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Accelerated Sars-Cov-2 Intrahost Evolution Leading To Distinct Genotypes During Chronic Infection, Chrispin Chaguza, Anne M. Hahn, Mary E. Petrone, Shuntai Zhou, David Ferguson, Mallery I. Breban, Kien Pham, Mario A. Peña-Hernández, Christopher Castaldi, Verity Hill, Yale Sars-Cov-2 Genomic Surveillance Initiative, Wade Schulz, Ronald I. Swanstrom, Scott C. Roberts, Nathan D. Grubaugh, Kendall Billig, Rebecca Earnest, Joseph R. Fauver, Chaney C. Kalinch, Nicholas Kerantzas, Tobias R. Koch, Bony De Kumar, Marie L. Landry, Isabel M. Ott, David Peaper, Irina R. Tikhonova, Chantal B. F. Vogels

Journal Articles: Epidemiology

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (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 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting …