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1. Rapid Replacement of SARS-CoV-2 Variants by Delta and Subsequent Arrival of Omicron, Uganda, 2021

Author

Nicholas Bbosa, Deogratius Ssemwanga, Hamidah Namagembe, Ronald Kiiza, Jocelyn Kiconco, John Kayiwa, Tom Lutalo, Julius Lutwama, Alfred Ssekagiri, Isaac Ssewanyana, Susan Nabadda, Henry Kyobe-Bbosa, Jennifer Giandhari, Sureshnee Pillay, Upasana Ramphal, Yajna Ramphal, Yeshnee Naidoo, Derek Tshiabuila, Houriiyah Tegally, Emmanuel J. San, Eduan Wilkinson, Tulio de Oliveira, and Pontiano Kaleebu

Subjects
coronavirus disease, COVID-19, severe acute respiratory coronavirus 2, SARS-CoV-2, coronaviruses, viruses, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Genomic surveillance in Uganda showed rapid replacement of severe acute respiratory syndrome coronavirus 2 over time by variants, dominated by Delta. However, detection of the more transmissible Omicron variant among travelers and increasing community transmission highlight the need for near–real-time genomic surveillance and adherence to infection control measures to prevent future pandemic waves.

Published
2022
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2. Comparison of SARS-CoV-2 sequencing using the ONT GridION and the Illumina MiSeq

Author

Derek Tshiabuila, Jennifer Giandhari, Sureshnee Pillay, Upasana Ramphal, Yajna Ramphal, Arisha Maharaj, Ugochukwu Jacob Anyaneji, Yeshnee Naidoo, Houriiyah Tegally, Emmanuel James San, Eduan Wilkinson, Richard J. Lessells, and Tulio de Oliveira

Subjects
SARS-CoV-2, Illumina MiSeq, Oxford Nanopore technology GridION, Nanopore sequencing, next generation sequencing, bioinformatics, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Over 4 million SARS-CoV-2 genomes have been sequenced globally in the past 2 years. This has been crucial in elucidating transmission chains within communities, the development of new diagnostic methods, vaccines, and antivirals. Although several sequencing technologies have been employed, Illumina and Oxford Nanopore remain the two most commonly used platforms. The sequence quality between these two platforms warrants a comparison of the genomes produced by the two technologies. Here, we compared the SARS-CoV-2 consensus genomes obtained from the Oxford Nanopore Technology GridION and the Illumina MiSeq for 28 sequencing runs. Results Our results show that the MiSeq had a significantly higher number of consensus genomes classified by Nextclade as good and mediocre compared to the GridION. The MiSeq also had a significantly higher genome coverage and mutation counts than the GridION. Conclusion Due to the low genome coverage, high number of indels, and sensitivity to SARS-CoV-2 viral load noted with the GridION when compared to MiSeq, we can conclude that the MiSeq is more favourable for SARS-CoV-2 genomic surveillance, as successful genomic surveillance is dependent on high quality, near-whole consensus genomes.

Published
2022
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3. Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage

Author

Cathrine Scheepers, Josie Everatt, Daniel G. Amoako, Houriiyah Tegally, Constantinos Kurt Wibmer, Anele Mnguni, Arshad Ismail, Boitshoko Mahlangu, Bronwen E. Lambson, Darren P. Martin, Eduan Wilkinson, James Emmanuel San, Jennifer Giandhari, Nelia Manamela, Noxolo Ntuli, Prudence Kgagudi, Sandile Cele, Simone I. Richardson, Sureshnee Pillay, Thabo Mohale, Upasana Ramphal, Yeshnee Naidoo, Zamantungwa T. Khumalo, Gaurav Kwatra, Glenda Gray, Linda-Gail Bekker, Shabir A. Madhi, Vicky Baillie, Wesley C. Van Voorhis, Florette K. Treurnicht, Marietjie Venter, Koleka Mlisana, Nicole Wolter, Alex Sigal, Carolyn Williamson, Nei-yuan Hsiao, Nokukhanya Msomi, Tongai Maponga, Wolfgang Preiser, Zinhle Makatini, Richard Lessells, Penny L. Moore, Tulio de Oliveira, Anne von Gottberg, and Jinal N. Bhiman

Subjects
Science
Abstract

The SARS-CoV-2 PANGO lineage C.1.2 has been under monitoring by global health authorities as it has spread worldwide. Here, Bhiman and colleagues characterise the emergence of the lineage, and its neutralisation sensitivity using data from vaccinees and previously infected individuals.

Published
2022
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4. SARS-CoV-2 spike protein diversity at an intra-host level, among SARS-CoV-2 infected individuals in South Africa, 2020 to 2022.

