Respiratory virus immune response in the aged host

Viruses are a major cause of acute respiratory illness in older adults and pose a substantial burden as the elderly population continues to grow. In the current COVID-19 global health crisis, achieving a better understanding of the aging immune system proves to be an imperative step in preventing and treating respiratory viral infections in older patients. Furthermore, many common respiratory viruses infecting older adults, including human metapneumovirus and parainfluenza virus, do not have licensed vaccines, thereby increasing the risk of severe infection in the aged host. Moreover, given the slowed immune response of older adults, vaccine efficacy for respiratory viruses such as influenza in older adults is minimal, indicating the need to develop more potent vaccines. A better understanding of the aging immune system would allow vaccines to target immunological deficits in the aged host. Three aspects of the aging immune system affect the response to respiratory viruses and vaccines: [1] innate immunity [2], the “inflammaging” hypothesis, and [3] the adaptive immune response. Several innate immune cells (neutrophils, macrophages, dendritic cells, and natural killer cells) as well as adaptive immune cells (T and B lymphocytes) exhibit significant functional impairment in older adults. The inflammaging hypothesis bridges the innate and adaptive arms of the immune system. This review aims to consolidate current knowledge and fill gaps in our understanding of the aged immune response to respiratory viruses.