# Disentangling SARS-CoV-2 Sustained Viremia Cases: Evolution, Persistence and Reinfection

## TL;DR

This study examines how SARS-CoV-2 behaves in cancer patients over time, identifying cases of persistent infection, reinfection, and multiple infections.

## Contribution

The study is the first to analyze SARS-CoV-2 within-host minor variants and describe viral evolution in cancer patients.

## Key findings

- Nine confirmed and 12 plausible cases of persistent SARS-CoV-2 infection were identified.
- Three confirmed and two plausible reinfection cases were found, including one multiple infection.
- The study reveals virus evolution dynamics in intrahost populations for the first time.

## Abstract

Based on the follow-up of patients who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, several reports of people who re-tested positive have been described. This may result from viral reactivation, true reinfection, superinfection, or an initial infection by more than one virus (multiple infection). These scenarios can only be correctly distinguished through viral quasispecies analysis. Herein, 26 cancer patients under extended follow-up for SARS-CoV-2 infection were submitted to multiple longitudinal analyses through nucleic acid isolation, PCR amplification and high-throughput sequencing. SARS-CoV-2 classification and the definition of cases as persistent or repeated infections were based on phylogenetic reconstruction. Supported by their viral complete genomes and intrahost quasispecies over time, the different scenarios were identified. Nine confirmed and 12 plausible persistence cases were identified. Virus evolution dynamics in the intrahost population from patients with persistent infection was shown for the first time. Regarding reinfection, three confirmed and two plausible cases were identified, including one case of multiple infection. Altogether, this is the first study that analyzes the plethora of SARS-CoV-2 within-host minor variants and describes reinfections, multiple infections and viral evolution across time in cancer patients, contributing to the understanding of SARS-CoV-2’s within-host population dynamics in the natural history of COVID-19.