BackgroundIn adults aged 50 + years, vaccine-preventable diseases (VPDs) pose a significant health burden and can lead to additional ‘downstream effects’ of infection beyond the acute phase e.g., increasing the risk for non-communicable disease and exacerbating chronic conditions. The aim was to understand and quantify the burden of VPD downstream effects in hospitalised adults in the United States.MethodsThis retrospective observational study analysed hospitalisation claims data (2016–2019) with 1-year follow-up, in adults with a VPD diagnosis versus matched controls (using Optum’s de-identified Clinformatics Data Mart Database). Outcomes included mortality; increase in Charlson Comorbidity Index (CCI) score; new diagnosis of comorbidities; and loss of independence (defined by need for home health/home care and/or move to long-term facility).ResultsMortality was significantly increased in VPD cases versus controls at 30-day (risk ratio [RR] of 4.08 [95% CI 3.98–4.18]) and 1-year follow-up (RR 2.76 [2.73–2.80]). Over a 1-year follow-up period, morbidity increased following VPD hospitalisation: 65–86% of VPD cases had new comorbidities diagnosed (versus 13–41% of controls); with a significantly higher mean increase in CCI score versus baseline (3.23 in VPD cases versus 0.89 in controls, p < 0.001). Adults were observed to experience a worsening of their health status and were less likely to return to their original health state. In addition, 41% of VPD cases had a loss of independence following hospitalisation versus 12% of controls; as seen by an increased need for home assistance (in 25% versus 9% of controls) and/or a move to a long-term care facility (in 29% versus 6% of controls).ConclusionsThis analysis suggests that VPD hospitalised cases suffer significantly worse clinical outcomes than controls, with downstream effects that include increased mortality and morbidity, and greater loss of independence. Evidence on potential downstream effects of infection is relatively new, and this additional burden is generally not considered in vaccine decision-making. More research is needed to disentangle the effect of VPDs on new comorbidities versus the natural course of the condition. Increasing awareness among adults, healthcare providers and decision makers could help to increase adult vaccination coverage, and reduce the clinical burden of VPDs.