Genome diversity of SARS-CoV-2 lineages associated with vaccination breakthrough infections in Addis Ababa, Ethiopia

Introduction COVID 19 vaccination have played a pivotal role in reducing the severity and spread of the disease. Breakthrough infections among vaccinated individuals have raised concerns about vaccine effectiveness due to emerging variants capable of immune escape. This study investigates genome diversity of SARS-CoV-2 in Ethiopia, focusing on lineage distribution among vaccinated and unvaccinated individuals to understand transmission dynamics and implications for public health interventions. Methods A case control study was conducted from January to April 2023 across 22 health facilities. Nasopharyngeal swabs were collected from 298 individuals who tested positive for COVID 19 using rapid diagnostic tests (RDTs). Reverse transcription quantitative PCR (RT qPCR) was performed to determine viral load based on Cycle threshold (Ct) values. Whole genome sequencing was conducted to identify SARS-CoV-2 lineages associated with breakthrough infections in vaccinated individuals compared to unvaccinated cases. Results Of the 298 samples sequenced, 281 passed quality thresholds for genomic analysis. Among these, 44.8% (126) had received at least one vaccine dose, 51.9% (146) were unvaccinated, and 3.2% (9) had unknown vaccination status. All sequences belonged to the Omicron variant, with XBB.1.5 dominant lineage (38.4%), in both vaccinated and unvaccinated cases, followed by FL.2 (9.3%) and XBB.1.9.1.2 (7.8%), The rest of 22 other lineages comprised 44.5% cases. XBB.1.5 was detected in 47.2% of vaccinated and 52.8% of unvaccinated individuals. Notably, 25% of cases exhibited high viral loads (Ct values13–15), suggesting strong viral replication and high transmissibility, even among vaccinated individuals. Conclusion The predominance of the immune evasive XBB.1.5 lineage in both vaccinated and unvaccinated individuals highlights potential continued transmission and breakthrough infections. These emphasize critical need for continuous genomic surveillance, timely vaccine updates, and the development of vaccines for adaptive vaccination strategies and real time monitoring of variant dynamics to maintain vaccine effectiveness and enhance pandemic preparedness effort.