One of the fundamental principles presented by the ancient Chinese military strategist Sun Tzu for victory in battle was to “know your enemy.” Thus, a major tool in the war chest of the modern virus fighter is genomic surveillance (GS), which allows scientists to decode the nature, evolution, and even the virulence of pathogens such as COVID-19.
To be more precise, GS is consistent, coordinated genome sequencing of positive samples at multiple sites within a country or region. During the current pandemic, genomic sequencing was used to identify the nature of SARS-CoV-2, the microbe that causes COVID-19, and trace its relationship to other coronavirus species. It also helped to detect and track the UK, South African, and other variants of the virus that struck deep in the pandemic.
Besides virus identification, GS helps in vaccine development by speeding up the mapping of the genomic structure of infectious agents. Thanks to GS, there are up to 150 vaccine candidates today that target COVID-19 in varying ways. To make nations and regions resilient to pandemics, GS is one of the most important tools to deploy.
How Africa Was Prepared
The African Center of Excellence for Genomics of Infectious Diseases (ACEGID) at Redeemer's University in Ede, Nigeria, is one of two so-called reference centers for the World Health Organization and for all of Africa. ACEGID is funded by the World Bank. The other reference center is the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), located in Durban, South Africa.
At ACEGID, scientists have researched the various pandemics and epidemics that have pummeled Africa in recent decades. Over these difficult years, they have addressed Ebola and Lassa fever, monkeypox, and yellow fever, to name a few. Without a doubt, the continent’s bitter experience with these diseases prepared and shaped its response to COVID-19.
So far, Africa has managed to get through the pandemic more successfully than many other regions of the world—which is actually not surprising. To put the situation in perspective, there have been over 4 million cases now for the entire continent, with over 105,000 deaths (as of April 2021), a remarkably low case rate and death rate. One might ask, then, “How did Africa manage this pandemic so well compared to the rest of the world?”
The reason is simple. African public health authorities have managed several epidemics in the past and have learned a lot, especially from the Ebola outbreak in West Africa from 2014 to 2016 that killed about 11,000 people. In the aftermath of that deadly outbreak, the African heads of state wisely created the Africa Centers for Disease Control. This institution, under the auspices of the African Union, chose integrated genomics as a tool for disease surveillance in Africa. To make that happen, African officials, together with various international groups, set up the Africa Pathogen Genomics Initiative (PGI), which has a mandate to integrate genomics in disease surveillance for the continent. This network was up and running before COVID-19 struck Africa.
The Africa PGI is built around centers of excellence and research hubs on the continent. It leverages national and regional laboratories all across Africa. There are also two continental centers of excellence, namely ACEGID and KRISP. As continental reference centers, they have the mandate to support the national and regional laboratories, build the latter’s capacity, and support African countries that do not have genomics facilities to help them sequence pathogen samples.
The ACEGID sequencing network has five major tasks: 1) mobilize resources, 2) establish routine surveillance, 3) support sample collection and shipment, 4) support sequencing, and 5) support data analysis. To do this important work, the Center has built a strong, coordinated organization capable of leveraging its existing capacity and providing access to sequencing facilities other countries do not have.
COVID-19 in Africa: The First Wave
From very early on, ACEGID employed robotics to assist with analyses for other diseases. The Center had platforms in place like the NovaSeq 6000 system, which can output over six thousand viral sequences in a week. Thus, when the first case of COVID-19 hit sub-Saharan Africa, ACEGID quickly responded. The Ede laboratory became the first in Africa to perform genome sequencing for SARS-CoV-2. It did so within forty-eight hours—a speed no other country in the world has ever matched. That important feat established clearly where the virus came from. The first patient was from Italy and was infected with a viral sample that was very close to the one that was circulating in Switzerland.
The Center went on from there to do additional sequencing on the continent, not only to identify the initial cases of infection and to demonstrate that these cases were imported, but to identify localized spread or transmission.
In Nigeria, after ACEGID identified and sequenced the earliest cases, the government set up a lockdown. From there, the Center started to identify community transmission. This demonstrates how such information has been used to guide policies in many African countries.
Using genomic sequencing across the continent, the Center has been able to show that there were over fifteen hundred introductions of the virus to Africa, most coming from Europe, Asia, Oceania, and the United States. Europe tops the list, likely because of its geographical proximity, and because there is a lot of business and commerce between Europe and Africa.
South Africa has established a GS network within the country, where authorities are able to monitor the situation almost in real time. ACEGID has done the same in Nigeria, where it monitors and tracks the hotspots as well as where the transmission is low. This information is used to guide the government’s understanding of where the hotspots are and to inform public health interventions in the country.
