Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection
Chrispin Chaguza1, Anne M Hahn1, Mary E Petrone1,2
1Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
Medrxiv : the Preprint Server for Health Sciences
|July 7, 2022
Summary
Untreated chronic SARS-CoV-2 infections accelerate virus evolution, increasing the risk of novel variant emergence. This study tracked genetic diversity during a 471-day infection, revealing rapid viral mutation rates.
Area of Science:
- Virology
- Evolutionary Biology
- Infectious Diseases
Background:
- The emergence of novel SARS-CoV-2 variants like Omicron supports the chronic infection hypothesis.
- Investigating intrahost evolution during prolonged SARS-CoV-2 infection is crucial for understanding variant emergence.
Approach:
- Analyzed intrahost evolution and genetic diversity of SARS-CoV-2 lineage B.1.517 during a 471-day chronic infection.
- Utilized unique molecular indexes for accurate intrahost viral sequencing to track genetic diversity dynamics.
- Quantified the virus evolutionary rate and identified advantageous mutations.
Key Points:
- Chronic infection exhibited an accelerated virus evolutionary rate (35 nucleotide substitutions/year), approximately double the global rate.
- At least three genetically distinct SARS-CoV-2 genotypes emerged and persisted within the host.
- Spatially structured viral populations were suggested, with continuous reseeding of genotypes into the nasopharynx.
Conclusions:
- Untreated chronic SARS-CoV-2 infections significantly accelerate viral evolution.
- Chronic infections provide opportunities for the emergence of genetically divergent and potentially more transmissible variants.
- Understanding intrahost evolution is key to predicting and mitigating the impact of future SARS-CoV-2 variants.
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