Global distribution and evolution of human metapneumovirus A2b2 clade: Insights from genomic surveillance

Abstract Human metapneumovirus (HMPV), which belongs to the a family, has shown the emergence of the A2b2 clade as the dominant global genotype. Whether this represents true evolutionary selection or surveillance artefacts remains unclear. We analysed 315 complete HMPV genome sequences (1994–2024) from the Nextstrain database using sampling-corrected statistical approaches, including temporal homogeneity testing, rarefaction analysis, and entropy-based dynamics to examine non-random patterns in A2b2 emergence. Temporal homogeneity testing revealed strong directional evolution towards A2b2 dominance ( Z = −46.62, p < 0.001), confirming non-random patterns rather than surveillance artefacts. The clade showed strong persistence (206 self-transitions) with limited backward transitions. After controlling for sampling bias, A2b2 represented 68.3% (95% CI: 58.2–78.4) of isolates in 2023–2024. A2b2 demonstrated significantly higher temporal entropy (2.1) than other clades (A1: 1.2, A2a: 1.5, A2b1: 2.0), indicating more complex dynamics. Geographic rarefaction revealed significant regional structuring, with Africa showing the highest diversity (3.00, 95% CI: 1.00–3.05) despite lower sampling. HMPV A2b2’s global expansion represents genuine directional evolution with potential selective advantages, similar to patterns in respiratory syncytial virus. These findings underscore the need for enhanced genomic surveillance and integration of HMPV monitoring into respiratory virus surveillance frameworks to track emerging variants and assess public health implications.