Understanding the Global Burden of Influenza in Adults Aged 18-64 years: A Systematic Literature Review from 2012 to 2022.

INTRODUCTION: Adults aged 18-64 years comprise most of the working population, meaning that influenza infection can be disruptive, causing prolonged absence from the workplace, and reduced productivity and the ability to care for dependents. Influenza vaccine uptake is relatively low, even among the older adults in this population (i.e., aged 50-64 years), reflecting a lack of perceived need for vaccination. This systematic literature review (SLR) aimed to characterize the global burden of influenza in the 18-64 years population. METHODS: An electronic database search was conducted and supplemented with conference and gray literature searches. Eligible studies described at least one of clinical, humanistic, or economic outcomes in adults aged 18-64 years and conducted across several global regions. Included studies were published in English, between January 1, 2012, and September 20, 2022. RESULTS: A total of 40 publications were included, with clinical, humanistic, and economic outcomes reported in 39, 5, and 15, respectively. Risk of influenza-associated clinical outcomes were reported to increase with age among the 18-64 years population, including hospitalizations (Yamana et al. in Intern Med 60:3401-3408, 2021; Derqui et al. in Influenza Other Respir Viruses 16:862-872, 2022; Fuller et al. in Influenza Other Respir Viruses 16:265-275, 2022; Ortiz et al. in Crit Care Med 42:2325-2332, 2014; Yandrapalli et al. in Ann Transl Med 6:318, 2018; Zimmerman et al. in Influenza Other Respir Viruses 16:1133-1140, 2022). ICU admissions, mortality, ER/outpatient visits, and use of mechanical ventilation were recorded. Adults aged 18-64 years with underlying comorbidities were at higher risk of influenza-related hospitalizations, ICU admission, and mortality than otherwise healthy individuals. Length of hospital stay increased with age, although a lack of stratification across other economic outcomes prevented identification of further trends across age groups. CONCLUSIONS: High levels of hospitalization and outpatient visits demonstrated a clinical influenza-associated burden on patients and healthcare systems, which is exacerbated by comorbidities. Considering the size and breadth of the general population aged 18-64 years, the limited humanistic and economic findings of this SLR likely reflect an underreported burden. Greater investigation into indirect costs and prolonged absenteeism associated with influenza infection is required to fully understand the economic burden in this population.