Thanks to its availability and affordability, next-generation sequencing (NGS) has been an integral component of the scientific community’s response to the COVID-19 pandemic. Genomic data has enabled unprecedented pathogen surveillance and rapid development of diagnostic tests and vaccines based on the viral genome sequence.

The very first look at the SARS-CoV-2 genome came from scientists at the Shanghai Public Health Clinical Centre at Fudan University. A team led by Prof Yong-Zhen Zhang sequenced an isolate collected on 26 Dec 2019 from a patient in Wuhan; they completed the genome assembly on 5 Jan 2020. That genome sequence was shared with the team’s longtime research partner, virologist Prof Eddie Holmes at the University of Sydney. He uploaded the sequence to a public database on January 11, introducing the world to the organism’s genome.

That sequence data was immediately deployed for vaccine development efforts, laying the foundation for the first two mRNA vaccines ever used outside of clinical trials. It also served as the basis for many of the SARS-CoV-2 diagnostic tests used today.

But the sequencing efforts did not stop there. By early 2021, more than 600,000 virus genomes had been sequenced and publicly shared in the GISAID database [1]. That’s more genome sequences ever generated for any pathogen in such a short time period. This remarkable collection of data has allowed scientists to track the spread of the virus, map transmissions based on phylogenetic data, measure its mutation rate, spot emerging variants of concern, and identify super-spreader events.

None of those achievements would be possible without whole genome sequence data generated from so many isolates. In countries such as the United States and United Kingdom, laboratories have established sequencing workflows [2] designed to accommodate the low-volume residual samples left over after molecular diagnostics assays have been run. While the pandemic has been utterly devastating, the contributions of NGS data from laboratories around the world have marked a kind of golden age for viral genomics.

Scientists in Japan, for example, have produced and publicly shared tens of thousands of SARS-CoV-2 genome sequences. That information allowed them to spot the local introduction [3] of emerging variants initially identified in the UK, South Africa, and Brazil — variants that are more contagious than the original strain and may reduce the effectiveness of certain vaccines. Sequences recently deposited to public databases from Japan came from Nagasaki University, the National Institute of Infectious Diseases, and Ibaraki Prefectural Institute of Public Health.

Other recent genome sequence contributions from the Asia Pacific region [4] came from Bangladesh, Brunei, China, Hong Kong, India [5], Indonesia [6], the Philippines, South Korea, and Australia. Some institutions are using social media to keep residents up to date. For instance, the Philippine Genome Center recently tweeted: “The SARS-CoV-2 variant bearing multiple mutations of concern in the spike protein region has been first detected via whole genome sequencing at PGC’s DNA Sequencing Core Facility and genomically characterized in the PH, and was officially designated as Lineage P.3 on 03/10/2021.”

Countries sequencing a representative proportion of their COVID-19 cases are providing critical information about how the virus is evolving and which mutations may be most worrisome. For example, the B.1.1.7 variant originally detected in the UK and the B.1.351 variant originally found in South Africa both contain far more mutations than expected [7] based on standard evolution rates for SARS-CoV-2, leading scientists to speculate that these more contagious variants may have evolved within patients suffering from a prolonged infection [8]. The high number of mutations could reflect a virus that has responded to significant and repeated selective pressure from an immune system.

In some countries, NGS tools have also been deployed for community surveillance programmes, often based on wastewater [9]. Trends seen in viral diversity and volume in a neighborhood’s wastewater often presage what will be seen clinically in those regions a few weeks later; this information can help guide public health policies, especially for mitigation measures such as regional lockdowns.

Separately, a volunteer-driven project known as MetaSUB [10] uses metagenomic sequencing of samples collected from public places such as transit systems in cities around the world. For the past year, those samples have included SARS-CoV-2 genomes, with data largely matching the clinical trends seen in those regions.

“As more countries move to implement sequencing programmes, there will be further opportunities to better understand the world of emerging pathogens and their interactions with humans and animals in a variety of climates, ecosystems, cultures, lifestyles and biomes,” wrote Sylvie Briand, Director of Global Infectious Hazard Preparedness at the World Health Organisation in a recently released guide to using genome sequencing for SARS-CoV-2 [11]. “The accelerated integration of genome sequencing into the practices of the global health community is a must if we want to be better prepared for the future threats.”

The COVID-19 pandemic has highlighted the value of whole genome sequencing as well as the need for proactive infectious disease surveillance to detect new, emerging diseases before they spread around the world. It will be essential to invest appropriate resources and build up surveillance infrastructure to ensure that we are better prepared for the next pandemic threat.

Genomic surveillance and epidemiology is just one example of how laboratory diagnostics are supporting COVID-19 management. To learn more about the full spectrum of opportunities, check out The Critical Role of Diagnostics in COVID-19 Management, a new report by the Asia Pacific Medical Technology Association (APACMed). 

References:

[1] GISAID Database

[2] Sequencing COVID-19 at the Sanger Institute, The Sanger Institute Blog

[3] The Critical Role of Diagnostics in COVID-19 management, APACMed

[4] Genomic epidemiology of novel coronavirus – Asia-focused subsampling, Nextstrain

[5] “Coronavirus: India hunts for new strains as Covid wave looms”, BBC

[6] “Indonesia ramps up efforts to spot elusive COVID variants”, Nikkei Asia

[7] “The most worrying mutations in five emerging coronavirus variants”, Scientific American

[8] “‘An accelerated cauldron of evolution’: Covid-19 patients with cancer, HIV, may play a role in emergence of variants”, The Washington Post

[9] “Tracking COVID-19 with wasterwater”, Nature Biotechnology

[10] MetaSUB consortium

[11] World Health Organisation Guidelines on Genomic Sequencing of SARS-CoV-2