Immune Suppression, Preexisting Immunity, and Mutation Tendency Shaped SARS-CoV-2 Evolution in Persistent Infection.

Area of Science:

• Virology
• Immunology
• Genetics
• Public Health

Background:

• Persistent SARS-CoV-2 infections, particularly in immunocompromised hosts, act as reservoirs for viral evolution and the emergence of new variants.
• Understanding viral evolution mechanisms is critical for developing effective public health strategies and vaccines, especially for vulnerable populations.
• Long COVID-19 may be linked to viral evolution within persistent infections.

Purpose of the Study:

• To investigate the evolutionary and mutational profiles of SARS-CoV-2 variants within persistent infections.
• To identify factors influencing intra-host viral evolution rates.
• To assess the potential for persistent infections to generate variants of concern or interest.

Main Methods:

• Employed next-generation sequencing and phylogenetic analyses.
• Analyzed serial oropharyngeal swab samples from five individuals with persistent SARS-CoV-2 infections.
• Compared evolutionary patterns and mutation rates across different host immune statuses.

Main Results:

• Significant variation in intra-host evolutionary patterns was observed.
• Evolutionary rates in three immunocompromised hosts were 20 times higher than in two other patients, linked to immune suppression and mutation extent.
• Identified 15 intra-host single-nucleotide variants (iSNVs) in the spike gene, indicating convergent evolution, with some mutations aligning with variants of concern/interest.

Conclusions:

• Persistent infections are significant sources for novel, potentially harmful SARS-CoV-2 variants.
• Viral evolutionary dynamics are influenced by a complex interplay of virological, immunological, and genetic factors.
• Highlights the urgent need for individualized monitoring of immunocompromised hosts to prevent outbreaks and study sequelae.