High Clinical Burden of Influenza Disease in Adults Aged ≥ 65 Years: Can We Do Better? A Systematic Literature Review

Introduction Influenza is a respiratory infection associated with a significant clinical burden globally.

Adults aged ≥ 65 years are at increased risk of severe influenza-related symptoms and complications due to chronic comorbidity and immunosenescence.

Annual influenza vaccination is recommended; however, current influenza vaccines confer suboptimal protection, in part due to antigen mismatch and poor durability.

This systematic literature review characterizes the global clinical burden of seasonal influenza among adults aged ≥ 65 years.

Methods An electronic database search was conducted and supplemented with a conference abstract search.

Included studies described clinical outcomes in the ≥ 65 years population across several global regions and were published in English between January 1, 2012 and February 9, 2022.

Results Ninety-nine publications were included (accounting for > 156,198,287 total participants globally).

Clinical burden was evident across regions, with most studies conducted in the USA and Europe.

Risk of influenza-associated hospitalization increased with age, particularly in those aged ≥ 65 years living in long-term care facilities, with underlying comorbidities, and infected with A(H3N2) strains.

Seasons dominated by circulating A(H3N2) strains saw increased risk of influenza-associated hospitalization, intensive care unit admission, and mortality within the ≥ 65 years population.

Seasonal differences in clinical burden were linked to differences in circulating strains.

Conclusions Influenza exerts a considerable burden on adults aged ≥ 65 years and healthcare systems, with high incidence of hospitalization and mortality.

Substantial influenza-associated clinical burden persists despite increasing vaccination coverage among adults aged ≥ 65 years across regions included in this review, which suggests limited effectiveness of currently available seasonal influenza vaccines.

To reduce influenza-associated clinical burden, influenza vaccine effectiveness must be improved.

Next generation vaccine production using mRNA technology has demonstrated high effectiveness against another respiratory virus—SARS-CoV-2—and may overcome the practical limitations associated with traditional influenza vaccine production.