Respiratory viral co-infections among SARS-CoV-2 cases confirmed by virome capture sequencing

Ki Wook Kim,Maria E Craig,Marc R Wilkins,Zin Naing,Thiruni Adikari,Alicia G Beukers,David Mcfarlane,Simon Yin,Ira W Deveson,Chi Nam I Pang,Rowena A Bull,William D Rawlinson,Malinna Yeang,Jillian M Hammond,Sebastiaan J Van Hal,Sacha Stelzer-Braid,Andrey Verich,Igor Stevanovski

doi:10.1038/s41598-021-83642-x

Abstract

Accumulating evidence supports the high prevalence of co-infections among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients, and their potential to worsen the clinical outcome of COVID-19. However, there are few data on Southern Hemisphere populations, and most studies to date have investigated a narrow spectrum of viruses using targeted qRT-PCR. Here we assessed respiratory viral co-infections among SARS-CoV-2 patients in Australia, through respiratory virome characterization. Nasopharyngeal swabs of 92 SARS-CoV-2-positive cases were sequenced using pan-viral hybrid-capture and the Twist Respiratory Virus Panel. In total, 8% of cases were co-infected, with rhinovirus (6%) or influenzavirus (2%). Twist capture also achieved near-complete sequencing (> 90% coverage, > tenfold depth) of the SARS-CoV-2 genome in 95% of specimens with Ct < 30. Our results highlight the importance of assessing all pathogens in symptomatic patients, and the dual-functionality of Twist hybrid-capture, for SARS-CoV-2 whole-genome sequencing without amplicon generation and the simultaneous identification of viral co-infections with ease.

Highlights

Accumulating evidence supports the high prevalence of co-infections among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients, and their potential to worsen the clinical outcome of COVID-19
Our results highlight the importance of assessing all pathogens in symptomatic patients, and the dualfunctionality of Twist hybrid-capture, for SARS-CoV-2 whole-genome sequencing without amplicon generation and the simultaneous identification of viral co-infections with ease
Despite this evidence supporting the high prevalence of co-infections among SARS-CoV-2 cases and its potentially substantial clinical impacts on COVID-19, existing data on co-infection remain limited by the low representation of the global population and the small number of viruses examined

Summary

Introduction

Accumulating evidence supports the high prevalence of co-infections among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients, and their potential to worsen the clinical outcome of COVID-19. Our results highlight the importance of assessing all pathogens in symptomatic patients, and the dualfunctionality of Twist hybrid-capture, for SARS-CoV-2 whole-genome sequencing without amplicon generation and the simultaneous identification of viral co-infections with ease. A higher prevalence of co-infection is reported among COVID-19 patients with more severe onset of disease[3] and the deceased[4], suggesting that co-infections can significantly worsen the clinical outcome of COVID-19 Despite this evidence supporting the high prevalence of co-infections among SARS-CoV-2 cases and its potentially substantial clinical impacts on COVID-19, existing data on co-infection remain limited by the low representation of the global population and the small number of viruses examined. This demonstrated the utility of such a process, and greater WGS coverage achieved using hybrid-capture sequencing over existing amplicon-based procedures in situations where primer binding sites are abolished by genomic deletions

Methods

Results

Conclusion