Multiple Introductions of Mpox virus to Ireland during the 2022 International Outbreak

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Abstract Background mpox (formerly Monkeypox) virus (MPXV) was considered a rare zoonotic disease prior to May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Previously, mpox infection was associated with symptoms similar to smallpox, although substantially less severe, including fever, an extensive characteristic rash and swollen lymph nodes. Aim Elucidating the origin and molecular characteristics of the virus circulating in the Republic of Ireland in the period between May and November 2022. Methods Whole-genome sequencing of all MPXV cases (80%; n=178/219) analysed against sequences from public databases (n=2695). Bayesian approaches were used to infer the divergence time between sequences from different subclades and transmission events involving different countries. Results The circulating virus belonged to the clade IIb B.1 lineage and, notably, the presence of twelve separable and highly-supported subclades consistent with multiple introductions into the country. Such a hypothesis of multiple importation events was supported further by the estimation of the time to the divergence of subclades. Additionally, inferred MPXV transmissions involving different countries and continents were indicative of an extended international spread. The analysis of the mutations in the Irish sequences revealed 93% of the mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across the subclades. Conclusion In the context of extremely high national sequencing coverage, we provide new insights into the international origin and transmission dynamics supporting multiple introductions into the Republic of Ireland. Conflict of Interests None to declare.

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