Author

Kathleen Subramoney, Nkhensani Mtileni, Ashlyn Davis, Jennifer Giandhari, Houriiyah Tegally, Eduan Wilkinson, Yeshnee Naidoo, Yajna Ramphal, Sureshnee Pillay, Upasana Ramphal, Andiswa Simane, Bhaveshan Reddy, Bonolo Mashishi, Nonhlanhla Mbenenge, Tulio de Oliveira, Burtram C Fielding, and Florette K Treurnicht

Subjects
Medicine, Science
Abstract

Intra-host diversity studies are used to characterise the mutational heterogeneity of SARS-CoV-2 infections in order to understand the impact of virus-host adaptations. This study investigated the frequency and diversity of the spike (S) protein mutations within SARS-CoV-2 infected South African individuals. The study included SARS-CoV-2 respiratory samples, from individuals of all ages, received at the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic hospital, Gauteng, South Africa, from June 2020 to May 2022. Single nucleotide polymorphism (SNP) assays and whole genome sequencing were performed on a random selection of SARS-CoV-2 positive samples. The allele frequency (AF) was determined using TaqMan Genotyper software for SNP PCR analysis and galaxy.eu for analysis of FASTQ reads from sequencing. The SNP assays identified 5.3% (50/948) of Delta cases with heterogeneity at delY144 (4%; 2/50), E484Q (6%; 3/50), N501Y (2%; 1/50) and P681H (88%; 44/50), however only heterogeneity for E484Q and delY144 were confirmed by sequencing. From sequencing we identified 9% (210/2381) of cases with Beta, Delta, Omicron BA.1, BA.2.15, and BA.4 lineages that had heterogeneity in the S protein. Heterogeneity was primarily identified at positions 19 (1.4%) with T19IR (AF 0.2-0.7), 371 (92.3%) with S371FP (AF 0.1-1.0), and 484 (1.9%) with E484AK (0.2-0.7), E484AQ (AF 0.4-0.5) and E484KQ (AF 0.1-0.4). Mutations at heterozygous amino acid positions 19, 371 and 484 are known antibody escape mutations, however the impact of the combination of multiple substitutions identified at the same position is unknown. Therefore, we hypothesise that intra-host SARS-CoV-2 quasispecies with heterogeneity in the S protein facilitate competitive advantage of variants that can completely/partially evade host's natural and vaccine-induced immune responses.

Published
2023
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5. Genomic epidemiology of SARS-CoV-2 during the first four waves in Mozambique.

Author

Nalia Ismael, Stephanie van Wyk, Houriiyah Tegally, Jennifer Giandhari, James Emmanuel San, Monika Moir, Sureshnee Pillay, Christian Utpatel, Lavanya Singh, Yeshnee Naidoo, Upasana Ramphal, Nédio Mabunda, Nuro Abílio, Paulo Arnaldo, Joicymara Xavier, Daniel Gyamfi Amoako, Josie Everatt, Yajna Ramphal, Arisha Maharaj, Leonardo de Araujo, Ugochukwu J Anyaneji, Derek Tshiabuila, Sofia Viegas, Richard Lessells, Susan Engelbrecht, Eduardo Gudo, Ilesh Jani, Stefan Niemann, Eduan Wilkinson, and Túlio de Oliveira

Subjects
Public aspects of medicine, RA1-1270
Abstract

Mozambique reported the first case of coronavirus disease 2019 (COVID-19) in March 2020 and it has since spread to all provinces in the country. To investigate the introductions and spread of SARS-CoV-2 in Mozambique, 1 142 whole genome sequences sampled within Mozambique were phylogenetically analyzed against a globally representative set, reflecting the first 25 months of the epidemic. The epidemic in the country was marked by four waves of infection, the first associated with B.1 ancestral lineages, while the Beta, Delta, and Omicron Variants of Concern (VOCs) were responsible for most infections and deaths during the second, third, and fourth waves. Large-scale viral exchanges occurred during the latter three waves and were largely attributed to southern African origins. Not only did the country remain vulnerable to the introductions of new variants but these variants continued to evolve within the borders of the country. Due to the Mozambican health system already under constraint, and paucity of data in Mozambique, there is a need to continue to strengthen and support genomic surveillance in the country as VOCs and Variants of interests (VOIs) are often reported from the southern African region.

Published
2023
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6. SARS-CoV-2 variants from COVID-19 positive cases in the Free State province, South Africa from July 2020 to December 2021

Author

Peter Mwangi, Javan Okendo, Milton Mogotsi, Ayodeji Ogunbayo, Olusesan Adelabu, Hlengiwe Sondlane, Makgotso Maotoana, Lutfiyya Mahomed, Molefi Daniel Morobadi, Sabeehah Vawda, Anne von Gottberg, Jinal Bhiman, Houriiyah Tegally, Eduan Wilkinson, Jennifer Giandhari, Sureshnee Pillay, Yeshnee Naidoo, Upasana Ramphal, Tulio de Oliveira, Armand Bester, Dominique Goedhals, and Martin Nyaga

Subjects
Beta variant, Delta variant, epidemiological profile, Omicron variant, Free State, SARS-CoV-2 variants, Microbiology, QR1-502
Abstract

Since the COVID-19 outbreak emerged, SARS-CoV-2 has continuously evolved into variants with underlying mutations associated with increased transmissibility, potential escape from neutralizing antibodies, and disease severity. The SARS-CoV-2 pandemic in South Africa has been characterized by periods of infections with four major epidemic waves. To determine whether the variants driving the epidemic waves at the national level were also driving the epidemic waves at the local level, we performed analysis of a total of 1287 samples from qPCR confirmed SARS-CoV-2 positive individuals. The samples were subjected to viral RNA extraction, genomic amplification, and sequencing. Variant assignment of the viral sequences and mutation identification were conducted using PANGOLIN and SARS-CoV-2 genome annotator, respectively. Our analysis revealed that during the initial part of the first wave, B.1, B.1.1, B.1.1.53, B.1.1.448 and B.1.237 circulated in the Free State province, followed by Beta variant, B.1.351 later in the wave. Although most of the initially detected variants disappeared during the second wave, the Beta variant, B.1.351, persisted. Early in the third wave, the Beta variant, B.1.351, predominated but was replaced by the Delta sub-lineage, AY.45. The fourth wave was characterized by unique emergence of the Omicron sub-variant, BA.1. The data further indicates that SARS-CoV-2 variants driving the epidemic waves in the Free State at the local level correlated with the ones driving the epidemic waves at the national level. Findings from this study highlight the importance of continued genomic surveillance and monitoring of the circulating SARS-CoV-2 variants to inform public health efforts and ensure adequate control of the ongoing pandemic.

