# Chronic infections can generate SARS-CoV-2-like bursts of viral evolution without epistasis

## TL;DR

The study shows that chronic infections can lead to sudden bursts of mutations in viruses like SARS-CoV-2, even without epistasis.

## Contribution

The novelty is demonstrating that chronic infections alone can cause mutation bursts similar to SARS-CoV-2 without requiring epistasis.

## Key findings

- Chronic infections can produce SARS-CoV-2-like mutation bursts without epistasis.
- Chronic infections increase the global evolutionary rate of pathogens.
- The study supports chronic infections as a plausible origin for highly mutated SARS-CoV-2 variants.

## Abstract

Multiple SARS-CoV-2 variants have arisen during the first years of the pandemic, often bearing many new mutations. Several explanations have been offered for the surprisingly sudden emergence of multiple mutations that enhance viral fitness, including cryptic transmission, spillover from animal reservoirs, epistasis between mutations, and chronic infections. Here, we simulated pathogen evolution combining within-host replication and between-host transmission. We found that, under certain conditions, chronic infections can lead to SARS-CoV-2-like bursts of mutations even without epistasis. Chronic infections can also increase the global evolutionary rate of a pathogen even in the absence of clear mutational bursts. Overall, our study supports chronic infections as a plausible origin for highly mutated SARS-CoV-2 variants. More generally, we also describe how chronic infections can influence pathogen evolution under different scenarios.