Genome sequencing reveals the course of COVID-19 in Africa

Africa lagged behind in genome sequencing in the first two years of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, with increasing funding, over 100,000 genomes have now been sequenced from that continent.

A new study summarizes the results of genomic surveillance to date, showing how the virus’ variants of concern have spread, while also showing the future direction for responsiveness.

introduction

Africa appeared relatively spared from high cases and deaths during the ongoing pandemic, with about 11 million cases out of over 600 million total and a quarter of a million deaths out of over 6.4 million deaths worldwide.

However, as the virus continued to evolve and mutate, new variants emerged, in some cases showing higher transmissibility and infectivity or virulence. Immune escape mutations have been identified in some variants, allowing them to spread more frequently among vaccinated or previously infected populations. These have been termed Variants of Concern (VOC) and so far there have been five of them – Alpha, Beta, Gamma, Delta and Omicron.

Of these, Beta and Omicron were first detected in Africa, although the other two also caused significant cases on that continent. In response to the growing threat of exposure to VOCs, samples were collected for sequencing from multiple sites. However, as of April 2020, only 20 African countries had this capability.

As global supply chains dried up, these efforts were halted towards the end of the year. After the first 10,000, an analysis revealed some missing areas, prompting increased funding to build reinforced infrastructure and train staff for genome monitoring.

Both the Africa Centers for Disease Control (Africa CDC) and the WHO Regional Office in Africa (or WHO AFRO) shared responsibility for this, supported by many other individuals and organizations. The result was that from April 2021 to March 2022 another 90,000 sequences were uploaded.

For comparison, fewer than 4,000 human immunodeficiency virus (HIV) and 12,000 influenza sequences have been uploaded to date, despite their presence in Africa in alarming numbers for many years.

The current study, published in Scienceinvestigates the contribution of genome sequencing to the scientific understanding of COVID-19 on this continent and also introduces global public health response through the ability to detect new variants early enough.

What did the study show?

The data show multiple waves of infection, varying in scale and timing from country to country. However, after the first two waves, dominated by B.1 and Alpha variants, Delta and Omicron swept across Africa in dismal succession.

In different parts of Africa, different strains such as C.36 and C.36.3, which caused 40% of infections in Egypt, were dominant over the B.1.160 lineage in Tunisia. In both cases, these gave way to Delta during the third wave.

In South Africa, beta rather than alpha dominated the second wave. Interestingly, although the C.1.2 variant showed signs of immune escape, it failed to produce any appreciable effect against the delta background.

Other lines that competed with Alpha were B.1.525 and A.23.1, which were eventually surpassed by later emerging VOCs. The differences in lineage by region could be due to viral genetics, human mobility, competition between co-circulating lineages, and immunity levels.

Delta caused the biggest impact, according to many analysts, causing over a third of all infections in Africa. Beta causes about one in seven and alpha only about 4% overall. Omicron, which is still spreading, caused over a fifth of all infections, according to genome sequencing.

In contrast to the previous VOCs, Omicron became known against a background of high infection and vaccination rates with high associated immunity levels. Coupled with its lower intrinsic virulence, Omicron has resulted in fewer deaths than other VOCs, consistent with South Africa’s lower mortality rate during this wave.

The first part of the pandemic was caused by strains of the B.1 clade, or ancestral viruses, which were then replaced by the first group of VOCs from late 2020: Alpha, Beta and then, in 2021, Delta and Omicron. While alpha and beta circulated mainly in different regions of Africa, delta and omicron dominated infections in Africa, which began shortly after their emergence.

The data come from combining epidemiological data with genome sequencing data, as well as information on the temporal and magnitude characteristics of these waves. However, some countries have tested just one in ten million residents, while others have tested over 10,000 in ten million, indicating very heterogeneous testing rates.

Interestingly, countries with high testing rates have also reported higher case rates, but undercoverage remains a reality, as in the rest of the world. Increased coverage has largely been achieved through the use of relatively inexpensive sequencing technology.

There is an urgent need to increase sequencing capacity as 16 countries still lack local sequencing facilities while many others have limited capacity. Three world-class sequencing centers and several regional sequencing centers have been established to consolidate resources in a few countries and maximize sequencing across the continent. These centers mainly helped sub-Saharan countries by handling all local sequencing efforts in some countries like Angola and Namibia, but also collaborated with local sequencing efforts during waves.

Other facilities outside of Africa have also been commissioned to increase surveillance, particularly for West and North African countries.

Ultimately, a mix of strategies of local sequencing, shared resource sharing between African countries, and sequencing with academic collaborators outside the continent helped close surveillance blind spots.”

Even at low levels of sequencing, representative sampling over time has helped maintain genomic surveillance and timely detection of variants, including beta and omicron. In addition, the processing time will be gradually reduced from, for example, ~180 days to 50 days from October 2020 to a year later.

This is favored by the use of local sequencing networks over regional or external facilities, suggesting the need to invest in the latter. The travel bans that followed the discovery and reporting of VOCs Beta and Omicron show how countries may be reluctant to report such data in the future. If the sequencing can only be done outside the country, this inevitably leads to a lack of surveillance in such situations.

Therefore, promoting local sequencing capacity will help”Generating timely and regular data for local and regional decision-making.” This would allow emerging variants to be detected early enough to have time to halt their spread.

For example, Beta was discovered three months after its creation, but within five weeks of Omicron. Furthermore, the World Health Organization declared the latter a VOC within 72 hours of depositing its sequence in the database.

Sequencing efforts should be built, not only for SARS-CoV-2, but also for other new or reintroduced pathogens, including Ebola, measles and H1N1 flu. According to the Africa CDC, there are over 200 infectious disease outbreaks on the continent each year.

Beyond the current pandemic, continued investment in diagnostic and sequencing capabilities for these pathogens could serve the continent’s public health well into the 21st century.”