Published
2022
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7. Correction: Subramoney et al. Molecular Epidemiology of SARS-CoV-2 during Five COVID-19 Waves and the Significance of Low-Frequency Lineages. Viruses 2023, 15, 1194

Author

Kathleen Subramoney, Nkhensani Mtileni, Jennifer Giandhari, Yeshnee Naidoo, Yajna Ramphal, Sureshnee Pillay, Upasana Ramphal, Akhil Maharaj, Derek Tshiabuila, Houriiyah Tegally, Eduan Wilkinson, Tulio de Oliveira, Burtram C. Fielding, and Florette K. Treurnicht

Subjects
n/a, Microbiology, QR1-502
Abstract

In the original publication [...]

Published
2023
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8. Molecular Epidemiology of SARS-CoV-2 during Five COVID-19 Waves and the Significance of Low-Frequency Lineages

Author

Kathleen Subramoney, Nkhensani Mtileni, Jennifer Giandhari, Yeshnee Naidoo, Yajna Ramphal, Sureshnee Pillay, Upasana Ramphal, Akhil Maharaj, Derek Tshiabuila, Houriiyah Tegally, Eduan Wilkinson, Tulio de Oliveira, Burtram C. Fielding, and Florette K. Treurnicht

Subjects
SARS-CoV-2, low frequency, lineages, molecular epidemiology, Microbiology, QR1-502
Abstract

SARS-CoV-2 lineages and variants of concern (VOC) have gained more efficient transmission and immune evasion properties with time. We describe the circulation of VOCs in South Africa and the potential role of low-frequency lineages on the emergence of future lineages. Whole genome sequencing was performed on SARS-CoV-2 samples from South Africa. Sequences were analysed with Nextstrain pangolin tools and Stanford University Coronavirus Antiviral & Resistance Database. In 2020, 24 lineages were detected, with B.1 (3%; 8/278), B.1.1 (16%; 45/278), B.1.1.348 (3%; 8/278), B.1.1.52 (5%; 13/278), C.1 (13%; 37/278) and C.2 (2%; 6/278) circulating during the first wave. Beta emerged late in 2020, dominating the second wave of infection. B.1 and B.1.1 continued to circulate at low frequencies in 2021 and B.1.1 re-emerged in 2022. Beta was outcompeted by Delta in 2021, which was thereafter outcompeted by Omicron sub-lineages during the 4th and 5th waves in 2022. Several significant mutations identified in VOCs were also detected in low-frequency lineages, including S68F (E protein); I82T (M protein); P13L, R203K and G204R/K (N protein); R126S (ORF3a); P323L (RdRp); and N501Y, E484K, D614G, H655Y and N679K (S protein). Low-frequency variants, together with VOCs circulating, may lead to convergence and the emergence of future lineages that may increase transmissibility, infectivity and escape vaccine-induced or natural host immunity.

Published
2023
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9. Deciphering DNA Methylation in HIV Infection

Author

Thilona Arumugam, Upasana Ramphal, Theolan Adimulam, Romona Chinniah, and Veron Ramsuran

Subjects
HIV, epigenetic regulation, DNA methylation, epigenome-wide methylation, epi-therapeutics, Immunologic diseases. Allergy, RC581-607
Abstract

With approximately 38 million people living with HIV/AIDS globally, and a further 1.5 million new global infections per year, it is imperative that we advance our understanding of all factors contributing to HIV infection. While most studies have focused on the influence of host genetic factors on HIV pathogenesis, epigenetic factors are gaining attention. Epigenetics involves alterations in gene expression without altering the DNA sequence. DNA methylation is a critical epigenetic mechanism that influences both viral and host factors. This review has five focal points, which examines (i) fluctuations in the expression of methylation modifying factors upon HIV infection (ii) the effect of DNA methylation on HIV viral genes and (iii) host genome (iv) inferences from other infectious and non-communicable diseases, we provide a list of HIV-associated host genes that are regulated by methylation in other disease models (v) the potential of DNA methylation as an epi-therapeutic strategy and biomarker. DNA methylation has also been shown to serve as a robust therapeutic strategy and precision medicine biomarker against diseases such as cancer and autoimmune conditions. Despite new drugs being discovered for HIV, drug resistance is a problem in high disease burden settings such as Sub-Saharan Africa. Furthermore, genetic therapies that are under investigation are irreversible and may have off target effects. Alternative therapies that are nongenetic are essential. In this review, we discuss the potential role of DNA methylation as a novel therapeutic intervention against HIV.

