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Published on: June 30, 2023
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Patterns of within-host genetic diversity in SARS-CoV-2
Gerry Tonkin-Hill1, Inigo Martincorena1, Roberto Amato1
1Wellcome Sanger Institute, Hinxton, United Kingdom.
Elife
|August 13, 2021
Summary
Within-host genetic diversity in SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) samples reveals mutation patterns and potential for tracking transmission. However, mutational hotspots and co-infections can complicate accurate reconstruction of transmission chains.
Area of Science:
- Virology
- Genetics
- Epidemiology
Background:
- Monitoring SARS-CoV-2 spread and reconstructing transmission chains is crucial for public health.
- Consensus genome sequences have limitations for detailed transmission chain reconstruction due to SARS-CoV-2's mutation rate and rapid spread.
- Within-host genetic diversity offers a potential avenue for identifying close contacts and refining transmission dynamics.
Purpose of the Study:
- To analyze patterns of within-host genetic diversity in SARS-CoV-2 samples.
- To investigate the mechanisms driving mutation accumulation within hosts.
- To assess the utility and limitations of within-host diversity for reconstructing SARS-CoV-2 transmission chains.
Main Methods:
- High-depth sequencing of 1181 SARS-CoV-2 samples in duplicate.
- Analysis of within-host mutation spectra and allele frequencies.
- Application of an epidemiological inference framework to integrate findings.
Main Results:
- 95.1% of samples exhibited detectable within-host mutations.
- Strand asymmetries in mutational spectra suggest RNA editing or damage, not replication errors, are primary drivers.
- Strong purifying selection was observed against both within- and between-host diversity, especially nonsense mutations.
- Recurrent mutations, potentially indicating mutational hotspots, were identified.
- Multiple instances of co-infection were detected.
- Sharing of within-host variants can aid transmission reconstruction but is confounded by hotspots and superinfections.
Conclusions:
- Within-host genetic diversity provides valuable insights into SARS-CoV-2 mutation dynamics and potential transmission links.
- RNA editing or damage significantly influences SARS-CoV-2 mutation accumulation.
- While useful, within-host variants require careful interpretation due to factors like mutational hotspots and co-infections, which can complicate epidemiological inference.
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