Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection

Yale SARS-CoV-2 Genomic Surveillance Initiative

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Article number100943
JournalCell Reports Medicine
Issue number2
StatePublished - Feb 21 2023


  • COVID-19 vaccines
  • SARS-CoV-2
  • chronic infection
  • epidemiology
  • genomic surveillance
  • immunocompromised individual
  • intrahost evolution
  • intrahost genotypes
  • mutation dynamics
  • variant emergence

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


Dive into the research topics of 'Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection'. Together they form a unique fingerprint.

Cite this