# Molecular Epidemiology of SARS-CoV-2 in Northern Greece from the Index Case up to Early 2025 Using Nanopore Sequencing

## TL;DR

This study tracks the genetic evolution of SARS-CoV-2 in northern Greece from early 2020 to 2025, highlighting the spread of key variants and the importance of genomic surveillance.

## Contribution

The study provides a five-year genomic analysis of SARS-CoV-2 in northern Greece, including detailed lineage tracking and insights into recombination events.

## Key findings

- Early introductions included B.1, B.1.177, and B.1.258 lineages.
- Omicron variants BA.4/BA.5 and JN.1 became dominant in 2022 and 2024, respectively.
- Recombinants XDK, XDD, and XEC were identified and tracked using PANGO nomenclature.

## Abstract

Background/Objectives: Since its emergence in late 2019, SARS-CoV-2 has demonstrated remarkable genetic diversity driven by mutations and recombination events that shaped the course of the COVID-19 pandemic. Continuous genomic monitoring is essential to track viral evolution, assess the spread of variants of concern (VOCs), and inform public health strategies. The present study aimed to characterize the molecular epidemiology of SARS-CoV-2 in northern Greece from the first national case in February 2020 through early 2025. Methods: A total of 66 respiratory samples collected from hospitalized patients across Northern Greece were subjected to whole-genome sequencing using Oxford Nanopore Technologies’ MinION Mk1C platform and the ARTIC protocol. Sequences were analyzed with PANGO, Nextclade, and GISAID nomenclature systems for lineage and clade assignment, and the WHO nomenclature for VOCs. Results: Across 66 genomes, 34 PANGO lineages were identified. Early introductions included B.1 (2/66), B.1.177 (3/66), and B.1.258 (1/66). Alpha (5/66) and Beta (5/66) circulated in February–June 2021. Delta (AY.43) was detected in early 2022 (2/66; Jan–Feb) but was rapidly displaced by Omicron and reached 100% of the sequences by May 2022. Omicron diversified into BA.1/BA.1.1 (3/66), BA.2 (6/66), BA.4/BA.5 (14/66), BF.5 (1/66), EG.5 (1/66; designated a WHO Variant of Interest in 2023), JN.1 (4/66; globally dominant lineage prompting vaccine updates in 2024–2025), KS.1 (2/66; together with KS.1.1 are recognized PANGO lineages that were tracked internationally but remained less prevalent), KP.3 (5/66; together with KP.3.1.1, prominent “FLiRT” descendants circulating in 2024), and recombinants XDK, XDD, and XEC (5/66), reported by their PANGO names in accordance with the WHO’s current framework, which reserves Greek letters only for newly designated VOCs. Conclusions: This five-year genomic analysis provides an insight into the continuous evolution of SARS-CoV-2 in northern Greece. The findings underscore the importance of sustained genomic surveillance, integrated with epidemiological data, to detect emerging variants, monitor recombination, and strengthen preparedness for future coronavirus threats.