The XEC Variant: Genomic Evolution, Immune Evasion, and Public Health Implications

Abstract

Narrative review synthesizes the most current literature on the SARS-CoV-2 XEC variant, focusing on its genomic evolution, immune evasion characteristics, epidemiological dynamics, and public health implications. To achieve this, we conducted a structured search of the literature of peer-reviewed articles, preprints, and official surveillance data from 2023 to early 2025, prioritizing virological, clinical, and immunological reports related to XEC and its parent lineages. Defined by the distinctive spike protein mutations, T22N and Q493E, XEC exhibits modest reductions in neutralization in vitro, although current evidence suggests that mRNA booster vaccines, including those targeting JN.1 and KP.2, retain cross-protective efficacy against symptomatic and severe disease. The XEC strain of SARS-CoV-2 has drawn particular attention due to its increasing prevalence in multiple regions and its potential to displace other Omicron subvariants, although direct evidence of enhanced replicative fitness is currently lacking. Preliminary analyses also indicated that glycosylation changes at the N-terminal domain enhance infectivity and immunological evasion, which is expected to underpin the increasing prevalence of XEC. The XEC variant, while still emerging, is marked by a unique recombination pattern and a set of spike protein mutations (T22N and Q493E) that collectively demonstrate increased immune evasion potential and epidemiological expansion across Europe and North America. Current evidence does not conclusively associate XEC with greater disease severity, although additional research is required to determine its clinical relevance. Key knowledge gaps include the precise role of recombination events in XEC evolution and the duration of cross-protective T-cell responses. New research priorities include genomic surveillance in undersampled regions, updated vaccine formulations against novel spike epitopes, and long-term longitudinal studies to monitor post-acute sequelae. These efforts can be augmented by computational modeling and the One Health approach, which combines human and veterinary sciences. Recent computational findings (GISAID, 2024) point to the potential of XEC for further mutations in under-surveilled reservoirs, enhancing containment challenges and risks. Addressing the potential risks associated with the XEC variant is expected to benefit from interdisciplinary coordination, particularly in regions where genomic surveillance indicates a measurable increase in prevalence.

Keywords: Omicron sublineage; SARS-CoV-2; XEC variant; immune evasion; pandemic preparedness; vaccine efficacy.

Figure 1

Weekly global prevalence of SARS-CoV-2 variants XEC and KP.3.1.1 from Epiweek 34 to Epiweek 47 of 2024. Stacked area chart displaying the relative weekly proportions of GISAID-submitted sequences identified as XEC (blue) and KP.3.1.1 (red) at eight surveillance time points. Data were derived from the WHO variant tracking summaries using GISAID aggregate reports between 19 August and 7 December 2024. XEC prevalence rose steadily from 2.0% in Epiweek 34 to 36.8% by Epiweek 47, while KP.3.1.1 initially increased to 48.8% in Epiweek 44 before gradually declining to 41.8%. Data was generated from [17,33,38,39].