Abstract
BACKGROUND: While rhinoviruses (RVs) typically cause mild respiratory infections, their persistence during the SARS-CoV-2 pandemic, particularly in Hong Kong's strict zero-coronavirus disease 2019 policy, revealed unexpected epidemiological patterns. Two distinct RV surges emerged despite stringent public health measures, suggesting unique transmission advantages among circulating strains. We hypothesised that RV persistence during pandemic restrictions reflected strain-specific adaptations in respiratory tract replication efficiency and/or immune evasion. METHODS: We analysed RV genotypes and conducted blinded clinical severity assessment for 96 paediatric hospitalisations during 2020-2021 outbreaks, compared with 180 age- and sex-matched control subjects from the corresponding weeks in pre-pandemic years (2018-2019). RV isolates from 2020 to 2021 outbreaks were characterised for their replication competence and transcriptomic responses in primary human nasal epithelial cell (HNEC) and environmental stability assays, using RV-A16 and RV-A1B as controls. RESULT: Minor group genotypes RV-A47 and RV-A49 were overrepresented during these two outbreaks. RV-A49 exhibited comparable replication efficiency to RV-A16 but induced significantly stronger transcriptomic responses, notably enhanced TNF and IL-1 signalling, in HNECs, alongside robust replication competence. Our data also suggests the association of RV-A49 with tachypnoea in 2021, particularly in younger males, though limited by a small sample size and single-centre design. CONCLUSION: The predominance of RV-A49 in hospitalised children during the SARS-CoV-2 pandemic potentially driven by its replication competence in HNECs and its capacity to enhanced inflammatory responses. The result is hypothesis-generating, warranting further studies with historical strains and broader populations to confirm strain-specific severity.