclusion Criteria Patients:

* Influenza A like symptoms and/or
* Confirmed airway infection

Exclusion Criteria Patients:

* Current malignancies
* Immunosuppressive treatment, not including/except hydrocortisone

Exclusion Criteria Controls:

* Airway infection within the past four weeks
* Ongoing antibiotic treatment
* Immunosuppressive treatment

Primary outcomes:
measure: Frequency of immune cells
timeFrame: Samples are taken at several different occasions when the patient is experiencing an airway infection and during convalescence. Samples are taken during a time frame of up to 6 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Familjeläkarna
city: Stockholm
country: Sweden
facility: Haga Närakut
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Stockholm
country: Sweden
facility: Sabbatsbergs sjukhus
city: Södertälje
country: Sweden
facility: Södertälje Sjukhus
Study officials:
affiliation: Karolinska Institutet
name: Anna Smed Sörensen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yu M, Charles A, Cagigi A, Christ W, Osterberg B, Falck-Jones S, Azizmohammadi L, Ahlberg E, Falck-Jones R, Svensson J, Nie M, Warnqvist A, Hellgren F, Lenart K, Arcoverde Cerveira R, Ols S, Lindgren G, Lin A, Maecker H, Bell M, Johansson N, Albert J, Sundling C, Czarnewski P, Klingstrom J, Farnert A, Lore K, Smed-Sorensen A. Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19. Nat Commun. 2023 Apr 15;14(1):2164. doi: 10.1038/s41467-023-37835-9.
citation: Vangeti S, Falck-Jones S, Yu M, Osterberg B, Liu S, Asghar M, Sonden K, Paterson C, Whitley P, Albert J, Johansson N, Farnert A, Smed-Sorensen A. Human influenza virus infection elicits distinct patterns of monocyte and dendritic cell mobilization in blood and the nasopharynx. Elife. 2023 Feb 8;12:e77345. doi: 10.7554/eLife.77345.
citation: Cagigi A, Yu M, Osterberg B, Svensson J, Falck-Jones S, Vangeti S, Ahlberg E, Azizmohammadi L, Warnqvist A, Falck-Jones R, Gubisch PC, Odemis M, Ghafoor F, Eisele M, Lenart K, Bell M, Johansson N, Albert J, Salde J, Pettie DD, Murphy MP, Carter L, King NP, Ols S, Normark J, Ahlm C, Forsell MN, Farnert A, Lore K, Smed-Sorensen A. Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination. JCI Insight. 2021 Nov 22;6(22):e151463. doi: 10.1172/jci.insight.151463.
citation: Falck-Jones S, Vangeti S, Yu M, Falck-Jones R, Cagigi A, Badolati I, Osterberg B, Lautenbach MJ, Ahlberg E, Lin A, Lepzien R, Szurgot I, Lenart K, Hellgren F, Maecker H, Salde J, Albert J, Johansson N, Bell M, Lore K, Farnert A, Smed-Sorensen A. Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity. J Clin Invest. 2021 Mar 15;131(6):e144734. doi: 10.1172/JCI144734.