Comparison of human metapneumovirus and respiratory syncytial virus-associated health burden in adults living with chronic underlying health conditions: a systematic review and meta-analysis

Background: We aimed to systematically compare the health burden associated with hMPV and RSV respiratory tract infections in adults with chronic illnesses. Methods: We searched MEDLINE, EMBASE, Global Health, CINAHL, Web of Science, and Global Index Medicus on 18/08/2025 and 12/01/2026. We included observational and interventional studies conducted from 2001 onwards, reporting laboratory-confirmed hMPV and RSV infections in adults with chronic illnesses. Quality assessment was conducted using the Joanna Briggs Institute critical appraisal tools. We developed an overall estimate, using a generalised linear mixed-effects model with a binomial distribution and logit link, including a study-level random intercept and fixed effects for virus, setting, and their interaction. Predicted probabilities and population-average odds ratios (OR) comparing RSV and hMPV were calculated. Incidence and disease severity outcomes were synthesised narratively due to heterogeneous and limited data. The protocol was registered on Open Science Framework [doi:10.17605/OSF.IO/EPB3X]. Results: Fifty studies were included, reporting on hMPV and RSV test positivity (n=44; 29,603 laboratory tests), incidence (n=3), and disease severity outcomes (n=7). The OR of RSV test positivity versus hMPV in adults with at least one chronic illness was 1.88 (95% CI: 1.61–2.19) in inpatient settings and 1.65 (1.43–1.91) across all settings in studies relying on annual data. Significant differences in RSV versus hMPV test positivity were found for chronic respiratory disease (annual and seasonal analyses), cardiovascular (seasonal), immunocompromised (annual), and haematologic (annual) conditions, but not among solid organ transplant recipients (annual). Incidence and severity data demonstrated inconsistent patterns. Conclusions: RSV occurs more frequently than hMPV in adults living with chronic illnesses. However, evidence gaps remain regarding comparative disease severity and data from low- and middle-income countries. Funding: AstraZeneca plc.