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Updated: Jun 10, 2025

Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
Published on: September 22, 2023
Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2
Majdouline El Moussaoui1, Sebastien Bontems2, Cecile Meex2
1Department of Infectious Diseases and General Internal Medicine, University Hospital of Liège, 1 Avenue de l'Hôpital, Liège 4000, Belgium.
Abstract:
Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of novel lineages. While intrahost evolution of the virus in chronically infected patients has previously been reported, existing knowledge is primarily based on samples from the nasopharynx. In this study, we investigate the intrahost evolution and genetic diversity that accumulated during a prolonged SARS-CoV-2 infection with the Omicron BF.7 sublineage, which is estimated to have persisted for >1 year in an immunosuppressed patient. Based on the sequencing of eight samples collected at six time points, we identified 87 intrahost single-nucleotide variants, 2 indels, and a 362-bp deletion. Our analysis revealed distinct viral genotypes in the nasopharyngeal (NP), endotracheal aspirate, and bronchoalveolar lavage samples. This suggests that NP samples may not offer a comprehensive representation of the overall intrahost viral diversity. Our findings not only demonstrate that the Omicron BF.7 sublineage can further diverge from its already exceptionally mutated state but also highlight that patients chronically infected with SARS-CoV-2 can develop genetically specific viral populations across distinct anatomic compartments. This provides novel insights into the intricate nature of viral diversity and evolution dynamics in persistent infections.
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