Detection of respiratory viruses directly from clinical samples using next‐generation sequencing: A literature review of recent advances and potential for routine clinical use

Abstract

Acute respiratory infection is the third most frequent cause of mortality worldwide, causing over 4.25 million deaths annually. Although most diagnosed acute respiratory infections are thought to be of viral origin, the aetiology often remains unclear. The advent of next‐generation sequencing (NGS) has revolutionised the field of virus discovery and identification, particularly in the detection of unknown respiratory viruses. We systematically reviewed the application of NGS technologies for detecting respiratory viruses from clinical samples and outline potential barriers to the routine clinical introduction of NGS. The five databases searched for studies published in English from 01 January 2010 to 01 February 2021, which led to the inclusion of 52 studies. A total of 14 different models of NGS platforms were summarised from included studies. Among these models, second‐generation sequencing platforms (e.g., Illumina sequencers) were used in the majority of studies (41/52, 79%). Moreover, NGS platforms have proven successful in detecting a variety of respiratory viruses, including influenza A/B viruses (9/52, 17%), SARS‐CoV‐2 (21/52, 40%), parainfluenza virus (3/52, 6%), respiratory syncytial virus (1/52, 2%), human metapneumovirus (2/52, 4%), or a viral panel including other respiratory viruses (16/52, 31%). The review of NGS technologies used in previous studies indicates the advantages of NGS technologies in novel virus detection, virus typing, mutation identification, and infection cluster assessment. Although there remain some technical and ethical challenges associated with NGS use in clinical laboratories, NGS is a promising future tool to improve understanding of respiratory viruses and provide a more accurate diagnosis with simultaneous virus characterisation.

Significance of wastewater surveillance in detecting the prevalence of SARS-CoV-2 variants and other respiratory viruses in the community – A multi-site evaluation

“…[ 3 ] However, alternative and complementary technologies are also necessary for this effort as there exist barriers to the accessibility of sequencing technologies (i.e., rising costs and sizeable necessary sequencing volumes). [ 4 , 5 ] Furthermore, leveraging the SARS-CoV-2 monitoring to include co-occurring pathogens in the community, including other respiratory viruses that cause similar symptoms, is critical to accurately determine community health and disease prevalence.…”

Metagenomics characterization of respiratory viral RNA pathogens in children under five years with severe acute respiratory infection in the Free State, South Africa

“…17,18 Furthermore, mNGS enables pathogen subtyping/genotyping, identification of drug resistance markers, and molecular-based epidemiological studies. 9,19,20 Although recent studies have demonstrated the power of mNGS in diagnosing respiratory infection in different parts of the world, 6,9,14,21 the current data from South Africa/Africa at large on the clinical diagnostic utility of mNGS in SARI are still limited, 22 especially in comparison to the performance of mRT-PCR in paediatric patients. Additionally, the increasing need for prompt analysis of generated mNGS data has birthed several user-friendly, nontechnical, yet sensitive web-based mNGS bioinformatic analysis tools.…”

Detection of respiratory viruses in clinical samples

“…Future solutions to the existing NGS platform difficulties may result from the quick advancement of NGS technologies and bioinformatics pipelines [37]. Therefore, in the near future, we may anticipate that NGS technique will be predominantly used in wet lab for routine work at a cheap cost and providing more effective therapy, and monitoring new viruses [39].…”