Published
2021
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10. Molecular Epidemiology and Diversity of SARS-CoV-2 in Ethiopia, 2020–2022

Author

Abay Sisay, Derek Tshiabuila, Stephanie van Wyk, Abraham Tesfaye, Gerald Mboowa, Samuel O. Oyola, Sofonias Kifle Tesema, Cheryl Baxter, Darren Martin, Richard Lessells, Houriiyah Tegally, Monika Moir, Jennifer Giandhari, Sureshnee Pillay, Lavanya Singh, Yajna Ramphal, Arisha Maharaj, Yusasha Pillay, Akhil Maharaj, Yeshnee Naidoo, Upasana Ramphal, Lucious Chabuka, Eduan Wilkinson, Tulio de Oliveira, Adey Feleke Desta, and James E. San

Subjects
Genetics, COVID-19, molecular epidemiology, SARS-CoV-2, whole genome sequence, Ethiopia, Genetics (clinical)
Abstract

Ethiopia is the second most populous country in Africa and the sixth most affected by COVID-19 on the continent. Despite having experienced five infection waves, >499 000 cases, and ∼7 500 COVID-19-related deaths as of January 2023, there is still no detailed genomic epidemiological report on the introduction and spread of SARS-CoV-2 in Ethiopia. In this study, we reconstructed and elucidated the COVID-19 epidemic dynamics. Specifically, we investigated the introduction, local transmission, ongoing evolution, and spread of SARS-CoV-2 during the first four infection waves using 353 high-quality near-whole genomes sampled in Ethiopia. Our results show that whereas viral introductions seeded the first wave, subsequent waves were seeded by local transmission. The B.1.480 lineage emerged in the first wave and notably remained in circulation even after the emergence of the Alpha variant. The B.1.480 was out-competed by the Delta variant. Notably, Ethiopia’s lack of local sequencing capacity was further limited by sporadic, uneven, and insufficient sampling that limited the incorporation of genomic epidemiology in the epidemic public health response in Ethiopia. These results highlight Ethiopia’s role in SARS-CoV-2 dissemination and the urgent need for balanced, near-real-time genomic sequencing.

Published
2023
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11. Comparing SARS-CoV-2 sequencing methodologies during early phase detection of the Delta variant in South Africa

Author

Upasana Ramphal, Derek Tshiabuila, Yajna Ramphal, Jennifer Giandhari, Carel van Heerden, Cheryl Baxter, Stephanie van wyk, Arisha Maharaj, Sureshnee Pillay, Oluwakemi Laguda-Akingba, James Emmanuel San, Eduan Wilkinson, Richard Lessells, and Tulio de Oliveira

Abstract

Background: Genomic surveillance, with the aid of next-generation sequencing (NGS) technologies, revolutionized the SARS-CoV-2 pandemic. Coupled with high-performance analysis software, methodologies such as the Ion Torrent S5 and Illumina MiSeq dramatically improved the genomic surveillance capacity within South Africa during the height of the pandemic. Using de-identified remnant samples collected from Eastern Cape and analysis software, Genome Detective and NextClade, we compared the sequencing process, genomic coverage, quantification of mutations, and clade classification from sequence data generated by these two common “benchtop” NGS platforms. Results: Sequence data analysis revealed success rates of 175/183 (96%) and 172/183 (94%) on the Ion Torrent S5 and Illumina MiSeq, respectively. Internal quality metrics were assessed in terms of genomic coverage (>80%) and the number of mutations identified (Conclusion: The Illumina MiSeq and Ion Torrent S5 are both reliable platforms capable of performing WGS with the use of amplicons and providing specific, accurate, and high throughput analysis of the SARS-CoV-2 whole viral genomes. Both sequencing platforms are feasible platforms for the genomic surveillance of SARS-CoV-2, each with its specific advantages and trade-offs.

Published
2023

12. Impact of intra-host immune adaptations on the evolution of SARS-CoV-2 S protein among individuals with SARS-CoV-2 infections in South Africa, 2020 to 2022

Author

Kathleen Subramoney, Nkhensani Mtileni, Ashlyn Davis, Jennifer Giandhari, Yeshnee Naidoo, Yajna Ramphal, Sureshnee Pillay, Upasana Ramphal, Houriiyah Tegally, Eduan Wilkinson, Andiswa Simane, Bhaveshan Reddy, Bonolo Mashishi, Nonhlanhla Mbenenge, Tulio de Oliveira, Burtram Fielding, and Florette Treurnicht

Abstract

Background Intra-host diversity studies are used to characterise mutational heterogeneity of SARS-CoV-2 infections to understand the impact of virus-host adaptations. This study investigated the frequency and diversity of the spike (S) protein mutations within SARS-CoV-2 infected South African individuals. Methods Single nucleotide polymorphism (SNP) assays and whole genome sequencing were performed on SARS-CoV-2 positive samples. Allele frequency (AF) was determined using TaqMan Genotyper software for SNP analysis and galaxy.eu for analysis of FASTQ reads. Results The SNP assays identified 5.3% (50/948) Delta cases with heterogeneity at delY144 (4%; 2/50), E484Q (6%; 3/50), N501Y (2%; 1/50) and P681H (88%; 44/50). Sequencing identified 9% (210/2381) cases with Beta, Delta, Omicron BA.1, BA.2.15, and BA.4 lineages with heterogeneity in the S protein. Heterogeneity was primarily identified at positions 19 (1.4%) with T19IR (AF 0.2-0.7), 371 (92.3%) with S371FP (AF 0.1-1.0), and 484 (1.9%) with E484AK (0.2-0.7), E484AQ (AF 0.4-0.5) and E484KQ (AF 0.1-0.4). Conclusion Mutations at heterozygous amino acid positions 19, 371 and 484 reduce recognition of neutralising antibodies, however the impact of the multiple substitutions at the same position is unknown. Therefore, we hypothesise that intra-host SARS-CoV-2 quasispecies with heterogeneity in the S protein facilitate competitive advantage of variants that can completely/partially evade host’s natural and vaccine-induced immune responses.

