African coronavirus surveillance network provides early warning for world

South Africa’s swift genomic sequencing was instrumental in alerting the world in December to an unusual genome profile present in samples tested for coronavirus. The Network for Genomic Surveillance in South Africa first spotted the mutated variant in sequencing data from Botswana. As the outbreak continues, national laboratories and the Africa Centres for Disease Control and Prevention (Africa CDC) have joined efforts to ramp up Africa’s sequencing response. This larger Africa-wide network for viral sequencing, which was launched by Africa CDC, the World Health Organization and a group of public, private and non-profit organizations in October 2020, has made rapid progress on the continent. The aim is not only to accelerate surveillance for COVID-19, but also to build the infrastructure and the expertise in next-generation sequencing to confront future epidemic threats as well as to tackle endemic diseases, such as AIDS, tuberculosis, malaria and cholera.

The African Pathogen Genomics Initiative includes centers in South Africa, Nigeria, Senegal, Ghana, Kenya, Democratic Republic of the Congo and Uganda. It launched with $100 million in funding and in-kind contributions from Illumina, Oxford Nanopore, the Bill and Melinda Gates Foundation and Microsoft. By the end of 2020, the network had sequenced 4,000 viral genomes, and the figure has now risen to over 70,000, indicating the continent’s rapid progress last year in aggressively scaling up its sequencing capacities to support its public health response and strengthen genomic surveillance.

Tulio De Oliveira, Director of the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP) in Durban and the Centre for Epidemic Response and Innovation in Stellenbosch, describes the continent’s sequencing capacity as important not just for pathogen monitoring, but also for guiding public health decisions, such as vaccine selection. In February 2021, South Africa halted the Oxford University–AstraZeneca vaccine’s rollout as a result of the vaccine’s disappointing results against the Beta (B.1.351) variant of SARS-CoV-2, which was then the main variant in circulation. Without the sequencing capacity, it would not have been possible to identify the major circulating variants of the virus among the population to select a vaccine. “Genomic data formed the basis of South Africa’s decision to use Johnson & Johnson and Pfizer COVID-19 vaccines,” says De Oliveira.

The network has also blazed a trail in ensuring pandemic surveillance goes beyond urban centers into rural areas, and focuses on identifying and monitoring COVID-19 variants as well as standard PCR testing. It has its own network of sequencing laboratories that covers the entire continent and enables specimen collections, even from remote areas that are difficult to access. Of the over 70,000 genomes sequenced by African countries up to 11 January, according to the GSAID, an open-access coronavirus and flu viral database, those from South Africa accounted for nearly 40% of the total.

According to Anne von Gottberg, a clinical microbiologist at the South African National Institute for Communicable Diseases’ Centre for Respiratory Diseases and Meningitis, the Omicron variant was identified because PCR tests exhibited a partial failure to detect SARS-CoV-2. Omicron’s unusually high number of amino acid changes and deletions in its spike (S) protein, particularly in the receptor-binding domain, means that the primers in some PCR manufacturers’ tests simply don’t detect the variant, leading to S gene dropout. Gottberg says that PCR dropout in detection of the S gene, the viral protein responsible for binding to the host receptor angiotensin-converting enzyme 2 (ACE2), concurrent with the detection of other targets in the viral genome (namely, the nucleocapsid (N) gene) required for the establishment of a diagnosis, called attention to a potential anomaly. “It was the S gene dropout that alerted a private laboratory in South Africa that something was different, and they sent us a batch of these to sequence,” she told Nature Biotechnology.

Speed is crucial to genomic surveillance, and timing has improved dramatically since African countries began to track the Omicron variant. Previously, of African countries, Botswana had the fewest median days from collection to deposition (19 days) and Somalia the highest (232 days). Today, in Africa’s best-performing countries, the time between sample collection and sequence sharing can be as little as 6 days or less. Nine African countries, however, have not shared new sequences for over 100 days, and Cabo Verde and Guinea-Bissau have waited more than 200 days before submitting new sequences.

Despite the continent’s shortcomings, Nicksy Gumede-Moeletsi, regional virologist with the WHO regional office for Africa, says Africa’s progress deserves plaudits. “If we look at what it was before the end of 2020, we had a handful of countries and laboratories that were able to produce the sequencing data. Today, the countries that have their own sequencing data are close to 50. So it shows that there is quite a very robust system that has been really initiated by Africa,” she says.

Overall, the continent’s sequencing setup is robust, notes Christian Happi, director of the African Centre of Excellence for Genomics of Infectious Diseases at Redeemer's University in Nigeria, a key member of the continent-wide laboratory network. “What is beautiful about what is happening during this pandemic is the strong cooperation among African countries.” He also remarks that in some countries where sequencing output has been low or non-existent, this has been due to the low number of cases in that area. “You cannot produce genomes from negative cases,” he says.

The goal now for Africa is to contribute 100,000 genomic sequences to the global database by the end of 2022, says John Nkengasong, director of the Africa CDC. Peter van Heusden, a bioinformatician at the South African National Bioinformatics Institute, hopes the next 50,000 will be even faster, as sequencing and analytical capacities increase. He also hopes resources will be spread more equitably across regions.

Aside from the WHO and the Africa CDC, there are several other local and global players that make up the alliance. As well as regional laboratories, they include international players, the non-profit Gates Foundation, biotech companies Illumina and Oxford Nanopore Technologies, information technology company Microsoft, and the US government CDC.

As part of the support, Illumina pledged $20 million over four years to help strengthen sequencing technology for 20 African countries. This in-kind donation includes next-generation sequencing platforms, reagents and training support. Phil Febbo, Illumina’s chief medical officer, says that the urgency presented by the COVID-19 pandemic has also emerged as an opportunity to tackle geographic disparities in access to sequencing. “Those challenges aren't all the same. Each country has [its] own elements of public health where sequencing can improve outcomes for patients and improve efficiencies in health care systems," he adds.

The continent is still not yet where it should be, however. Nkengasong says: “Are we there yet? No. It is our goal that as many African countries as possible should be able to do the sequencing locally and report the data in real time. So, like many other things on the continent, it takes time to build infrastructure and institutions and networks. But again, I'm really amazed to see the speed at which this particular network — the African Pathogen Genomics Initiative — has grown,” he says.

The COVID-19 pandemic has boosted African sequencing capacity, but, Nkengasong adds, it’s essential that capacity also extends beyond COVID-19, to enhance Africa’s response to other diseases. “They can definitely be cross-cutting [and] used in addressing other emerging infectious diseases or existing ones across the continent,” Nkengasong concludes.