Human Influenza Virus Infection: A Focus on Key Host Determinants Linked to Clinical Disease Severity

: Influenza viruses remain a major health threat, causing significant illness, death, and high healthcare costs worldwide, despite ongoing research and prevention efforts. A complex interaction between host and viral factors greatly influences the outcomes of influenza infection. Early research mainly focused on the influenza virus's characteristics, but gaining an in-depth understanding of host factors involved in infection helps identify those that may influence disease severity. Notably, as the number of people with one or more comorbidities-that is, conditions that increase the risk of severe influenza-continues to rise, it becomes even more important to investigate the role of host factors. Recognizing host risk factors associated with severe outcomes, mainly caused by excessive inflammatory responses and disruption of epithelial barrier function, is crucial in identifying predictive markers and developing host-based prevention and treatment strategies, especially during pandemics. Moreover, early identification of host risk factors can help reduce severe outcomes and healthcare costs due to hospitalization. To achieve this, detailed analyses of the molecular signature of the host response to influenza virus infection are essential. This review highlights key host factors involved in severe influenza, allowing a better understanding of their roles, especially at the cellular level.