Human Respiratory Syncytial Virus Genetic Diversity and Lineage Replacement in Ireland pre- and post-COVID-19 pandemic

Abstract

AbstractBackgroundHuman respiratory syncytial virus (HRSV) is a common cause of lower respiratory tract infections globally. Newly-licensed prophylactic vaccines and monoclonal antibodies are anticipated to alleviate this burden; however, such interventions may exert selective pressures on HRSV evolution.MethodsWhole-genome sequencing was performed on HRSV-A (n=123) and -B (n=110) samples collected during three HRSV seasons in the 2021-2024 period from community cases. Additionally, G gene sequences, HRSV-A (n=141) and -B (n=141), collected in the 2015-2019 period were examined. Lineages were assigned by phylogenetic analyses including reference lineages.ResultsPhylogenetic trees inferred with the G gene and whole genomes were consistent. Changes in the prevalence of certain lineages post-COVID-19 reflected the impact of non-pharmaceutical interventions introduced to reduce SARS-CoV-2 transmission. The HRSV-A lineages A.D.1 and A.D.5 were dominant, while B.D.E.1 was the dominant lineage for HRSV-B. Similar trends were also observed in prevalent lineages in the European region. The emergence of a new lineage was identified as descended from A.D.1 with eight distinctive substitutions in proteins G, F and L. Other circulating lineages with amino acid substitutions were observed in the F glycoprotein which could impact binding sites of nirsevimab.ConclusionWe provide the first comprehensive analysis of HRSV transmission and evolution in Ireland over the last decade through the selective forces created by the measures introduced during the COVID-19 pandemic. This study provides a foundation for future public health surveillance employing pathogen genomics to enable an evidence-based assessment of the impact of pharmaceutical interventions on HRSV evolution and disease severity.Key public health messageWhat did you want to address in this study and why?We aimed to address conditions enabling the yearly increase in the number of HRSV cases in recent years and the viral genetic diversity. A whole-genome sequencing-based molecular epidemiology of HRSV will be key to monitoring the effectiveness and impact of new immunisation programmes in the coming years.What have we learnt from this study?We have established a genomic-epidemiological baseline for HRSV in Ireland, and demonstrated a significant change in the diversity and abundance of viral lineages in circulation before, and after, the early years of the COVID-19 pandemic. Such changes in the most prevalent HRSV genetic lineages were shown to follow a similar trend across Europe during this time.What are the implications of your findings for public health?The characterised viral genetic diversity represents a benchmark for evidence-based future assessments of the effectiveness and the impact of new pharmaceutical interventions in Ireland i.e. monoclonal antibodies and HRSV vaccines for paediatric, geriatric and immunocompromised cohorts. Such preventive options are anticipated to reduce the HRSV burden to public health and better protect the populations at risk.