Epidemiology and Burden of Human Metapneumovirus Among Italian Adults in Outpatient and Inpatient Settings, 2014--2025

ntroduction: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of acute respiratory infections (ARI) in older adults. However, primary care data on RSV infections are scarce. Methods: We conducted a prospective cohort study over two winter seasons (2022-2023 and 2023-2024) in Italy and the Netherlands (NCT06318936). Older adults (≥ 60 years) presenting to primary care with ARI were tested for RSV and influenza. Clinical and socioeconomic burden was assessed through questionnaires on Days 1, 14, and 30. In secondary analyses, we compared between RSV- and influenza-positive patients and estimated RSV-ARI incidence in Dutch primary care. Results: Of 703 older adults tested, 93 (13.2%) were RSV-positive and 100 (14.2%) influenza-positive. In RSV patients (mean age: 76 years [SD: 8], 63% ≥ 1 comorbidity), mean illness duration was 17 days (SD: 10). Repeat primary care visits occurred in 38% (33/87), emergency department referral in 5% (4/88), and hospitalization in 2% (2/88) of RSV patients. The mean costs per RSV episode were €78.1 (95%CI: 74.4-81.8) and €279.7 (95%CI: 245.5-318.2) from a healthcare system and societal perspective, respectively. The annual RSV-ARI incidence rate was 10.3 episodes per 1000 person-years. RSV patients were significantly older, and had less often fever, muscle pain, and fatigue than influenza patients, but clinical and socioeconomic burdens were comparable. Conclusions: This prospective study is the first sufficiently large to demonstrate that the primary care burden of RSV infections among older adults is substantial and comparable with influenza. These findings are highly relevant for informing public health decisions on novel RSV vaccines.