Updated SARS-CoV-2 single nucleotide variants and mortality association

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• Single nucleotide variants (SNVs) in SARS-CoV-2 have evolved rapidly.
• Previous studies analyzed SNVs before June 2020, necessitating updated analysis.

Purpose of the Study:

• To analyze changes in SARS-CoV-2 SNV clustering since June 2020.
• To identify emerging SNV groups and their association with patient demographics and mortality.
• To investigate the structural and functional impact of key SNVs on viral pathogenesis.

Main Methods:

• Comparative analysis of newly collected SARS-CoV-2 genomes with previous data.
• Identification and tracking of SNV incidence ratios over time.
• Logistic regression modeling to identify mortality-associated features.
• Protein structure analysis to assess the impact of mutations.

Main Results:

• Remarkable shifts in SNV clustering observed since June 2020.
• Emergence of dominant SNV groups (e.g., S:D614G, ORF1ab:P4715L) and new groups with high incidence.
• Identification of SNVs, age (>40), and male gender as significant predictors of mortality.
• Mortality-related SNVs located on protein surfaces, potentially altering conformation, transmission, and virulence.
• Nonsynonymous SNVs found in disordered regions of Spike and ORF1ab, increasing hydrophobicity and possibly aiding immune evasion.

Conclusions:

• SARS-CoV-2 evolution is characterized by dynamic SNV clustering and the emergence of potentially more virulent strains.
• Specific SNVs, combined with host factors like age and gender, are critical determinants of COVID-19 mortality.
• Structural analysis suggests mutations impact viral pathogenesis, transmission, and immune evasion through altered protein properties.