Published
2022

13. Identification of SARS-CoV-2 Omicron variant using spike gene target failure and genotyping assays, Gauteng, South Africa, 2021

Author

Kathleen, Subramoney, Nkhensani, Mtileni, Avani, Bharuthram, Ashlyn, Davis, Beauty, Kalenga, Mikateko, Rikhotso, Mpho, Maphahlele, Jennifer, Giandhari, Yeshnee, Naidoo, Sureshnee, Pillay, Upasana, Ramphal, Yajna, Ramphal, Houriiyah, Tegally, Eduan, Wilkinson, Thabo, Mohale, Arshad, Ismail, Bonolo, Mashishi, Nonhlanhla, Mbenenge, Tulio, de Oliveira, Zinhle, Makatini, Burtram C, Fielding, and Florette K, Treurnicht

Subjects
South Africa, Infectious Diseases, Genotype, SARS-CoV-2, Virology, Spike Glycoprotein, Coronavirus, COVID-19, Humans
Abstract

The circulation of Omicron BA.1 led to the rapid increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases in South Africa in November 2021, which warranted the use of more rapid detection methods. We, therefore, assessed the ability to detect Omicron BA.1 using genotyping assays to identify specific mutations in SARS-CoV-2 positive samples, Gauteng province, South Africa. The TaqPath™ COVID-19 real-time polymerase chain reaction assay was performed on all samples selected to identify spike gene target failure (SGTF). SARS-CoV-2 genotyping assays were used for the detection of del69/70 and K417N mutation. Whole-genome sequencing was performed on a subset of genotyped samples to confirm these findings. Of the positive samples received, 11.0% (175/1589) were randomly selected to assess if SGTF and genotyping assays, that detect del69/70 and K417N mutations, could identify Omicron BA.1. We identified SGTF in 98.9% (173/175) of samples, of which 88.0% (154/175) had both the del69/70 and K417N mutation. The genotyped samples (45.7%; 80/175) that were sequenced confirmed Omicron BA.1 (97.5%; 78/80). Our data show that genotyping for the detection of the del69/70 and K417N coupled with SGTF is efficient to exclude Alpha and Beta variants and rapidly detect Omicron BA.1. However, we still require assays for the detection of unique mutations that will allow for the differentiation between other Omicron sublineages. Therefore, the use of genotyping assays to detect new dominant or emerging lineages of SARS-CoV-2 will be beneficial in limited-resource settings.

Published
2022

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

Author

Raquel Viana, Sikhulile Moyo, Daniel G. Amoako, Houriiyah Tegally, Cathrine Scheepers, Christian L. Althaus, Ugochukwu J. Anyaneji, Phillip A. Bester, Maciej F. Boni, Mohammed Chand, Wonderful T. Choga, Rachel Colquhoun, Michaela Davids, Koen Deforche, Deelan Doolabh, Louis du Plessis, Susan Engelbrecht, Josie Everatt, Jennifer Giandhari, Marta Giovanetti, Diana Hardie, Verity Hill, Nei-Yuan Hsiao, Arash Iranzadeh, Arshad Ismail, Charity Joseph, Rageema Joseph, Legodile Koopile, Sergei L. Kosakovsky Pond, Moritz U. G. Kraemer, Lesego Kuate-Lere, Oluwakemi Laguda-Akingba, Onalethatha Lesetedi-Mafoko, Richard J. Lessells, Shahin Lockman, Alexander G. Lucaci, Arisha Maharaj, Boitshoko Mahlangu, Tongai Maponga, Kamela Mahlakwane, Zinhle Makatini, Gert Marais, Dorcas Maruapula, Kereng Masupu, Mogomotsi Matshaba, Simnikiwe Mayaphi, Nokuzola Mbhele, Mpaphi B. Mbulawa, Adriano Mendes, Koleka Mlisana, Anele Mnguni, Thabo Mohale, Monika Moir, Kgomotso Moruisi, Mosepele Mosepele, Gerald Motsatsi, Modisa S. Motswaledi, Thongbotho Mphoyakgosi, Nokukhanya Msomi, Peter N. Mwangi, Yeshnee Naidoo, Noxolo Ntuli, Martin Nyaga, Lucier Olubayo, Sureshnee Pillay, Botshelo Radibe, Yajna Ramphal, Upasana Ramphal, James E. San, Lesley Scott, Roger Shapiro, Lavanya Singh, Pamela Smith-Lawrence, Wendy Stevens, Amy Strydom, Kathleen Subramoney, Naume Tebeila, Derek Tshiabuila, Joseph Tsui, Stephanie van Wyk, Steven Weaver, Constantinos K. Wibmer, Eduan Wilkinson, Nicole Wolter, Alexander E. Zarebski, Boitumelo Zuze, Dominique Goedhals, Wolfgang Preiser, Florette Treurnicht, Marietje Venter, Carolyn Williamson, Oliver G. Pybus, Jinal Bhiman, Allison Glass, Darren P. Martin, Andrew Rambaut, Simani Gaseitsiwe, Anne von Gottberg, and Tulio de Oliveira

