Exploring the Role of Viral Genomics in Pandemic Preparedness
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The recent global health crisis shone a light on the potential of viral genomics for informing the development of new tests, vaccines and monitoring programs that contribute to disease prevention and infection control efforts. This emerging field is now gaining traction through pioneering labs and health institutions, which are using genomic sequencing and phylogenetic analyses to infer possible transmission chains and identify new strains of other highly contagious viruses.
This article discusses why the proactive detection and monitoring of viral threats through genomics studies is vital in preventing future pandemics and empowering healthcare providers in the face of increasing globalization. It will also present some of the practical limitations faced by genomics laboratories, such as liquid handling bottlenecks, and the directions this rapidly evolving field may take in the coming years.
Highlighting the value of viral genomics: a case in point
The Center for Emerging Viral Threats (CEVT) in Shreveport, Louisiana, was established at the start of the COVID-19 pandemic to perform rapid PCR testing, support vaccination development and carry out viral sequencing. It quickly began to build a library of complete SARS-CoV-2 genome sequences from community mid-turbinate and saliva samples, which it used for phylodynamic analysis of the local outbreak. The center has now sequenced over 18,000 viral samples since March 2020 – covering 3,882 unique genomes – and this vast wealth of genetic data has provided crucial insights into both the mechanism of infection and evolution of SARS-CoV-2. Sequencing data is still regularly uploaded to GISAID, an international data-sharing platform that has been a key resource for getting the upper hand over COVID-19 and various types of influenza. This valuable information contributes to international efforts to better understand the SARS-CoV-2 virus and its emerging variants, enable molecular epidemiology work – such as contact tracing and incidence mapping – as well as informing future vaccine and annual booster development.
The CEVT has also been analyzing wastewater specimens to monitor the spread of COVID-19 across northwest Louisiana throughout the pandemic, observing that an increase in the presence of SARS-CoV-2 in wastewater often predicted a rise in case numbers. This acted as an early warning system to health institutions, giving them the opportunity to take the proper measures necessary to equip themselves for a potential influx of patients needing treatment and possibly hospitalization.
In addition to its varied surveillance activities, the group is currently working on several projects to elucidate the seasonality of the COVID-19 disease and study its pathology. For instance, researchers are cooperating with nearby health institutions to understand why some individuals experience more severe symptoms than others. Sequencing patient samples identifies the specific SARS-CoV-2 variant, subvariant or hybrid present, and indicates any unique genetic features that cause it to be particularly aggressive or to interact with other person-specific factors.
The center’s sequencing data is also valuable in guiding the development of booster vaccines that are effective against the newest mutations in circulation, ensuring that the vulnerable segments of the population remain protected year after year. Alongside this, the lab is running educational programs within the local communities, spreading the word about its efforts to support public health decisions and control COVID-19 and other infectious viral diseases prevalent in the area. This outreach work has been useful in informing residents how they can protect themselves and plays a role in helping to prevent and contain any new infection waves in the state.
Adapting to the need with innovative solutions
The pioneering facility has built on the many lessons learned from the pandemic and has been gradually broadening its work since the pressure of rapid PCR testing began to ease off. The CEVT is now a surveillance center for the detection and monitoring of other viral threats – such as influenza, respiratory syncytial virus (RSV) and mpox – processing swabs from hospitals, schools and correctional facilities around Louisiana. It is also routinely testing wastewater samples to understand the epidemiology of circulating diseases and their relationships to existing pathogens. This data is vital in advising infection control measures, such as publicity campaigns and screening programs, and also speeds up the process of developing effective treatments and vaccines, further aiding in the prevention of widespread outbreaks in the long term.
The manual transfer of liquids between different labware types was initially a huge pain point for the small laboratory team, as it was an extremely time-consuming and error-prone process. Meeting the demand for rapid PCR testing, therefore, presented a challenge, motivating the group to acquire electronically adjustable tip spacing pipettes from INTEGRA to streamline sample transfer and reformatting steps and remove liquid handling bottlenecks. The novel pipettes enable the lab staff to process multiple samples between different labware formats at once, and their high precision and reproducibility has helped to avoid the need to repeat pipetting protocols. This proved vital for saving time and maximizing lab throughput, making it possible to maintain short turnaround times for COVID-19 testing.