To make public health intervention better focused, two things are needed: 1) speed of execution and 2) accuracy of execution. This is exactly what has been accomplished in Africa over the past few years. There continues to be SARS-CoV-2 sequencing information coming out of Africa, data that are being produced across countries. As most African countries are coming on board, they are generating more data as time goes on.
Africa’s Pandemic Dashboard
ACEGID has created a dashboard that helps the Nigerian Center for Disease Control to see how the pandemic is evolving in real time. Through the dashboard, we can identify the hotspots, and then the government can see how the cases are spreading. We know that in Nigeria alone there were fifty-five different lineages of the disease circulating, with the situation changing fast. Through the use of this interactive dashboard, we have been able to map and track thousands of lineages.
In the case of South Africa, their dashboard showed how the famous B.1.351, or South African variant, began to take over. The ability to monitor that development shows the firepower behind genomic epidemiology. Here you had a case where a new lineage of concern was taking over, a lineage that could have had the ability to escape a vaccine. This is a clear example of how genomic epidemiology has been used on the African continent.
Africa’s very first lineage of concern, or its first variant, was identified as the D614G mutation, which is associated with increased transmissibility of the disease. ACEGID was one of the first groups to describe it and has been monitoring its spread over time. In the case of Nigeria, 90% of the variants have this mutation, which is not peculiar to that country. In South Africa, for example, the number of variants with this mutation is almost 100%.
We also use genomic epidemiology to examine the disease in terms of diagnostics. In terms of molecular diagnostics, if we look, for instance, at the Chinese Center for Disease Control and Prevention primer (the nucleic acid used in DNA synthesis), we see that almost 60% of the circulating virus has a mutation in the area where the primers are supposed to bind. This tells us that those primers may not be reliable for diagnostic purposes. You can see this clearly across other primers, such as those from the Pasteur Institute, the US Centers for Disease Control and Prevention, and the Charité (Berlin). So, when asked to monitor the virus, we have evidence as to whether the assay (analysis) may or may not work for that primer.
The Second Wave: Tracking Down Variants
Africa did pretty well in managing the first wave. But around November and December 2020, we started to see a spike or surge across all of Africa. ACEGID analyzed and tested to discover what the reasons were. The spike in South Africa, for instance, may have been due to the occurrence of a new variant of concern (501Y.V2). There were many mutations associated with that one. The latter may be responsible for the surge that we see not only in South Africa but in many other African countries. ACEGID tracks these variants together with its continental partners.
In the case of Mozambique, for instance, the Kwazulu-Natal Research Institute, a partner in South Africa, established that this variant was introduced to Mozambique twelve times from South Africa. ACEGID was able to identify three clusters of localized transmission as well. It was demonstrated that all the mutations identified from this variant, B.1.351, have affected the transmission and spread of the disease in Mozambique. Samples from Mozambique were sent to South Africa. Then South Africa did its analysis and sent the results back to Mozambique. This is what is done within our network.
In the case of the surge in Nigeria, ACEGID detected a B.1.1.7 lineage, which is a UK variant of concern. The surge in Nigeria was due to this lineage spreading across the country.
Apart from identifying this lineage, what was especially interesting to learn was that the age group affected is very different from the other lineages. The largest number affected by this lineage are people between thirty-one and fifty years of age, followed by those in the age group of thirty years and younger. This is a group of working-age victims, which suggests they are exposed to the virus on the job.
In the process, we identified a new variant, the B.1.525, which emerged from Nigeria and spread across the rest of the world. It is one of the leading variants in the UK, along with B.1.1.7. This variant has not been described as a variant of concern but is now characterized as a variant of interest, because it has the E484K mutation, which has been involved in immune escape. Immune escape means that it has the ability to evade targeting by vaccines and to avoid neutralizing by antibodies.
In conclusion, we have been able to use GS as a critical component of the epidemic response. In the case of Africa, we were able to identify multiple lineages, both new and old. We identified two major lineages in Africa, which are the 501Y.V2 from South Africa and the B.1.525 from Nigeria, both of which have the ability to decrease neutralizing antibody efficacy and to diminish the effectiveness of certain new vaccines.
All told, we in Africa have been able to effectively use genomic epidemiology as a way to respond to this COVID-19 outbreak, guide public health agencies, and provide information critical to Africa’s response to the pandemic.
Editor’s Note: This article is based on a presentation by Dr. Happi at the Twenty-Seventh International Conference on the Unity of the Sciences held in April 2021.
*Christian Happi is a Professor of Molecular Biology and Genomics at Redeemer University, the Director of the African Center of Excellence for Genomics of Infectious Diseases (ACEGID), and Director of the Directorate of Research Innovations and Partnerships (DRIPs).