Subjects
Models, Molecular, Recombination, Genetic, Botswana, Multidisciplinary, SARS-CoV-2, COVID-19, 610 Medicine & health, Antibodies, Neutralizing, South Africa, 360 Social problems & social services, Mutation, Spike Glycoprotein, Coronavirus, Humans, Phylogeny, Immune Evasion
Abstract

The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) 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, B.1.1.529) 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, which are 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.

Published
2022

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

Author

Raquel Viana, Sikhulile Moyo, Daniel G Amoako, Houriiyah Tegally, Cathrine Scheepers, Christian L Althaus, Ugochukwu J Anyaneji, Phillip A Bester, Maciej F Boni, Mohammed Chand, Wonderful T Choga, Rachel Colquhoun, Michaela Davids, Koen Deforche, Deelan Doolabh, Susan Engelbrecht, Josie Everatt, Jennifer Giandhari, Marta Giovanetti, Diana Hardie, Verity Hill, Nei-Yuan Hsiao, Arash Iranzadeh, Arshad Ismail, Charity Joseph, Rageema Joseph, Legodile Koopile, Sergei L Kosakovsky Pond, Moritz UG Kraemer, Lesego Kuate-Lere, Oluwakemi Laguda-Akingba, Onalethatha Lesetedi-Mafoko, Richard J Lessells, Shahin Lockman, Alexander G Lucaci, Arisha Maharaj, Boitshoko Mahlangu, Tongai Maponga, Kamela Mahlakwane, Zinhle Makatini, Gert Marais, Dorcas Maruapula, Kereng Masupu, Mogomotsi Matshaba, Simnikiwe Mayaphi, Nokuzola Mbhele, Mpaphi B Mbulawa, Adriano Mendes, Koleka Mlisana, Anele Mnguni, Thabo Mohale, Monika Moir, Kgomotso Moruisi, Mosepele Mosepele, Gerald Motsatsi, Modisa S Motswaledi, Thongbotho Mphoyakgosi, Nokukhanya Msomi, Peter N Mwangi, Yeshnee Naidoo, Noxolo Ntuli, Martin Nyaga, Lucier Olubayo, Sureshnee Pillay, Botshelo Radibe, Yajna Ramphal, Upasana Ramphal, James E San, Lesley Scott, Roger Shapiro, Lavanya Singh, Pamela Smith-Lawrence, Wendy Stevens, Amy Strydom, Kathleen Subramoney, Naume Tebeila, Derek Tshiabuila, Joseph Tsui, Stephanie van Wyk, Steven Weaver, Constantinos K Wibmer, Eduan Wilkinson, Nicole Wolter, Alexander E Zarebski, Boitumelo Zuze, Dominique Goedhals, Wolfgang Preiser, Florette Treurnicht, Marietje Venter, Carolyn Williamson, Oliver G Pybus, Jinal Bhiman, Allison Glass, Darren P Martin, Andrew Rambaut, Simani Gaseitsiwe, Anne von Gottberg, and Tulio de Oliveira

Abstract

SummaryThe 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.

Published
2021

16. Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage

Author

Cathrine Scheepers, Josie Everatt, Daniel G. Amoako, Houriiyah Tegally, Constantinos Kurt Wibmer, Anele Mnguni, Arshad Ismail, Boitshoko Mahlangu, Bronwen E. Lambson, Darren P. Martin, Eduan Wilkinson, James Emmanuel San, Jennifer Giandhari, Nelia Manamela, Noxolo Ntuli, Prudence Kgagudi, Sandile Cele, Simone I. Richardson, Sureshnee Pillay, Thabo Mohale, Upasana Ramphal, Yeshnee Naidoo, Zamantungwa T. Khumalo, Gaurav Kwatra, Glenda Gray, Linda-Gail Bekker, Shabir A. Madhi, Vicky Baillie, Wesley C. Van Voorhis, Florette K. Treurnicht, Marietjie Venter, Koleka Mlisana, Nicole Wolter, Alex Sigal, Carolyn Williamson, Nei-yuan Hsiao, Nokukhanya Msomi, Tongai Maponga, Wolfgang Preiser, Zinhle Makatini, Richard Lessells, Penny L. Moore, Tulio de Oliveira, Anne von Gottberg, and Jinal N. Bhiman

Subjects
Multidisciplinary, Neutralization Tests, SARS-CoV-2, Spike Glycoprotein, Coronavirus, General Physics and Astronomy, COVID-19, Humans, General Chemistry, Antibodies, Viral, Antibodies, Neutralizing, General Biochemistry, Genetics and Molecular Biology
Abstract

Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substitution rate, and includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 variants of concern or variants of interest. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta show high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.

