COVID appears to be in retreat in the U.S. and other nations that have widespread access to vaccines. But some developing countries with high infection rates have become hotspots for viral variants that may be more transmissible or resistant to vaccines—and these variants can quickly cross national borders. For example, the B.1.167.2 variant (now dubbed Delta) that was first detected in India has spread to more than 70 countries and regions, including the U.S.
Much of the developing world lacks the capacity for viral surveillance—efforts to monitor the spread and evolution of new variants. This process requires expensive genomic-sequencing technology and trained workforces that many nations do not have. Nepal, for instance, has sequenced just 0.01 percent of the more than 600,000 cases reported in the country so far. New variants could undo hard-won progress in curbing the pandemic, according to Alina Chan, a postdoctoral fellow specializing in gene therapy and cell engineering at the Broad Institute of the Massachusetts Institute of Technology and Harvard University. “Variants that evolve to be able to reinfect previously infected people are likely to also reduce the efficacy of vaccines,” she says.
Scientists and organizations around the world are now working to build capacity to hunt for variants in developing countries. They are mobilizing to deliver funds, training and equipment to where these resources are needed most, with aspirations of creating a lasting viral surveillance infrastructure. “COVID is the catalyst,” says Jairo Mendez-Rico, a microbiologist and adviser on viral diseases at the Pan American Health Organization (PAHO), headquartered in Washington, D.C. “But we also need to survey for other pathogens that for sure will come in the future.”
In India, 27 laboratories have now banded together to create the Indian SARS-CoV-2 Genomics Consortium (INSACOG). The group plans to sequence 5 percent of all positive COVID cases in the country (the current rate is only 0.09 percent). Shahid Jameel, a virologist and director of the Trivedi School of Biosciences at India’s Ashoka University, says that bringing existing surveillance capacity under a single umbrella could, in principle, make that a feasible goal. But there are not enough trained field-workers, he says, and the laboratories have acute shortages of chemical reagents needed for genomic analyses.
International experts are now stepping in to help. Recently, a nonprofit volunteer group called INDIA COVID SOS formed to assist with the pandemic response in the country. It aims to scale genomic surveillance across India, as well among neighboring South Asian nations. Aditi Hazra, an epidemiologist at Harvard Medical School, co-leads the group’s sequencing team, which meets regularly on video conference calls with the directors of India’s sequencing consortium. She says a key objective is to extend viral surveillance to more people in rural areas, where much of the population lives.
Rural surveillance is a priority in Africa as well. Millions of people on the continent live in remote areas that “are also hot spots for disease outbreaks,” says Akaninyene Otu, a medical doctor and a senior lecturer at the University of Calabar in Nigeria. Several new partnerships aim to boost sequencing in African countries. Otu highlights the Africa Pathogen Genomics Initiative (Africa PGI), which launched last year with support from international donor organizations and private companies. Most of the sequencing capacity in Africa is concentrated in South Africa, Kenya, Nigeria, Morocco and Egypt. The Africa PGI, which is headed by the Africa Centers for Disease Control and Prevention, is setting out to create a pan-African network of sequencing centers to serve the continent’s 54 countries.
In Latin American countries—which are currently reporting some of the highest COVID infection rates in the world—PAHO is spearheading the COVID-19 Genomic Surveillance Regional Network. Some countries in the region already have fairly strong sequencing capabilities, but the network is leading efforts to build surveillance capacity where it does not exist at all, which is the case throughout much of Central America. In the interim, two large reference labs—one in Brazil and one in Chile—are sequencing samples sent by other countries “at PAHO's expense,” Mendez-Rico says.
In addition to building partnerships and networks, scientists are also exploring low-cost sequencing technologies that could be deployed easily in the field. Nearly all of the SARS-CoV-2 cases sequenced so far have relied on large, expensive instruments housed in climate-controlled lab facilities. As an alternative, INDIA COVID SOS is encouraging wider use of a handheld sequencing device made by Oxford Nanopore Technologies in England. The device, called the MinION, can run on a battery pack, processes 96 samples at a time and uses software to generate whole genome sequences that can be stored on a laptop. “We're looking for technologies that are cheap, efficient, scalable and portable, and this is an example,” Hazra says.
Keith Robison, a computational biologist at Ginkgo Bioworks, a Boston-based biotechnology company, agrees that the MinION is a practical option for developing nations—especially in rural settings. The portable technology was widely used during the recent Ebola outbreaks in the Democratic Republic of the Congo and other West African countries. “You can generate sequences with it from anywhere,” he says. The MinION has its drawbacks: the quality of the data is not as good as what the lab-based instruments provide, Robison notes. “However, that can also be computationally corrected if you have many copies of the same sequence,” he says.
Tue Sparholt Jørgensen, a postdoctoral researcher in microbiology at the Technical University of Denmark, argues that whole-genome sequences may not always be needed. All the important SARS-CoV-2 mutations identified so far, he says, sit on the same stretch of genome encoding the microbe’s well-known spike protein. Jørgensen says scientists can simply target this piece of the viral geome with an alternative method called Sanger sequencing. This method, which was used as part of the effort that led to the sequencing of the complete human genome back in 2003, is still employed by labs all over the world. Unlike whole-genome methods that sequence millions of genetic fragments simultaneously, the Sanger method sequences one fragment at a time. “Sanger can't replace whole-genome sequencing, but you can use it for targeted analyses at a fraction of the cost,” Jørgensen says. “People have been using it in small labs for decades. I’d use it to monitor for known variants, [to] qualify samples for whole genome sequencing and for contact tracing [of infected people] in hospitals.”
Jørgensen and his colleagues are now working with health officials in Rwanda on plans to expand Sanger-based COVID surveillance in the country. “If a new variant emerges in Rwanda and starts spreading [elsewhere] in Africa, then we want to know about it,” he says.