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. 2025 May 23;25(1):738.
doi: 10.1186/s12879-025-11107-x.

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

Abebe M Aga  1 , Demise Mulugeta  2 , Atsbeha Gebreegziabxier  3 , Girum Taye Zeleke  3 , Aderajew Mekonnen Girmay  3 , Gutema Bulti Tura  3 , Abaysew Ayele  2 , Ahmed Mohammed  3 , Tigist Belete  3 , Tefera Taddele  3 , Rajiha Abubeker  3 , Fanos Tadesse Woldemariyam  3 , Tesfaye Gelanew  2 , Yeweynshet Tesera  2 , Bedasa Gidisa  2 , Jaleta Bulti Tura  3 , Gemechu Tadesse Leta  3 , Abraham Ali  3 , Senait Alemayehu Beshah  3 , Bedasa Wagari Likasa  3 , Jemal Mohammed  2 , Dereje Nigussie  2
Affiliations

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

Abebe M Aga et al. BMC Infect Dis. .

Abstract

Background: Extensive vaccination campaigns against COVID-19 have played a significant role in controlling virus spread and preventing severe illness. This study focused on breakthrough infections in vaccinated individuals, raising concerns about vaccine effectiveness against SARS-CoV-2 variant immune escape, with particular attention to lineage distribution among vaccinated and unvaccinated individuals.

Methods: A case-control study was conducted from January to April 2023, sequencing 298 samples from participants who tested positive for COVID-19 via rapid diagnostic test (RDT) from 22 health facilities, including vaccinated and unvaccinated cases. Besides clinical and epidemiological data, nasopharyngeal swabs were obtained, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to determine Cycle threshold (Ct) values, followed by whole genome sequencing of 298 samples fulfilling sequencing criteria to identify variants of concern and specific virus lineages.

Results: Out of 298 samples sequenced, 281 fulfill quality for analysis with 44.8% (126) had received at least one COVID-19 vaccine dose, while 51.9% (146) were not vaccinated, and 3.2% (9) patients had no vaccination records. The analysis showed that all cases were of the Omicron variant, with the XBB.1.5 lineage being the most prevalent (38.4%), followed by FL.2 (9.3%) and XBB.1.9.1.2 (7.8%). The remaining 44.5% comprised a combination of 22 other lineages. The XBB.1.5 variant accounted for 51 (47.2%) cases among vaccinated individuals with at least one dose and 57 (52.8%) among unvaccinated, showing relatively similar prevalence across both groups. The viral load as indicated by the Ct value varied widely, with a significant appearance in the lower ranges (high viral load), suggesting active viral replication. Notably, 25% of samples exhibited high viral loads (Ct values 13-15), showing the high transmissibility of the XBB.1.5 lineage among both vaccinated and unvaccinated populations.

Conclusion: The findings emphasize the need for continuous genomic surveillance and regular vaccine updates to address emerging SARS-CoV-2 variants, particularly the immune-evasive XBB lineage. The high prevalence of variants like XBB.1.5 in breakthrough infection underscores the importance of adaptive vaccination strategies and next-generation vaccines to maintain efficacy. Ongoing monitoring of variant dynamics is crucial for informed public health responses, strengthening pandemic preparedness and future outbreak prevention.

Keywords: Breakthrough infection; Genomic diversity; Lineage; SARS-COV-2 variant; Vaccination.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by Ethiopian Public Health Institute Institutional Review Board (EPHI_IRB) Approval No. 415_2022. All participants have provided informed consent, and data collectors have made it clear that participation is entirely voluntary and the study was conducted in accordance with Declaration of Helsinki. Participants retain the right to withdraw from the study at any time without affecting their access to healthcare services. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests

Figures

Fig. 1
Fig. 1
Phylogenetic relationships and Nextstrain clade assignments of SARS-CoV-2 Omicron variant lineages and sub-lineages detected in Addis Ababa in 2023
Fig. 2
Fig. 2
Lineage distribution by sex
Fig. 3
Fig. 3
Cycle threshold value in association with lineages
See this image and copyright information in PMC

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