# Host–Virus Interface in Persistent SARS-CoV-2 Infections: Viral Characteristic Evolution and Gene Expression Profiling Analysis

## TL;DR

This study explores how SARS-CoV-2 evolves and interacts with the immune system during prolonged infections, showing changes in infectivity and immune responses.

## Contribution

The study identifies viral mutations and host gene expression changes in persistent SARS-CoV-2 infections, linking them to immune escape and adaptation.

## Key findings

- Persistent SARS-CoV-2 infections show significant differences in infectivity between early and late phases.
- Early-phase infections trigger strong pro-inflammatory responses, followed by immune suppression.
- Genomic mutations in ORF1ab and the spike protein suggest adaptations for immune escape.

## Abstract

Persistent SARS-CoV-2 infections involve prolonged viral replication and immune system interactions, potentially driving viral evolution and immune escape. This study examines viral characteristics and host gene expression changes in persistent infections. The nasopharyngeal samples from four patients with persistent SARS-CoV-2 infections at Tottori University Hospital, Japan, were analyzed. Viral isolates were cultured, and infectivity was assessed using TCID50 assays. To investigate host responses, RNA sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs), and Gene Ontology (GO) enrichment analysis mapped affected biological pathways. Viral genome sequencing detected mutations associated with prolonged infection. The results showed significant infectivity differences between early- and late-phase infection. Gene expression analysis revealed a strong early phase of pro-inflammatory response (IL6, TNF, IL1B, CXCL10) followed by immune suppression. GO enrichment analysis highlighted inflammation and cytokine-mediated immune pathways. Genomic sequencing identified mutations in ORF1ab and the spike (S) protein, potentially aiding immune escape. The findings underscore that SARS-CoV-2 adapts during persistent infections, altering infectivity and immune responses. These highlight the need for continued monitoring of prolonged infections to mitigate immune escape and viral evolution.