By mid-January 2021, the U.K., South Africa and Brazil had confirmed that “variants of concern” were driving massive surges in COVID-19 cases in their countries. Once alerted, other nations found these troubling strains rapidly multiplying within their populations as well. At the time, the world had reported 90 million cases, creating abundant opportunities for the coronavirus to mutate. Of those cases, the virus in just 360,000 had been sequenced – and nearly all of them from just a handful of countries.
In response to the rapid spread of the B.1.1.7, B.1.135, and P.1 (from the B.1.1.28 lineage) variants, WHO called on countries around the world to prioritize increasing sequencing capacity. “Our collective goal is to get ahead of the game and have a global mechanism to quickly identify and study variants of concern and understand their implications for disease control efforts,” said Ana Maria Henao Restrepo, head of WHO’s R&D Blueprint, at a meeting of 1,750 scientists from 124 countries.
Early in the pandemic, with no global surveillance system and many countries struggling to test, let alone sequence, researchers adapted a free and open global system for monitoring mutations in influenza viruses, GISAID, to report and track changes in the SARS-CoV-2 genome and their clinical and epidemiological impact. The open-source project Nextstrain.org, created by scientists at the Fred Hutchinson Cancer Research Center in Seattle and the University of Basel in Switzerland, ramped up to convert sequences shared via GISAID into a real-time snapshot of the evolution of the coronavirus by creating phylogenies for mutations, tagged by geography, that reveal the rise and spread of mutations and their growth rate.
While powerful tools, both GISAID and Nextstrain remain hampered by inadequate sequencing. Uploaded data has skewed heavily toward certain countries; 140 countries have added genomic data to GISAID, but the U.K. accounts for 45% of the sequences and Denmark for 7%. That’s not for lack of sharing; it’s for lack of sequencing. The U.K. sequences 5% of cases and Denmark 12%, while Australia and New Zealand sequence nearly 60% and 50% of their (relatively few) cases, respectively. The U.S., by comparison, was sequencing just 0.3% at the beginning of 2021. A number of countries in Africa have no genomics data, yet Gambia, Equatorial Guinea and Sierra Leone have sequenced at a higher rate than the U.S., France or Italy, The Lancet reported.
Industry steps up
While many governments committed to increasing genomic surveillance in January, industry took action to make it happen.
Illumina Inc., for instance, “is actively working with more than a dozen organizations on the need for a global surveillance system so that each country may understand what variants they have present in the population and can effectively execute global control measures,” company spokesperson Lizelda Lopez told BioWorld. “And we are engaged with a robust and growing coalition of willing partners – public, academic, and private institutions – that can rapidly deploy national genomic surveillance at scale.”
Illumina’s biostatistical work demonstrated that sequencing 5% of positive cases would identify emerging strains when they accounted for just 0.1% to 1% of active cases. In line with that estimate, the European Union called on countries to commit to sequencing 5% of all positive COVID-19 test results at a minimum, with a goal of 10% preferred.
“We can achieve this if we have national support, funding for centralized laboratories, standard reporting of data, and include collection and sequencing from underrepresented communities most impacted by this pandemic,” Lopez added. In a letter to the Biden Administration just before the inauguration, Illumina and 13 other entities said that with those four actions, they could scale up sequencing in their facilities from just over 3,500 to 61,000 per day within 10 weeks.
Consortia can push governments toward national and global goals, but substantially increasing sequencing also requires significant changes in the processes used. Companies around the world have accepted the challenge. South Korea’s Seegene Inc., for example, dramatically simplified identification of variants with its Allplex SARS-CoV-2 Variants 1 Assay which can detect and differentiate known and suspicious new variants in a single tube of reagent. Seegene is prioritizing supplying its COVID-19 variant tests to global organization and governments.
Meanwhile, France’s Novacyt SA’s bioinformatics surveillance group, working with virologists in the U.K., U.S. and Latin America, identified the mutations or single nucleotide polymorphisms (SNPs) critical to each of the current concerning variants and deployed the SNPsig portfolio for detection and genotyping. “The consortium will reinforce existing surveillance program and establish some new surveillance networks in key geographical locations in which new variants appear to arise,” Novacyt’s CEO Graham Mullis said.
Researchers at Yale University and Tempus Labs Inc. in Chicago developed an open source PCR assay to detect and differentiate between the U.K., South African and Brazilian variants. Swift Biosciences Inc.’s Swift Normalase Amplicon SARS-CoV-2 S Gene Panel (SNAP) allows “researchers to sequence a higher number of samples more quickly by eliminating the tedious, time-intensive qPCR library quantification step” usually required to find rare transcripts, Swift’s Director of Manufacturing Sciences Jordan Rosefigura said. With SNAP’s rapid protocol, researchers can go from cDNA to sequencer in three hours and know within 24 hours which strains are in local circulation.
Integrated DNA Technologies Inc. (IDT) took a different tack and focused on “improving the methods for enriching for the SARS-CoV-2 viral genome,” including designing new approaches to developing and sequencing alternative amplicons, said IDT's Mirna Jarosz, general manager of Next Generation Sequencing. Amplicon sequencing looks for genetic variation in specific genomic regions.
“The great thing about most of the current enrichment methods (hybridization capture, ARTIC and Midnight amplification panels) is they all show good data across the various strains of concern (past and present),” Jarosz told BioWorld.
Italy’s Dante Labs Ltd. invested £30M (US$41.49 million) to operate a global surveillance program in the U.K. with the capacity to analyze 50,000 samples per week on its Immensa Genome Platform. “Today, we offer a global solution for complete surveillance at scale, giving a huge advantage to governments and organizations that won’t need to learn sequencing and sequencing interpretation from zero,” Dante’s CEO Andrea Riposati said. The platform uses AI to detect the current strains and identify new variants as they emerge.
All these efforts are important salvos in the battle against SARS-CoV-2, but still leave the world with inadequate intelligence to conduct a war on multiple fronts. For that, true global surveillance and cooperation are required.