SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity

Area of Science:

• Virology
• Genetics
• Immunology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits frequent intra-host evolution within infected individuals.
• Understanding the interplay between viral diversity and disease severity is crucial for managing infections.

Purpose of the Study:

• To investigate the level and pattern of intra-host viral diversity in SARS-CoV-2.
• To analyze the drivers of nucleotide changes, including mutational signatures and immune selection.
• To associate viral diversity with disease severity and host immune factors.

Main Methods:

• Deep sequencing was employed to enumerate intra-host single-nucleotide variants (iSNVs).
• Human leukocyte antigen (HLA) genotyping was performed using Sanger sequencing.
• Medical records were collected and reviewed to assess disease severity.

Main Results:

• A total of 836 iSNVs were identified, exhibiting highly individualized patterns.
• iSNV accumulation correlated with infection duration, peaking early and declining later.
• Specific mutational biases (C>U/G>A and U>C/A>G) were observed, increasing with disease severity.
• Eight iSNVs in the receptor-binding domain showed potential for immune escape.
• Eighteen iSNVs were significantly associated with specific HLA alleles.

Conclusions:

• The level and pattern of iSNVs reflect in vivo viral-host interactions.
• Intra-host viral diversity is linked to SARS-CoV-2 pathogenesis and disease severity.
• Immune selection and mutational processes shape viral evolution during infection.