Intra-Host Evolution Provides for the Continuous Emergence of SARS-CoV-2 Variants

Area of Science:

• Virology
• Genomics
• Epidemiology

Background:

• Variants of concern (VOC) in SARS-CoV-2 are defined by genomic differences and potential for increased transmissibility or severity.
• The frequency and circumstances of new viral variant emergence remain poorly understood.
• VOC pose a significant threat to public health interventions and vaccination campaigns.

Purpose of the Study:

• To investigate the extent of SARS-CoV-2 sequence evolution within patients.
• To estimate the frequency of emergence for highly diverse viral variants.
• To identify patient groups that may benefit from enhanced sequencing surveillance.

Main Methods:

• Analyzed SARS-CoV-2 genomic sequences from 94 patients.
• Monitored viral evolution over short time periods (2-3 weeks).
• Estimated the frequency of multi-mutation variant emergence in hospitalized cases.

Main Results:

• Two patients developed ≥9 single-nucleotide variants (SNVs) in 2 weeks; one developed 23 SNVs in 3 weeks, including spike protein mutations (D138H, E554D, D614G).
• No significant intra-host evolution was observed in other patients.
• Estimated that up to 2% of hospitalized COVID-19 cases may develop multi-mutation variants within one month of persistent replication.

Conclusions:

• Multi-mutation SARS-CoV-2 variants can emerge locally within one month, even in patients without apparent immune deficiency.
• Persistent intra-host replication facilitates the emergence of diverse viral strains.
• Targeted sequencing surveillance in viremic, reinfection-suspected, and immunocompromised patients is beneficial for public health.