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

• Published in: Advances in therapy Vol. 40; no. 4; pp. 1601 - 1627
• Main Authors: Langer, Jakob, Welch, Verna L., Moran, Mary M., Cane, Alejandro, Lopez, Santiago M. C., Srivastava, Amit, Enstone, Ashley L., Sears, Amy, Markus, Kristen J., Heuser, Maria, Kewley, Rachel M., Whittle, Isabelle J.
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01-04-2023
• Subjects: Adult; Aged; Cardiology; COVID-19; Endocrinology; Humans; Influenza A Virus, H3N2 Subtype; Influenza Vaccines - therapeutic use; Influenza, Human - epidemiology; Influenza, Human - prevention & control; Internal Medicine; Medicine; Medicine & Public Health; Oncology; Original Research; Pharmacology/Toxicology; Rheumatology; SARS-CoV-2; Vaccination; Mortality; Vaccination; Burden of disease; Hospitalization; Older adults; mRNA vaccine; Strain
• ISSN: 0741-238X; 1865-8652; 1865-8652
• DOI: 10.1007/s12325-023-02432-1

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.