Science‘s COVID-19 reporting is supported by the Heising-Simons Foundation
Last month, Gytis Dudas was tracking a concerning new coronavirus variant that had triggered an outbreak of COVID-19 in his native Lithuania and appeared sporadically elsewhere in Europe and in the United States. Exploring an international database of coronavirus genomes, Dudas found a crucial clue: One sample of the new SARS-CoV-2 variant came from a person who had recently flown to France from Cameroon. A collaborator, Guy Baele of KU Leuven, soon identified six more viral sequences from people in Europe who had traveled there from Cameroon. But then their quest to pinpoint the variant’s origins hit a wall: Cameroon had only uploaded 48 viral genomes to the global sequence repository called GISAID. None included the variant.
With dogged legwork, Baele and Dudas, an evolutionary biologist at the Gothenburg Global Biodiversity Centre, learned another team had gathered as-yet-unpublished sequences from a COVID-19 outbreak among staff at a great ape program in the Central African Republic—near the Cameroonian border. Six people there carried the new variant.
Baele, Dudas, and their colleagues reconstructed the variant’s evolutionary tree and geographic spread, and concluded that it most likely arose in Cameroon, as they reported in a preprint on 8 May. They note that the variant carries a suite of mutations seen in other “variants of concern” that are more infectious or dangerous.
“It looked like the typical thing that should raise all red flags,” says Sébastien Calvignac-Spencer, an evolutionary biologist at the Robert Koch Institute whose team sequenced samples from the ape station. But Cameroon and neighboring countries, where the team inferred the variant might already be prevalent, had been blind to it.
The researchers say the story of this variant, designated B.1.620, holds a warning for the world: “The sequencing effort in Cameroon and other African countries is not enough,” says co-author Ahidjo Ayouba, a biologist at the French National Research Institute for Sustainable Development at the University of Montpellier. He is traveling to his native Cameroon next month to set up the country’s first next-generation sequencer. The emergence of new variants with deleterious mutations in countries with no regular sequencing “may become an alarming norm,” the researchers caution in their preprint.
It is not just Africa. Of 152 countries for which data were available as of 10 May, 100 had uploaded sequence data to GISAID for less than 1% of their reported cases (see map, p. 774). Among those, 51 countries, including large nations such as India, Indonesia, Russia, and Brazil, had uploaded sequences for less than 0.1% of cases. Ten wealthy nations accounted for 82% of the more than 1.4 million sequences in GISAID’s database. “We are working to change that,” says Frank Konings, leader of the World Health Organization’s (WHO’s) Virus Evolution Working Group.
Most countries with scarce sequencing also currently have little or no access to vaccines, and some have severe outbreaks. As the virus replicates unchecked, those regions can become breeding grounds for new mutants, which can then spread around the world. India, for example, is coping with a world-leading surge of cases. On 11 May, WHO labeled the new variant B.1.617, which arose in India and has spread to dozens of countries, a variant of concern. “Where the pandemic is currently unchecked is where we can expect that variants are on the rise,” Dudas says. “It would be much more interesting to sequence the last 1000 cases in the Central African Republic than the next 100,000 cases in Germany.”
Globally, the obstacles to systematic surveillance are daunting. State-of-the-art sequencers cost $335,000, and local scientists must be trained to use them. Many areas lack the roads, planes, and refrigeration needed to speedily transport samples. In India, “The issue is sampling: Somebody has to collect and ship the samples and provide the clinical data. That takes some time,” says Anurag Agrawal, director of the Council of Scientific and Industrial Research’s Institute for Genomics and Integrative Biology in New Delhi. And costly sequencing reagents need to be continually imported and may not always be available.
“We ordered … reagents [from a U.S. company] in November . They are arriving now!” says Senjuti Saha, a microbiologist at the Child Health Research Foundation in Dhaka, Bangladesh. “This is not an exception, rather it’s the rule.”
Saha is nonetheless pleased with a multilab effort that has allowed the country to scale up sequencing to 0.2% of 780,000 confirmed COVID-19 cases. “I don’t think [that number is] great,” she says. “But it was zero before. And we have never done this before.”
The effort is already paying off, most recently on 8 May, when two Bangladeshi patients who recently returned from India were found to be carrying B.1.617. Two days later, after a long meeting with scientists, Bangladeshi officials tightened quarantine at the border.
Other countries face geographical challenges. In December 2020, Brazilian scientists identified P.1, now a variant of concern globally, during a massive outbreak in Manaus, the capital of Amazonas state. But sequencing coverage is poor in places like the neighboring rainforest state of Acre and in Brazil’s northeast, says Ana Vasconcelos, a computational biologist at the National Laboratory for Scientific Computing in Petrópolis. She says just 25 genomes have been uploaded from Acre. She enlisted colleagues there to provide 100 samples, then found there was no dry ice, needed for transport. She finally received the samples last week, with the help of a French nongovernmental organization, the Mérieux Foundation.
Some experts have suggested nations aim to sequence virus from 5% of cases, but others say such goals are wrongheaded. “The world is getting too obsessed with numbers,” says Tulio de Oliveira, a computational biologist and director of the KwaZulu-Natal Research and Innovation Sequencing Platform at the University of KwaZulu-Natal, Durban. For example, he and South African colleagues identified the variant of concern that originated in South Africa soon after it arose by strategically sampling regions that had outbreaks.
De Oliveira and a huge team of other African scientists have now turned sparse sequence data in Africa into a big picture of how the virus has evolved within the continent. In a preprint posted on 13 May, based on nearly 9000 genomes collected in 33 African countries they found that SARS-CoV-2 arrived in African countries with travelers, mainly from Europe. As people traveled within Africa, the virus spread and then evolved into several key variants. “Although distorted by low sampling numbers and blind-spots,” the authors write, “the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.”
That’s true worldwide, Calvignac-Spencer says. “It’s not really possible that we go on being so selfish with genomic surveillance, with vaccines,” he says. “It’s not understanding our own best interests.”