32nd International Dynamics & Evolution of Human Viruses

MUTATIONAL DYNAMICS OF SARS-COV-2 IN PATIENTS WITH PERSISTENT INFECTION

Not scheduled

20m

Abbaye de Royaumont, Asnières-sur-Oise, France

Poster Within-host dynamics & adaptation Virtual posters

Speakers

Alen Suljič (Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana)Ms Anja Ošep (Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana)

Description

Background:
Persistent SARS-CoV-2 infections in immunocompromised individuals are often associated with key features of viral evolution, including accelerated mutation rates, emergence of novel variants of concern (VOCs), cryptic lineages, reservoirs of antiviral resistance, super-spreading events and interspecies transmission. These patients represent a critical group for the understanding of viral evolution. However, the interplay between viral genomic diversity and immune response remains poorly understood and understudied.
Methods:
A total of 629 samples from 82 immunocompromised patients with persistent infections of 40 to 276 days duration were collected and analyzed from the pre-Alpha, Alpha, Delta, and Omicron phases. Consensus sequences and variant data were obtained using next-generation sequencing (ARTIC protocol). A comprehensive analysis of within-host diversity was performed at both the consensus and minor variant levels, focusing on the number, position and context of mutations. Host-associated mutational processes were assessed by mutational signature decomposition.
Results:
The analysis revealed an accelerated mutation rate, particularly in minor level variants. This increase was preceded by a decrease in the ratio of transitions to transversions (Ts/Tv). Mutation dynamics were predominantly driven by non-synonymous substitutions, while indel frequencies remained stable. The ratio of synonymous to non-synonymous substitutions mirrored the Ts/Tv trend, with a marked decrease at the onset of a significant increase in minor level mutations. Mutational signature analysis (SBS-96) emphasized the dominant role of APOBEC family enzymes, followed by ROS and ADAR activity.
Conclusions:
Using advanced analytical approaches, we detected significant shifts in selection pressure and mutagenesis in SARS-CoV-2 infections in immunocompromised patients. These results highlight the intricate dynamics of viral evolution in this population and provide important insights into the conditions that facilitate the emergence of new viral variants.

Keywords: SARS-CoV-2 evolution, persistent infection, viral genomic diversity, variant analysis, mutational signatures