Background: While the high burden of illness caused by seasonal influenza in children and the elderly is well-recognized, less is known about the burden in adults 50-64 years of age. The lack of data for this age group is a key challenge in evaluating the cost-effectiveness of vaccination programs. We aimed to assess influenza-associated hospitalization and mortality rates, and case fatality rates for hospitalized cases among adults aged 50-64 years. Methods: This review was conducted according to the PRISMA: we searched MEDLINE, EMBASE, Cochrane, Web of Science, and grey literature for articles and reports published since 2010. Studies reporting rates of hospitalization and/or mortality associated with laboratory-confirmed influenza among adults 50-64 or 45-64 years of age for the 2010-11 through 2019-20 seasons were included. Results: Twenty studies from 13 countries were included. Reported hospitalization rates associated with laboratory-confirmed influenza 5.7 to 112.8 per 100,000. Rates tended to be higher in 2015-2019 compared to 2010-2014, and were higher in studies reporting data from high income versus low and middle-income countries. Mortality rates were reported in only one study, with rates ranging from 0.8-3.5 per 100,000 in four different seasons. The case fatality rate among those hospitalized with influenza, as reported by population-based studies, ranged from 1.3% to 5.6%. Conclusions: Seasonal influenza imposes a significant burden of morbidity in adults 50-64 years of age, but with high heterogeneity across seasons and geographic regions. Ongoing surveillance is required to improve estimates of burden to better inform influenza vaccination and other public health policy.

Background: Standard dose seasonal influenza vaccines often produce modest immunogenic responses in adults ≥65 years old. MF59 is intended to elicit a greater magnitude and increased breadth of immune response. Objective: To determine the effectiveness of seasonal MF59-adjuvanted trivalent/quadrivalent influenza vaccine (aTIV/aQIV) relative to no vaccination or vaccination with standard or high dose egg-based influenza vaccines among people ≥65 years old. Methods: Cochrane methodological standards and PRISMA-P guidelines were followed. Real-world evidence from non-interventional studies published in peer reviewed journals and grey literature from 1997 through to July 15, 2020, including cluster-randomized trials, were eligible. Two reviewers independently extracted data and risk of bias was assessed using the ROBINS-I tool. Results: Twenty-one studies conducted during the 2006/07-2019/20 influenza seasons were included in the qualitative review; 16 in the meta-analyses. Meta-analysis of test-negative studies found that aTIV reduced medical encounters due to lab-confirmed influenza with pooled estimates of 40.7% (95% CI: 21.9, 54.9; I2=0%) for general practitioner visits and 58.5% (40.7, 70.9; I2=52.9%) for hospitalized patients. The pooled estimate of VE from case-control studies was 51.3% (39.1, 61.1; I2=0%) against influenza- or pneumonia-related hospitalization. The pooled estimates for the relative VE of aTIV for the prevention of influenza related medical encounters were 13.9% (4.2, 23.5; I2=95.9%) compared with TIV, 13.7% (3.1, 24.2; I2=98.8%) compared with QIV, and 2.8% (-2.9, 8.5; I2=94.5%) compared with HD TIV. Conclusions: Among adults ≥65 years aTIV demonstrated significant absolute VE, improved relative VE compared to non-adjuvanted standard-dose TIV/QIV, and comparable relative VE to high-dose TIV.