Higher Levels of SARS-CoV-2 Genetic Variation in Immunocompromised Patients: A Retrospective Case-Control Study

Area of Science:

• Virology
• Immunology
• Genomics

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have prolonged durations in immunocompromised hosts compared to immunocompetent individuals.
• Extended infections increase the likelihood of novel SARS-CoV-2 mutations, particularly within the spike protein, a key target for vaccines and therapeutics.

Purpose of the Study:

• To investigate the genetic diversity of SARS-CoV-2 in immunocompromised patients compared to health care workers.
• To identify potential SARS-CoV-2 mutations arising during prolonged infections in immunocompromised individuals.

Main Methods:

• Whole-genome sequencing of SARS-CoV-2 from respiratory samples of 444 immunocompromised patients and 234 health care workers.
• Analysis of viral genetic diversity using custom scripts and Nanopore technology between December 2020 and September 2022.

Main Results:

• SARS-CoV-2 Delta and Omicron lineages were predominant. Viral genetic diversity was significantly higher in immunocompromised patients.
• Minor mutations in immunocompromised individuals' viruses evolved into signature mutations for later SARS-CoV-2 variants.
• SARS-CoV-2 genome evolution varied between upper and lower respiratory tracts in immunocompromised patients.

Conclusions:

• SARS-CoV-2 infection in immunocompromised patients is linked to elevated genetic diversity.
• This increased diversity may facilitate the emergence of new SARS-CoV-2 variants with potential immune evasion or altered virulence.