Molecular and seroepidemiology of SARS-CoV-2 among influenza-like illness and severe Acute respiratory illness cases in selected health facilities in Ethiopia

Abstract

Background: SARS-CoV-2 remains globally circulating, yet post-pandemic comprehensive molecular, serological, and population-level immunity data from low-resource settings such as Ethiopia are limited. This study employed genomic surveillance with seroepidemiological assessment to characterize the epidemiology of SARS-CoV-2 among individuals presenting with influenza-like illness (ILI) and severe acute respiratory infection (SARI) between May 2023 and April 2024 across 21 influenza sentinel surveillance sites representing diverse regions of Ethiopia. Methods: Respiratory swabs from 8,881 ILI/SARI patients were tested for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR). Whole-genome sequencing was performed on samples with cycle threshold (Ct) values ≤ 30 using Oxford Nanopore Technology, and serological testing was performed on blood samples collected from participants aged ≥12 years using the WANTAI enzyme-linked immunosorbent assay (ELISA) targeting the spike receptor-binding domain (RBD). Results: Among 8,881 participants, the overall SARS-CoV-2 detection rate was 3.3 (95% CI: 2.9–3.6). Compared to children under 2 years, older age groups had significantly higher odds of infection: 15–49 years (AOR: 1.60; 95% CI: 1.16–2.21), 50–64 years (AOR: 2.15; 95% CI: 1.31–3.54), and ≥65 years (AOR: 2.37; 95% CI: 1.42–3.95). ILI cases demonstrated higher positivity than SARI cases (AOR: 2.26; 95% CI: 1.75–2.91). SARS-CoV-2 was detected across all seasons, with positivity rates ranging from 1.9% in spring to 6.0% in summer. Whole-genome sequencing of (n = 80) revealed exclusive circulation of Omicron lineages, identifying 19 Omicron sub-lineages, predominantly JN.1.18 (31.3%), JN.1 (8.8%), XBB.1.28 (8.8%), BA.2.86 (7.5%), and XBB.1.34.1 (6.3%). Serological analysis of 690 samples demonstrated 96.8% (95% CI: 95.2–98.0%) seropositivity, with no significant demographic variation. Conclusions: This study demonstrates the continued circulation of SARS-CoV-2 in Ethiopia, primarily among adults with influenza-like illness, with distinct seasonal peaks during the summer. The Omicron variant remained dominant, with JN.1 and its descendants prevailing since late 2023 in parallel with a national rise in COVID-19 cases. These findings reinforce that ongoing genomic and syndromic surveillance utilizing established ILI/SARI platforms remain vital for monitoring viral evolution and guiding targeted public health interventions in low-resource settings.