The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution result in the emergence and persistence of at least three genetically distinct genotypes suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.

Fuente: Cell Reports Medicine
Available online 27 January 2023, 100943