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A number of vaccines against Respiratory Syncytial Virus (RSV) infection are approaching licensure. Deciding which RSV vaccine strategy, if any, to introduce, will partly depend on cost-effectiveness analyses, which compares the relative costs and health benefits of a potential vaccination programme. Health benefits are usually measured in Quality Adjusted Life Year (QALY) loss, however, there are no QALY loss estimates for RSV that have been determined using standardised instruments. Moreover, in children under the age of five years in whom severe RSV episodes predominantly occur, there are no appropriate standardised instruments to estimate QALY loss. We estimated the QALY loss due to RSV across all ages by developing a novel regression model which predicts the QALY loss without the use of standardised instruments. To do this, we conducted a surveillance study which targeted confirmed episodes in children under the age of five years (confirmed cases) and their household members who experienced symptoms of RSV during the same time (suspected cases.) All participants were asked to complete questions regarding their health during the infection, with the suspected cases aged 5-14 and 15+ years old additionally providing Health-Related Quality of Life (HR-QoL) loss estimates through completing EQ-5D-3L-Y and EQ-5D-3L instruments respectively. The questionnaire responses from the suspected cases were used to calibrate the regression model. The calibrated regression model then used other questionnaire responses to predict the HR-QoL loss without the use of EQ-5D instruments. The age-specific QALY loss was then calculated by multiplying the HR-QoL loss on the worst day predicted from the regression model, with estimates for the duration of infection from the questionnaires and a scaling factoring for disease severity. Our regression model for predicting HR-QoL loss estimates that for the worst day of infection, suspected RSV cases in persons five years and older who do and do not seek healthcare have an HR-QoL loss of 0.616 (95% CI 0.155-1.371) and 0.405 (95% CI 0.111-1.137) respectively. This leads to a QALY loss per RSV episode of 1.950 × 10-3 (95% CI 0.185 × 10-3 -9.578 × 10-3 ) and 1.543 × 10-3 (95% CI 0.136 × 10-3 -6.406 × 10-3 ) respectively. For confirmed cases in a child under the age of five years who sought healthcare, our model predicted a HR-QoL loss on the worst day of infection of 0.820 (95% CI 0.222-1.450) resulting in a QALY loss per RSV episode of 3.823 × 10-3 (95% CI 0.492 × 10-3 -12.766 × 10-3 ). Combing these results with previous estimates of RSV burden in the UK, we estimate the annual QALY loss of healthcare seeking RSV episodes as 1,199 for individuals aged five years and over and 1,441 for individuals under five years old. The QALY loss due to an RSV episode is less than the QALY loss due to an Influenza episode. These results have important implications for potential RSV vaccination programmes, which has so far focused on preventing infections in infants-where the highest reported disease burden lies. Future potential RSV vaccination programmes should also evaluate their impact on older children and adults, where there is a substantial but unsurveilled QALY loss. Funding: National Institute for Health Research, the Medical Research Council, EU Horizon 2020 I-MOVE+, NIHR CLAHRC North Thames.

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