Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

Three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern predominantly drove South Africa's fourth COVID-19 wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild type amino acid at Q493.The two lineages only differ outside of the spike region. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature . BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.08 - 0.09) and 0.10 (95% CI: 0.09 - 0.11) per day respectively over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus

Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants, respectively1-3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Prevalence of Vitamin D deficiency in a multiracial female population in KwaZulu-Natal province, South Africa

Objective: Vitamin D deficiency is a global health issue affecting many countries, especially those in temperate climates. The aim of this study was to determine the prevalence of Vitamin D deficiency and level of 25-hydroxyvitamin D [25(OH)D] in females categorised by age and race.Methods: The study was performed between January 2015 and January 2016. This study consisted of 1 976 females stratified by age into 18, reproductive age (18–45) and 45 years. Demographic variables were recorded and serum 25(OH)D levels measured by chemiluminescent emission.Results: The predictors of lower 25(OH)D levels included age and race, (p 0.0001 for each predictor). Approximately 46% of females had 20 ng/ml 25(OH)D level, the majority of whom were Indian (35%). The 25(OH)D level varied by race (White 27.33 ng/ml; Black 23.43 ng/ml and Indian 15.05 ng/ml; p 0.0001). In the 18-year age category, White and Black women had significantly higher 25(OH)D levels when compared with Indian women (38.25 ng/ml vs. 37.51 ng/ml vs. 13.68 ng/ml respectively; p 0.0001). Similarly, in the reproductive age category (18–45 years); White (27.63 ng/ml) and Black (20.93 ng/ml) women had a significantly higher 25(OH)D level compared with Indian (13.15 ng/ml) women (p 0.0001). Moreover, similar data were observed within the 45-year age category, where the White and Black women had higher 25(OH)D levels compared with Indian women (25.46 ng/ml vs. 22.73 ng/ml vs. 17.04 ng/ml; p 0.0001) respectively. Irrespective of age category, severe vitamin D deficiency was highest amongst Indian females.Conclusion: This study demonstrates a significant difference in 25(OH)D concentration in healthy females living in Durban, with Indians presenting with the highest vitamin D deficiency. These findings clearly highlight the need for a policy on vitamin D supplementation and/or fortification of food. Further studies are under way to assess the genetic predisposition of women to vitamin D deficiency

Polymorphisms within vitamin D binding protein gene within a Preeclamptic South African population

Objectives: The vitamin D binding protein encoded by the GC gene contains two single nucleotide polymorphisms (rs4588 and rs7041) that have been associated with disease outcome, these include periodontitis coronary heart disease and hypertension. In pregnancy, these SNPs influence vitamin D metabolism that could result in hypertensive disorders such as PE. The etiology of PE, still remains elusive. The aim of this study was to evaluate the distribution of rs4588 and rs7041 within the GC gene among PE and normotensive pregnant women, residing in Durban, KwaZulu-Natal, South Africa. Study design: Our study consisted of n = 600 participants (normotensive (n = 246, N); early onset PE (n = 167, EOPE); and late-onset PE (n = 246, LOPE)). We extracted DNA from whole blood and genotyped for rs4588 and rs7041 SNPs using the TaqMan assay. Results: Regardless of HIV status, we observed the rs4588 (CC genotype) more frequently in PE (EOPE+LOPE) compared to the normotensive participants with an OD ratio of 0.74 (95% CI, 0.35–1.5; p < 0.001). We report a significant difference in the frequency of rs7041 (GT genotype) in the EOPE group compared to the normotensive group with an OD ratio of 11.48 (95% CI, 2.6–103.7; p < 0.001). The rs7041 GT genotype had a higher frequency in the EOPE compared to the LOPE group, with an OD ratio of 15.15 (95% CI, 2.3–639.2; p < 0.001). Conclusion: This is the first study to describe the prevalence of SNPs of the rs4588 and rs7041 within the GC gene in women with PE within the high HIV endemic area of KZN, South Africa. Notably, a significant association of the rs7041 (TT genotype) and rs4588 (CC genotype) occurred at a higher frequency in PE compared to the normotensive cohort. Future studies will examine the functional effect of the GC region in relation to pregnancy and vitamin D deficiency

Evaluation of miniaturized Illumina DNA preparation protocols for SARS-CoV-2 whole genome sequencing.

The global pandemic caused by SARS-CoV-2 has increased the demand for scalable sequencing and diagnostic methods, especially for genomic surveillance. Although next-generation sequencing has enabled large-scale genomic surveillance, the ability to sequence SARS-CoV-2 in some settings has been limited by the cost of sequencing kits and the time-consuming preparations of sequencing libraries. We compared the sequencing outcomes, cost and turn-around times obtained using the standard Illumina DNA Prep kit protocol to three modified protocols with fewer clean-up steps and different reagent volumes (full volume, half volume, one-tenth volume). We processed a single run of 47 samples under each protocol and compared the yield and mean sequence coverage. The sequencing success rate and quality for the four different reactions were as follows: the full reaction was 98.2%, the one-tenth reaction was 98.0%, the full rapid reaction was 97.5% and the half-reaction, was 97.1%. As a result, uniformity of sequence quality indicated that libraries were not affected by the change in protocol. The cost of sequencing was reduced approximately seven-fold and the time taken to prepare the library was reduced from 6.5 hours to 3 hours. The sequencing results obtained using the miniaturised volumes showed comparability to the results obtained using full volumes as described by the manufacturer. The adaptation of the protocol represents a lower-cost, streamlined approach for SARS-CoV-2 sequencing, which can be used to produce genomic data quickly and more affordably, especially in resource-constrained settings

Evaluation of miniaturized Illumina DNA preparation protocols for SARS-CoV-2 whole genome sequencing

The global pandemic caused by SARS-CoV-2 has increased the demand for scalable sequencing and diagnostic methods, especially for genomic surveillance. Although next-generation sequencing has enabled large-scale genomic surveillance, the ability to sequence SARS-CoV-2 in some settings has been limited by the cost of sequencing kits and the time-consuming preparations of sequencing libraries. We compared the sequencing outcomes, cost and turn-around times obtained using the standard Illumina DNA Prep kit protocol to three modified protocols with fewer clean-up steps and different reagent volumes (full volume, half volume, one-tenth volume). We processed a single run of 47 samples under each protocol and compared the yield and mean sequence coverage. The sequencing success rate and quality for the four different reactions were as follows: the full reaction was 98.2%, the one-tenth reaction was 98.0%, the full rapid reaction was 97.5% and the half-reaction, was 97.1%. As a result, uniformity of sequence quality indicated that libraries were not affected by the change in protocol. The cost of sequencing was reduced approximately seven-fold and the time taken to prepare the library was reduced from 6.5 hours to 3 hours. The sequencing results obtained using the miniaturised volumes showed comparability to the results obtained using full volumes as described by the manufacturer. The adaptation of the protocol represents a lower-cost, streamlined approach for SARS-CoV-2 sequencing, which can be used to produce genomic data quickly and more affordably, especially in resource-constrained settings