Immunosuppression as a Hub for SARS-CoV-2 Mutational Drift

Area of Science:

• Virology
• Genomics
• Immunology

Background:

• The clinical course of coronavirus disease 2019 (COVID-19) varies widely, influenced by host factors.
• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to evolve, developing variants of concern (VOCs) that evade immunity.
• The origins and drivers of SARS-CoV-2 evolution, particularly VOCs, are not fully understood.

Purpose of the Study:

• To investigate the influence of host factors on the evolutionary trajectory of SARS-CoV-2 within infected individuals.
• To assess the impact of host clinical parameters and immunity on intra-host SARS-CoV-2 evolution.

Main Methods:

• Paired electronic health records with viral whole-genome sequences from SARS-CoV-2 infected individuals.
• Analysis of host clinical parameters, including vaccination status and smoking history.
• Assessment of intra-host viral diversity and mutational rates.

Main Results:

• Slight but significant differences in SARS-CoV-2 intra-host diversity were observed, correlated with host factors like vaccination and smoking.
• One case exhibited significant viral genome alterations: an immunocompromised woman with a prolonged infection showed accelerated mutation rates and truncated ORF3a.
• SARS-CoV-2 evolutionary capacity during acute infection appears limited and largely unaffected by typical host characteristics.

Conclusions:

• Significant SARS-CoV-2 evolution is rare and primarily associated with prolonged infections in immunocompromised individuals.
• These rare cases can accumulate impactful mutations, but their transmissibility remains uncertain.
• Host factors generally have a limited effect on viral evolution during acute SARS-CoV-2 infection.