The genome sequencing lab at the CEVT also uses intuitive VIAFLO and MINI 96 pipettes for sample transfers and bead clean-up within viral genomics workflows, enabling rapid sequencing of large numbers of viral samples to build a picture of disease prevalence and contribute vital data to vaccine development efforts. The lab has even recently acquired an ASSIST PLUS pipetting robot for full workflow automation, helping it to manage its growing workload and develop novel testing workflows. This setup will give the group the flexibility and capacity it requires to build these important new projects and keep up with the demand for testing and viral sequencing going forward.
Emerging trends in pandemic prevention
Governments and public health institutions are now more aware than ever of being ready for whatever the future may hold, and large-scale programs like wastewater community monitoring will prove vital in pre-emptive disease control measures going forward. Much effort is also being invested in making next-generation sequencing (NGS) more portable, with the goal of producing highly accurate miniaturized sequencing technologies that can be taken to the point of use for rapid on-site testing. This would help to avoid the many logistical and financial issues related to collecting and transporting samples between test sites and genomics centers, particularly when dealing with samples from rural and isolated populations.
Analyzing this genomics data is often a choke point for smaller groups that don’t have the expertise, time or software needed to perform large-scale, high-complexity analyses on their sequencing results. This common difficulty has sparked interest in the development of new open-source software offering graphical user interfaces that will make high-quality statistical analysis accessible to a wider range of researchers all over the world, accelerating advancement in the field of genomics.
Viral surveillance also seems to be moving towards a more agnostic approach, using NGS to identify every pathogen present in a single sample. A targeted assay relies on having prior knowledge of a pathogen’s genome, meaning that it will not be able to detect any unknown organisms. However, metagenomic techniques can non-specifically sequence all detectable viral nucleic acids present, regardless of whether or not the virus’ genome has previously been completed. Viral metagenomics is still not widely used as a diagnostic tool due to a number of factors, and further studies are most certainly needed in order to bring this revolutionary technique into the mainstream, but the method shows promise for supporting a robust disease control response right from the start of an outbreak.
A multidisciplinary approach to disease control
As well as technological advancements, there is also a pressing need to provide universities and research labs with regular educational programs and ongoing support, helping to increase the level of professional proficiency in genomic sequencing and enhance understanding regarding viruses and the diseases they cause. Similarly, it is becoming increasingly crucial to promote collaboration between different research, clinical and even governmental institutions, in order to pool resources and guide timely and appropriate public health decisions that will protect the population in the years to come.
The ever-changing nature of SARS-CoV-2 highlighted the need for high-quality, rapid full genome sequencing to support disease control efforts, and accelerated knowledge and skills in the field of viral genomics at an unprecedented rate. Electronic pipettes became must-have tools for the team at the CEVT, and empowered the lab to increase sample throughput, expand experimental protocols and meet the demand for rapid testing in the face of an ever-changing epidemiological landscape. Only time will tell how the area will evolve in the future, but the global health crisis has finally brought it some of the attention and focus it deserves, giving hope that groundbreaking new discoveries may soon appear on the horizon.
About the author:
Krista Queen, PhD, is the director of Viral Genomics and Surveillance at the Center of Excellence for Emerging Viral Threats at LSU Health Shreveport, Louisiana, USA. With a research background in virology, pathogen discovery and sequencing applications, Dr. Queen focuses on genomic surveillance of respiratory viruses and emerging pathogens, including wastewater surveillance. Prior to her current role, Dr. Queen worked at the US Centers for Disease Control and Prevention from 2013 to 2021, where she played a key role in the sequencing activities for MERS-CoV and SARS-CoV-2, while also focusing on pathogen discovery and detection.