Expression Patterns of Interferons and Proinflammatory Cytokines in the Upper Respiratory Tract of Patients Infected by Different Viral Pathogens: Correlation with Age and Viral Load

Respiratory tract infections are a major cause of morbidity and mortality. After the SARS-CoV-2 pandemic, pathogenetic mechanisms leading to more severe outcomes were investigated, including uncontrolled viral replication in the upper airways. This was only partially investigated for other respiratory viruses. We measured mucosal expression of IFN-β1, IFN-λ1, IFN-λ2/3, IL-1β, and IL-6 in patients infected by human metapneumovirus, human rhinovirus, human respiratory syncytial virus or type A influenza virus. A total of 806 nasopharyngeal swabs were collected from patients presenting at emergency departments or hospitalized. Viral load was inferred through cycle threshold determination, whereas cytokine levels were measured through mRNA detection. Each expression pattern was correlated with age, viral load, and specific infecting virus. IFN-β1 and IFN-λ2/3 showed a negative correlation with viral load, while IFN-λ1 and IL-6 exhibited the opposite trend, suggesting increased inflammation with higher viral load. This was more evident in the ≥70-year-old group, with significantly higher IL-6 levels. Higher viral load of potentially more pathogenic viruses was associated with higher IL-6 expression. Cytokine production in the upper respiratory tract is only partially influenced by age per se, with a more relevant role played by viral load and specific infecting virus. In older patients, this response is less coordinated and prone to elicit a proinflammatory response, especially when clinically impacting viruses are involved.