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Molecular Characterization of Persistent SARS-CoV-2 Infections in Immunocompromised Patients.
Patricia Volkow-Fernández1, Marco Villanueva-Reza2, Santiago Ávila-Ríos3
1Department of Infectious Diseases, Instituto Nacional de Cancerología, Mexico City 14080, Mexico.
Viruses
|February 27, 2026
Summary
Persistent SARS-CoV-2 infection in immunocompromised patients can lead to sustained viral evolution. Genomic analysis reveals ongoing viral replication and mutation accumulation during long-term COVID-19.
Area of Science:
- Virology
- Immunology
- Genomics
Background:
- Immunocompromised individuals face higher risks of persistent SARS-CoV-2 infection.
- Long-term viral shedding is known, but intra-host viral evolution remains poorly understood.
Purpose of the Study:
- To investigate the extent and nature of SARS-CoV-2 intra-host evolution in immunocompromised patients with persistent infection.
- To analyze genomic changes in the virus over extended periods in these individuals.
Main Methods:
- Longitudinal whole-genome sequencing of SARS-CoV-2 from three immunocompromised patients with prolonged COVID-19.
- Detection of replication-competent virus over extended periods.
Main Results:
- Persistent SARS-CoV-2 infection was observed for up to 4 years in the studied cases.
- Sequential sequencing showed gradual accumulation of non-synonymous mutations across viral genes.
- Ongoing viral replication and intra-host diversification were evident due to impaired immune control.
Conclusions:
- Persistent SARS-CoV-2 infection in immunocompromised hosts can drive sustained viral evolution.
- Highlights the need for continued virological monitoring in patients with prolonged infections.
- Contributes to understanding SARS-CoV-2 dynamics in immunocompromised settings.
