# Distinct Cytokine Landscapes Induced by Influenza a Virus, RSV, and SARS-CoV-2 in Older Adults (65+) Using an Ex Vivo Whole Blood Stimulation Model

## TL;DR

This study compares immune responses in older adults to three respiratory viruses using a blood model and finds distinct patterns of cytokine expression.

## Contribution

The study introduces a novel ex vivo model to compare immune activation profiles in older adults against three viruses.

## Key findings

- RSV stimulation led to higher inflammatory mediator expression compared to other viruses.
- IAV and SARS-CoV-2 induced greater Type I interferon expression.
- SARS-CoV-2 uniquely increased regulatory cytokine expression.

## Abstract

Exaggerated immune responses to respiratory viruses may contribute to increased morbidity in older adults. To investigate virus-specific immune activation in this population, we developed an ex vivo whole blood stimulation model using samples from 30 healthy individuals aged ≥65 years. Whole blood was stimulated with UV-inactivated influenza A virus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2, and the expression of 22 immune-related genes was assessed by quantitative RT-PCR array. All three viruses elicited responses with marked variability across individuals, as well as differences in the magnitude and distribution of cytokine expression across stimuli. RSV stimulation was associated with relatively higher expression of inflammatory mediators, while IAV and SARS-CoV-2 induced greater expression of Type I interferon. SARS-CoV-2 also led to an increased expression of regulatory cytokines. Although individual responses varied, correlation analysis indicated coordinated gene expression within functional categories, and Uniform Manifold Approximation and Projection (UMAP) showed distinct grouping of cytokine responses by virus and function. These findings describe differential immune mRNA expression profiles in response to viral stimuli in older adults and may support future studies aimed at understanding age-related differences in host–virus interactions.