Learning from the Pandemic: Making the Most of Genomic Surveillance in Low- and Middle-Income Countries

During the COVID-19 pandemic, whole genomic sequencing (WGS)-based surveillance played a key role in identifying variants of concern, investigating their spread and transmissibility, and facilitating the design and optimization of medical countermeasures, including diagnostic tools and vaccines. However, only a handful of low- and middle-income countries (LMICs) sequenced the recommended threshold of at least five percent of positive samples, and even after the pandemic, investment in genomic surveillance remains limited.

The Pandemic Fund has selected its first round of projects in July of this year, and so as countries consider how best to bolster their pandemic preparedness and response (PPR) systems, they must also confront critical questions regarding WGS-based surveillance. This includes assessing the costs and benefits of implementing WGS systems and their relative value when compared with other interventions to strengthen PPR.

To help answer these questions, the Indian School of Business’ Max Institute of Healthcare Management (ISB MIHM), in collaboration with CGD, conducted a study to assess the cost-effectiveness of WGS in India. It found WGS-based surveillance to be cost-effective across a broad spectrum of scenarios and identified key determinants of cost-effectiveness, including the sampling rate, variant characteristics, and the time of novel variant’s emergence. The centralized approach showed a minimal advantage for variant detection over the decentralized approach in most scenarios and was always costlier to operate. Increasing sequencing capacity reduced the variant detection time only when a large proportion of positive samples were sequenced but incurred a higher cost of operation even when it was ineffective.

CGD hosted an online event to delve into the results of the research and discuss the wider implications of WGS on pandemic preparedness, prevention, and mitigation response efforts in LMICs. This blog covers four key takeaways from the discussion.

1. Genomic sequencing must be incorporated into broader surveillance systems to maximize value for money and optimize long-term sustainability

The question of whether countries should invest in WGS has a clear answer—they should. The main challenge is how to expand WGS-based surveillance capabilities beyond use in identifying and tracking viruses with pandemic potential to maximize value for money. WGS can, and should, be applied to antimicrobial resistance, pest management for crops, understanding livestock and crop disease, and environmental, vector, and wastewater surveillance, among other uses.

Expanding WGS to as many uses as possible will keep the engine running continuously and optimize long-term sustainability. Also, a wide variety of uses with supporting evidence will help policymakers invest in increasing WGS capacity while maximizing the value of these investments.

2. Local genomic sequencing holds the greatest value, yet a comprehensive evaluation of regional and global costs and benefits is essential

The COVID-19 pandemic served as an effective trial for WGS-based surveillance, prompting a rapid, reactive expansion of sequencing capacity worldwide. However, with the benefit of hindsight, policymakers can now adopt a more intentional and strategic approach. When doing so, they should address critical questions, including the optimal location for sequencing, the appropriate level on which to conduct it, and whether to centralize or decentralize WGS initiatives.

Some evidence suggests that local sequencing may lead to more timely and informed decision-making. Local sequencing enables countries to tailor their efforts to address specific national needs and to integrate genomic data with clinical and epidemiologic information. Moreover, when sequencing occurs locally and countries have ownership of the data, it is more likely to alleviate concerns related to data sharing, as opposed to shipping samples to high-income countries for sequencing. Despite the compelling arguments favoring localizing sequencing efforts, it is essential to recognize that sequencing has regional and global benefits. As a public good, it necessitates funding and support that extends beyond the scope of individual national governments.

In summary, there is no one-size-fits-all approach, and finding the optimal balance requires careful consideration of local, regional, and global costs and benefits.

3. Policymakers must build interconnected networks and make use of peacetime

Building networks, fostering collaboration, and establishing a pathogen genomic surveillance system during peacetime is critical. This proactive approach ensures that the necessary systems and capacity are in place for when the next pandemic strikes—the world cannot wait to act on a new variant. This interconnected network should extend beyond collaborations between high-income countries and LMICs to encompass partnerships among LMICs. Countries should share unique experiences and surveillance models, thus harnessing capacity and identifying and implementing best practices. One such example is the International Pathogen Surveillance Network, which aims to leverage existing capacity in a country while interconnecting the efforts of the countries in the network. The Global Initiative on Sharing All Influenza Data, implemented in 2008 to share genome sequencing data and which was widely used during the COVID-19 pandemic by researchers and policymakers across the globe, is another example.

4. More work is needed to understand cost-effectiveness for low- and middle-income countries

Data on the cost-effectiveness of surveillance programs, including WGS approaches, is limited, and precise “best buys” have yet to be identified. Significant work remains to understand the complexities and trade-offs associated with various tools and approaches.

Determining the most sustainable capacity for any country within a functional network is crucial to conducting a comprehensive cost analysis and alleviating uncertainty surrounding the value for money in surveillance. The key variables in the cost-benefit analysis of a pathogen genomic surveillance network depend on how the network is used and for what purpose. A critical variable to consider is the appropriate sampling rate, particularly in anticipation of varying modes and speeds of transmission, severity levels, and the required scale of response (e.g., national, regional or global). Calculating the appropriate sampling rates for each pathogen in each country requires consideration of epidemiological principles. Currently, only a few countries have the capability to integrate genomic data with epidemiological data, highlighting the need for expanded data collection to empower more countries in this regard.

Additionally, countries continue to face the challenge of both over- and under-investing in this technology. Further analysis is needed to establish the optimal investment amount for two reasons: firstly, it might displace other more critical, cost-effective testing or treatment options; and secondly, the global health benefits of WGS-based surveillance are not yet fully understood and quantified.

Genomic sequencing has proved to be a powerful tool for disease surveillance during the COVID-19 pandemic. In the future, there will be a pressing need for a deliberate and strategic expansion of WGS capacity, coupled with enhanced integration of this technology into broader surveillance systems in LMICs. Doing so will maximize its value for money and sustainability as a technology within the broader agenda of PPR. Stay tuned for forthcoming research from ISB MIHM and CGD on informing investment for cost-effective WGS-based surveillance strategies in India.

You can watch a full recap of the event here.