Published
2021

17. Management and containment of a SARS-CoV-2 Beta variant outbreak at the Malawi University of Science and Technology

Author

Gama Bandawe, Richard Luhanga, Joseph Bitilinyu-Bangoh, Address Malata, Maladalitso Kamaliza, Tonney S. Nyirenda, Houriiyah Tegally, Saizi Kimu, Jennifer Giandhari, Mwayiwawo Madanitsa, Yanjanani Nyakanyaka, Mtisunge Mpakati, Yashnee Naidoo, Upasana Ramphal, Bernard Mvula, Eduan Wilkinson, Petros Kingstone Chigwechokha, Tulio de Oliveira, Charles Makamo, Jeverson Mwale, Yohane Kazembe, Precious Kunyenje, Martha Sambani, Sureshnee Pillay, and Emmanuel James San

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Geography, Coronavirus disease 2019 (COVID-19), Routine testing, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Family medicine, education, medicine, Outbreak, Approaches of management, Test (assessment)
Abstract

Outbreaks of COVID at university campuses can spread rapidly and threaten the broader community. We describe the management of an outbreak at a Malawian university in April-May 2021 during Malawi’s second wave. Classes were suspended following detection of infections by routine testing and campus-wide PCR mass testing was conducted. Fifty seven cases were recorded, 55 among students, two among staff. Classes resumed 28 days after suspension following two weeks without cases. Just 6.3% of full-time staff and 87.4% of outsourced staff tested while 65% of students at the main campus and 74% at the extension campus were tested. Final year students had significantly higher positivity and lower testing coverage compared to freshmen. All viruses sequenced were beta variant and at least four separate virus introductions onto campus were observed. These findings are useful for development of campus outbreak responses and indicate the need to emphasize staff, males and senior students in testing.Article Summary LineSuccessful management of a campus outbreak using test trace and isolate approach with resumption within a month following suspension of all in-person classes. Trends in voluntary testing by gender, age and year of study that can help in formation of future management approaches.

