2026/01/19 by Carol Moraga, Francisco Francisco Kirhman, Barbara Bernal +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #SARS-CoV-2 and COVID-19 Research #SARS-CoV-2 detection and testing #vaccines and immunoinformatics approaches
paper · pdf · doi:10.64898/2026.01.15.699801
openalex publication_date 2026/01/19 · openalex created_date 2026/01/21 · openalex updated_date 2026/07/14
As COVID-19 enters an endemic phase, SARS-CoV-2 continues to diversify under ongoing immune pressure, with Omicron sublineages and episodic emergent variants sustaining reinfections worldwide. Intra-host evolution represents the earliest stage of this diversification, yet remains undercharacterized, particularly in regions with limited genomic surveillance. Here, we conducted high-throughput sequencing on 96 nasopharyngeal swab samples from Chilean individuals (2020-2022), achieving an average per-base genome coverage of ~60,000x across the viral genome. This ultra-deep sequencing coverage enabled the identification of intra-host single-nucleotide variants (iSNVs) and co-infection events with high sensitivity and accuracy. Co-infections, especially with Omicron, significantly increased iSNV frequency and recombination, driving viral diversity. Evolutionary analysis based on the non-synonymous to synonymous ratio (dN/dS) shows that Omicron is under extensive purifying selection (global dN/dS ~ 0.55). However, Omicron co-infection cases exhibited higher dN/dS ratios (~0.58), suggesting a lower level of purifying selection and increased genetic diversity. Notably, the Spike gene showed dN/dS ratios indicative of positive selection (dN/dS > 1), which are more pronounced in co-infection cases than in Omicron alone. This suggests that co-infections are providing the substrate for the emergence of new variants with enhanced transmissibility and immune evasion capabilities. Together, these findings demonstrate that ultra-deep sequencing is crucial for mapping the evolutionary forces driving SARS-CoV-2 intra-host adaptation and the emergence of new variants.