Accelerated SARS-CoV-2 Intrahost Evolution Leading to Distinct Genotypes During Chronic Infection

Authors

Chrispin Chaguza, Yale School of Public Health
Anne M. Hahn, Yale School of Public Health
Mary E. Petrone, Yale School of Public Health
Shuntai Zhou, Yale School of Public Health
David Ferguson, Yale School of Public Health
Mallery I. Breban, Yale School of Public Health
Kien Pham, Yale School of Public Health
Mario A. Peña-Hernández, Yale School of Public Health
Christopher Castaldi, Yale University
Verity Hill, Yale School of Public Health
Yale SARS-CoV-2 Genomic Surveillance Initiative
Wade Schulz, Yale School of Medicine
Ronald I. Swanstrom, University of North Carolina at Chapel Hill
Scott C. Roberts, Yale School of Medicine
Nathan D. Grubaugh, Yale School of Public Health
Kendall Billig, Yale SARS-CoV-2 Genomic Surveillance Initiative
Rebecca Earnest, Yale SARS-CoV-2 Genomic Surveillance Initiative
Joseph R. Fauver, University of Nebraska Medical CenterFollow
Chaney C. Kalinch, Yale SARS-CoV-2 Genomic Surveillance Initiative
Nicholas Kerantzas, Yale SARS-CoV-2 Genomic Surveillance Initiative
Tobias R. Koch, Yale SARS-CoV-2 Genomic Surveillance Initiative
Bony De Kumar, Yale SARS-CoV-2 Genomic Surveillance Initiative
Marie L. Landry, Yale SARS-CoV-2 Genomic Surveillance Initiative
Isabel M. Ott, Yale SARS-CoV-2 Genomic Surveillance Initiative
David Peaper, Yale SARS-CoV-2 Genomic Surveillance Initiative
Irina R. Tikhonova, Yale SARS-CoV-2 Genomic Surveillance Initiative
Chantal B. F. Vogels, Yale SARS-CoV-2 Genomic Surveillance Initiative

Document Type

Article

Journal Title

Cell Reports Medicine

Publication Date

2023

Volume

4

Abstract

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 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.

MeSH Headings

Humans, SARS-CoV-2, COVID-19, Persistent Infection, Genome, Viral, Genotype

DOI Link

10.1016/j.xcrm.2023.100943

ISSN

2666-3791

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Chaguza, Chrispin; Hahn, Anne M.; Petrone, Mary E.; Zhou, Shuntai; Ferguson, David; Breban, Mallery I.; Pham, Kien; Peña-Hernández, Mario A.; Castaldi, Christopher; Hill, Verity; Yale SARS-CoV-2 Genomic Surveillance Initiative; Schulz, Wade; Swanstrom, Ronald I.; Roberts, Scott C.; Grubaugh, Nathan D.; Billig, Kendall; Earnest, Rebecca; Fauver, Joseph R.; Kalinch, Chaney C.; Kerantzas, Nicholas; Koch, Tobias R.; De Kumar, Bony; Landry, Marie L.; Ott, Isabel M.; Peaper, David; Tikhonova, Irina R.; and Vogels, Chantal B. F., "Accelerated SARS-CoV-2 Intrahost Evolution Leading to Distinct Genotypes During Chronic Infection" (2023). Journal Articles: Epidemiology. 182.
https://digitalcommons.unmc.edu/coph_epidem_articles/182