Evidence of SARS-CoV-2 convergent evolution in immunosuppressed patients treated with antiviral therapies

• Published in: Virology journal 2024-05, Vol.21 (1), p.105-105, Article 105
• Main Authors: Feng, Shuchen, Reid, Gail E, Clark, Nina M, Harrington, Amanda, Uprichard, Susan L, Baker, Susan C
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Neutralizing - immunology; Antiviral agents; Antiviral Agents - therapeutic use; Biological diversity; Care and treatment; Comparative analysis; Convergence (Biology); Convergent evolution; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - virology; COVID-19 Drug Treatment; Dosage and administration; Drug therapy; Evolution, Molecular; Female; Genetic Variation; Genomics; Health aspects; Hospital patients; Humans; Immunocompromised Host; Immunosuppressed patients; iSNVs; Male; Middle Aged; Monoclonal antibodies; Monoclonal antibody treatment; Mutation; Phylogeny; RNA; RNA, Viral - genetics; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; SARS-CoV-2 evolution; Severe acute respiratory syndrome; Viral genetics; Virus research
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-024-02378-y

The factors contributing to the accelerated convergent evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not fully understood. Unraveling the contribution of viral replication in immunocompromised patients is important for the early detection of novel mutations and developing approaches to limit COVID-19. We deep sequenced SARS-CoV-2 RNA from 192 patients (64% hospitalized, 39% immunosuppressed) and compared the viral genetic diversity within the patient groups of different immunity and hospitalization status. Serial sampling of 14 patients was evaluated for viral evolution in response to antiviral treatments. We identified hospitalized and immunosuppressed patients with significantly higher levels of viral genetic diversity and variability. Further evaluation of serial samples revealed accumulated mutations associated with escape from neutralizing antibodies in a subset of the immunosuppressed patients treated with antiviral therapies. Interestingly, the accumulated viral mutations that arose in this early Omicron wave, which were not common in the patient viral lineages, represent convergent mutations that are prevalent in the later Omicron sublineages, including the XBB, BA.2.86.1 and its descendent JN sublineages. Our results illustrate the importance of identifying convergent mutations generated during antiviral therapy in immunosuppressed patients, as they may contribute to the future evolutionary landscape of SARS-CoV-2. Our study also provides evidence of a correlation between SARS-CoV-2 convergent mutations and specific antiviral treatments. Evaluating high-confidence genomes from distinct waves in the pandemic with detailed patient metadata allows for discerning of convergent mutations that contribute to the ongoing evolution of SARS-CoV-2.