Multiple expansions of globally uncommon SARS-CoV-2 lineages in Nigeria

On February 27, 2020, Nigeria recorded its index case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), and within five months at least one case had been reported in all states across the country. By March 11, 2020, SARS-CoV-2 met the epidemiological landmark of infecting over 100,000 persons in at least 100 countries, and it was consequently declared a pandemic by the World Health Organization (WHO). Building on the success of Nigeria’s response to Ebola, the Nigerian Government immediately activated a national Incident Control Center (ICC) to enable routine surveillance, diagnosis, and prompt reporting of COVID-19 cases. The Nigeria Centre for Disease Control (NCDC) swiftly identified and accredited 70 laboratories (now 84) in all states/regions of the country with human and infrastructural capacity for COVID-19 diagnosis by molecular detection of SARS-CoV-2. Accredited laboratories were supported with basic reagents and consumables for laboratory diagnosis of COVID-19. Subsequently, real-time epidemiological information for routine surveillance of cases across the country was captured in the Surveillance Outbreak Response Management and Analysis System (SORMAS).

Nigeria is the largest black nation with a population of >200 million people, roughly 3.1% of whom are aged 65 years or older and thus at risk of severe COVID-19. A significant proportion of the population has pre-existing, underlying health conditions including diabetes, high blood pressure, cardiovascular diseases, and cancers, that likewise increase their risk for severe COVID-19. Furthermore, Nigeria has a high poverty index (HPI) with an estimated 83 million (40%) of the population living below the poverty line and consequently facing steep disadvantages in healthcare. Given these underlying demographics,  Nigeria’s population also faces a high disease burden from other viral pathogens including Lassa fever, yellow fever, and measles.

Even before the advent of COVID-19, the health care system in Nigeria was relatively weak, plagued by a plethora of challenges. Inadequate infrastructure and limitations in the specialized workforce resulted in a scarcity of healthcare services. With the onset of the COVID-19 pandemic, resources became even more stretched. Due to limited testing capacity, the actual numbers of persons infected could not be ascertained as tests were reserved for symptomatic individuals or those with a known travel history to high-index countries. Quarantine facilities and adequate expertise for timely contact tracing were lacking. Intensive care unit facilities, including ventilators - a requisite for the management of respiratory complications typical of severe COVID-19 cases, were either absent, dilapidated, or obsolete where available, though some upgrades were subsequently made as part of the national response to COVID-19.

Poor healthcare infrastructure and a high population density in major cities, particularly in urban slums and often poorly ventilated homes and offices, make Nigeria a fertile ground for the spread of SARS-CoV-2. Considering that Nigeria is an epicenter of commerce and travel in Africa, we (Ozer et al., 2022) postulated that undetected expansion of a more infectious, virulent, or immune-resistant variant in the region could have major repercussions for the wider region or the entire continent. We additionally noted that a more consistent and higher volume of sample collection was required to strengthen the public health value of COVID-19 genomic surveillance efforts in Nigeria, which NCDC was orchestrating in concert with local institutions such as the African Center of Excellence for Genomics and Infectious Diseases. Thus, amidst several challenges, we set out to identify and longitudinally monitor the circulating variants of SARS-CoV-2 in Nigeria. Samples were collected from the Biorepository and Clinical Virology Laboratory at the College of Medicine, University College Hospital in Ibadan. This laboratory receives samples primarily from Oyo State and other health facilities in the Southwestern region of the country.  

While identifying and collecting positive samples was straightforward, logistics for the transport of these samples was notably more difficult. Significant travel restrictions were in place and airlines continually updated and changed criteria for shipping of biological agents. Courier services and charges increased as airlines became selective in what to transport and how best to transport them. Thus, while laboratories across the country had generated a ton of samples in a short period of time, the country had a limited number of reported SARS-CoV-2 sequences available in public repositories. Thankfully, the Northwestern University Institute for Global Health provided Catalyzer Award funding for sample shipment and sequencing in collaboration with the Center for Pathogen Genomics and Microbial Evolution in Chicago, Illinois, USA. Even with funding, however, sample shipment was challenging as a typical 3-layer biological sample carrier became scarce, and dry ice could only be obtained from Lagos (about 150km from Ibadan). This required us to drive to Lagos to pick up dry ice for each shipment, a trip that could take up to 10 hours due to ongoing road construction at the Lagos-Ibadan freeway. Shipments were thus carefully planned; we set out as early as possible to obtain dry ice from Lagos and return as soon as possible to pack the samples for immediate shipment. The shipment could only take place on specific days; as determined by the airline. As the reviewers requested more and more recent samples, more shipments needed to be coordinated for rapid turnaround with each submission. It was a strenuous experience, but the gains of the study made it worthwhile.

 In our article here (Ozer et al., 2022), we reported sequences from 378 SARS-CoV-2 isolates collected in Oyo State, Nigeria between July 2020 and August 2021. Prior to our submission, Nigeria had a total of only 856 sequences in the GISAID database, with our new samples increasing reporting by nearly 50%. Our results show that in early 2021, most isolates belonged to the B.1.1.7 Alpha ‘variant of concern’ (VOC) or the B.1.525 Eta lineage. Eta outcompeted Alpha in Nigeria and across West Africa, persisting in the region even after the expansion of an otherwise rare Delta sub-lineage. Phylodynamic reconstructions suggest that Eta originated in West Africa before spreading globally. In vitro assays suggest that Eta Spike protein was less susceptible to neutralization by convalescent serum following natural infection,  suggesting that Eta should have been considered a VOC in early 2021 had it not been overlooked due to undersampling in the region. Afterward, we were able to study the uprise of the Delta variant in the country, where once again a very globally uncommon lineage, AY.36, became dominant in the region. This distinct distribution of SARS-CoV-2 lineages in Nigeria emphasizes the need for improved genomic surveillance worldwide and more international partnerships towards the betterment of global health.

 

 References

Akande, Oluwatosin Wuraola et al. “Epidemiological comparison of the first and second waves of the COVID-19 pandemic in Nigeria, February 2020-April 2021.” BMJ global health vol. 6,11 (2021): e007076. doi:10.1136/bmjgh-2021-007076

Al-Mustapha, Ahmad Ibrahim et al. “Nigeria's race to zero COVID-19 cases: True disease burden or testing failure?.” Journal of global health vol. 11 03094. 7 Aug. 2021, doi:10.7189/jogh.11.03094

Nigeria Centre for Disease Control (NCDC). https://covid19.ncdc.gov.ng/laboratory/. Last accessed 29th January 2022