NGS: Hot on the Trail

COVID-19 brought infectious disease management and research into the public eye, illustrating how crucial these tools are for combating current and future pandemics. The implementation of next-generation sequencing (NGS) has been key to these efforts, allowing scientists to detect and track the spread of new variants. Indeed, with its breadth of information and ability to show genomic structural changes, NGS has become crucial for tracking the evolution of SARS-CoV-2 and other viruses. The smaller size of viral genomes makes them easier to sequence than other pathogens, but NGS can also be more precisely targeted to biologically important regions – such as antibiotic resistance genes – when it comes to larger pathogen genomes.

By revealing insight into the genetic structure of a pathogen, NGS allows mutations to be tracked and for the development of new strains to be monitored. Right now, NGS serves two main applications within the infectious disease community: individual patients and wastewater surveillance. At the patient-level, sequencing reveals not only what pathogen the patient has, but also the strain – allowing us to track a disease through the population, while observing how its structure and clinical presentation evolves. This has been particularly useful during the COVID-19 pandemic; NGS has been used to track the evolution of the SARS-CoV-2 spike protein and detect new variants able to evade vaccine immunity. Tracking spike protein mutations using NGS also allowed new vaccines to be developed to address these changes.

A new frontier for public health

By sampling from a pool of DNA from a particular population, NGS-based wastewater surveillance – a relative newcomer to the field – can reveal which pathogens are present in that population and serve as a warning signal for emerging outbreaks. It is particularly useful when regional testing efforts are low and an outbreak could be spreading undetected; by identifying a pathogen using wastewater surveillance, health officials can make informed decisions and mobilize a response more quickly.

Using NGS for assessing individual patients goes hand-in-hand with population sequencing. Both inform public health officials on the pathogen behind current outbreaks and alert them about emerging waves and, together, they provide the information needed to quickly launch an effective response.

Despite its importance in public health, broad adoption of wastewater surveillance presents significant challenges. The first challenge is economic – unsurprisingly, sequencing efforts require a source of funding. Fortunately, some government bodies have stepped up to the plate, but there is still a way to go. 

The second challenge is technical. Determining the optimal sequencing method – direct, amplification, or hybrid capture – for each situation can be difficult. The third challenge is procedural – we need to address how we handle potentially infectious samples at scale. The safety of those working with these samples is of utmost importance when developing a sensitive assay. Some labs have faced issues when trying to sequence mpox or polio samples because they don’t have the biosafety certifications required to handle those types of samples.

The future utility of NGS

It’s not hard to see why surveillance activities will increase significantly in the coming years – boosted by their effectiveness during the COVID-19 pandemic. Notably, there will be more pathogens and antibiotic resistance markers being screened as we try to understand the probability of a potential outbreak. There has been a surge of interest in global research networks that enable sharing of data across a range of viruses to extract insights that could be applied to future epidemics.

Additionally, patient sequencing could find new uses in future – for example, sequencing the pathogens from those who are not responding well to treatment. Testing could reveal that they have a different strain that evades the drug’s potency, while genomic information might provide clues about the mechanism of resistance and support the development of new therapies for patients with drug-resistant infections.

Over the years, NGS has developed into an important tool for the infectious disease community – from detecting and sequencing pathogens to tracking them through the population and identifying outbreaks early. The information generated from NGS gives health officials time to educate the public and spring into action with interventions to curb disease spread. Going forward, the ID community is pushing for a more collaborative approach to establish networks that will advance the field even further – working with researchers, policymakers, and industry leaders to improve NGS research assays, form cross-discipline collaborations, and promote continuous conversation on improving infectious disease research and management.