Impact of prolonged infection on SARS-CoV-2 evolution.
Fang Yan1,2, Qiushi Jin2,3, Yuanguo Li2
1College of Wildlife and Protected Areas, Northeast Forestry University, Harbin, China.
Microbiology Spectrum
|January 7, 2026
Summary
Immunocompromised patients with prolonged SARS-CoV-2 infections can drive viral evolution, leading to mutations that increase infectivity but decrease immune evasion. Monitoring these individuals is crucial for preventing the spread of new variants.
Area of Science:
- Virology
- Genomics
- Immunology
Background:
- Immunocompromised individuals with prolonged SARS-CoV-2 infections may act as reservoirs for viral evolution.
- Suboptimal immune responses in these hosts can facilitate the accumulation of adaptive mutations in the virus.
Purpose of the Study:
- To characterize the drivers of SARS-CoV-2 adaptive evolution in immunocompromised hosts through genomic surveillance.
- To identify and analyze specific mutations that arise during long-term infections.
Main Methods:
- Retrospective analysis of 24 patients with long-term SARS-CoV-2 positive PCR results.
- Phylogenetic analysis to track viral evolution.
- Identification and functional assays of intrahost single-nucleotide variants (SNVs).
Main Results:
- Accelerated viral evolution was observed in patients with underlying conditions like HIV and cancer.
- ORF1ab and the Spike protein coding region were identified as hotspots for mutations.
- A unique set of mutations, including Spike N440K/I794T, enhanced viral infectivity but reduced immune evasion.
Conclusions:
- Prolonged SARS-CoV-2 replication in immunocompromised hosts drives adaptive mutations with significant biological functions.
- The emergence of mutations like I794T, later found in JN.1.16, highlights potential evolutionary persistence.
- Close monitoring of immunocompromised patients is essential to detect and prevent the spread of neutralization-resistant variants.
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