Published
2021

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

Author

Aida Elargoubi, John M. Morobe, Jiro Yasuda, Madisa Mine, Faustinos T. Takawira, Jean-Jacques Muyembe Tamfum, Amal Souissi, Hela Karray, Dominique Goedhals, Michael Owusu, Mitoha O. Ayekaba, Pascale Ondoa, Bryan Fulbert Nkengfack Tegomoh, Daniel G. Amoako, Mathabo Mareka, Sameh Trabelsi, Dorcas Maruapula, Magalutcheemee Ramuth, Danny S. Park, Bamidele Soji Oderinde, Maitshwarelo I. Matsheka, Robert A. Kingsley, Philippe Dussart, Matthew Cotten, Hesham A. Elgahzaly, Oyewale Tomori, Arash Iranzadeh, Nicksy Gumede, Marta Giovanetti, Folarin Onikepe, Omoruyi E. Chukwuma, Nnaemeka Ndodo, Mba Nwando, Oladiji Femi, Sylvie L. Budiaki, Gemma L. Kay, Johnson C. Okolie, Saber Masmoudi, Okokhere Peter, Hlanai Gumbo, Sara H.A. Agwa, Mooko Sekhele, Imed Gaaloul, Sheila M. Mandanda, Enatha Mukantwari, Ngonda Saasa, Sanaâ Lemriss, Hellen Nansumba, Akano Kazeem, Upasana Ramphal, Carolyn Williamson, Belinda Louise Herring, Vagner Fonseca, Edidah M. Ong'era, Joana Q. Mends, Ahmed E Ogwell Ouma, Anika Vinze, Ahmad Sayed, Richard Phillips, Adewunmi M. Olubusuyi, Bourema Kouriba, Vivianne Gorova, John O. Gyapong, Tulio de Oliveira, Arnold W. Lambisia, Najla Kharrat, Wolfgang Preiser, Ojide Chiedozie Kingsley, Yenew K. Tebeje, Sherihane Aryeetey, Yaw Bediako, David A. Rasmussen, Wael H. Roshdy, Norosoa Harline Razanajatovo, Siham Elhamoumi, Sylvie van der Werf, Moussa Moïse Diagne, Claudia Daubenberger, Oshomah Cyril, Andrew J. Page, Uwanibe Jessica, Matoke-Muhia Damaris, Daniel J. Bridges, Sumir Panji, Mahjoub Aouni, Adnene Hammami, Simani Gaseitsiwe, Daniel Lule Bugembe, Gugu Maphalala, Kim Hae-Young, Mohamed K. Khalifa, Safietou Sankhe, Fabian H. Leendertz, Richard Njouom, Ousmane Faye, Kwabena O. Duedu, Jeffrey G. Shaffer, Tobias Schindler, Bankole Bolajoko, Cathrine Scheepers, Francisca M. Muyembe, Ajogbasile F. Victoria, Mirabeau T. Youtchou, Ayoade Femi, Amel Chtourou, Kefentse A. Tumedi, Adrienne A. Amuri, Joyce M. Ngoi, Etile Anoh, Richmond Gorman, Mohamed Abouelhoda, Ali Ahmed Yahaya, Paulo Arnaldo, Alexander J. Trotter, Lahcen Belyamani, Isaac Ssewanyana, Susan Nabadda, Arshad Ismail, Julia C. Andeko, James Emmanuel San, Susan Engelbrecht, Sikhulile Moyo, Jinal N. Bhiman, Jean-Michel Heraud, Julius J. Lutwama, Samar Metha, Amadou Diallo, Soa-Fy Andriamandimby, Rosina A. A. Carr, Edgar Simulundu, Steve A. Mundeke, Nelson B. Silochi, Shymaa S. Ahmed, Nadia Touil, Ihekweazu Chikwe, Deogratius Ssemwanga, Ilhem Boutiba-Ben Boubaker, Houriiyah Tegally, Okogbenin Sylvanus, Abdoul K. Sangare, Mulenga Mwenda, Fausta Shakiwa Mosha, Amadou A. Sall, Derek Tshiabuila, D. James Nokes, Yvan Butera, Maximillian Mpina, Adedotun-Sulaiman Kemi, Onwe E. Ogah, Jean B. Lekana-Douk, Stephen F. Schaffner, Vincent Enouf, Chantal Akoua-Koffi, Diarra Bassirou, Edwin Shumba, Deelan Doolabh, Saba Gargouri, Kayode T. Adeyemi, Wonderful T. Choga, Nicola Mulder, Inbal Gazy, Mushal Allam, Saâd El Kabbaj, Christian T. Happi, Frank Tanser, Sobajo Tope, Michael R. Wiley, Katherine J. Siddle, Charles N. Agoti, John Kayiwa, George Githinji, Diego F. Cuadros, Abdoul-Salam Ouédraogo, Fowotade Adeola, Sonia Lekana-Douki, Edith N. Ngabana, William Ampofo, U George, Elmostafa El Fahime, Jean-Claude C Makangara, Nalia Ismael, Ebenezer Foster-Nyarko, Samar K. Kassim, Nedio Mabunda, Hafaliana Christian Ranaivoson, Tapfumanei Mashe, Sylvie Behillil, Etienne Simon-Loriere, Donwilliams O. Omuoyo, Darren P. Martin, Azeddine Ibrahimi, Paul E. Oluniyi, Richard J Lessells, My V. T. Phan, Feriel Bouzid, Salako B. Lawal, Gert U. van Zyl, Fares Wasfi, Christophe Peyrefitte, Joyce Namulondo, Ugochukwu J. Anyaneji, Mariétou Faye Paye, Augustina Sylverken, Sébastien Calvignac-Spencer, Malebogo Kebabonye, Sophie J Prosolek, Mahmoud el Hefnawi, Adeyemi O. O. Oluwapelumi, Fakayode O. Enoch, Eddy Kinganda Lusamaki, Gaetan Thilliez, Beatrice Dhaala, Gabriel K. Mbunsu, Lavanya Singh, Nnennaya A. Ajayi, Justin O'Grady, Olawoye Idowu, Ngoy Nsenga, Baba Marycelin, Ndongo Dia, Abdul Karim Sesay, Ikponmwosa Odia, Chika K. Onwuamah, Pardis C. Sabeti, Collins M. Morang’a, Hajar Lemriss, Dominic S. Y. Amuzu, Jones Gyamfi, Sofonias K. Tessema, Iyaloo Konstantinus, Pontiano Kaleebu, Patrick Semanda, Fawzi Derrar, Alpha Kabinet Keita, Joweria Nakaseegu, Ibtihel Smeti, Jocelyn Kiconco, Audu Rosemary, K Said, Bronwyn Kleinhans, Fatma Abdelmoula, Sureshnee Pillay, Abechi Priscilla, Manel Turki, Fred A. Dratibi, Berthe-Marie Njanpop-Lafourcade, Zaydah R. de Laurent, David Baker, Nadine Rujeni, Oguzie Judith, Peter K. Quashie, Phillip Armand Bester, Emmanuel Lokilo, Catherine Pratt, Nabil Abid, Mamadou Diop, Placide Mbala, Eduan Wilkinson, Johnathan A. Edwards, Ahmed Rebai, Haruka Abe, Ana Victoria Gutierrez, Thanh Le-Viet, Essia Belarbi, Steven Rudder, Jouali Farah, Maha Mastouri, Nei-yuan Hsiao, Happi Anise, Cara E. Brook, Lamia Fki-Berrajah, Gordon A. Awandare, Ugwu Chinedu, Abdel-Rahman N. Zekri, Sami Kammoun, Leonardo de Oliveira Martins, Martin M. Nyaga, Lynn Tyers, Jingjing Li, Ikhlas Ben Ayed, Mouna Ouadghiri, Amadou Koné, Reuben Ayivor-Djanie, Innocent Mudau, Thabo Mohale, Olumade Testimony, Eromon Philomena, Yeshnee Naidoo, Patrice Combe, Seydou Doumbia, Anne von Gottberg, Akpede George, Nosamiefan Iguosadolo, Mohamed G. Seadawy, Bronwyn McInnis, Faida Ajili, Grit Schubert, Tarik Aanniz, Maureen W. Mburu, Soumeya Ouangraoua, John N. Nkengasong, Jennifer Giandhari, University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Stellenbosch University, Laboratório de Biologia Molecular de Flavivírus [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), University of Cincinnati (UC), University of Cape Town, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), University of Chicago, Institut Pasteur de Madagascar, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Centre Hospitalier de Mayotte, Centre Pasteur du Cameroun, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Sfax - University of Sfax, National Institute for Communicable Diseases [Johannesburg] (NICD), University of the Witwatersrand [Johannesburg] (WITS), Centre Hospitalier Universitaire Souro Sanou [Bobo-Dioulasso] (CHUSS), Centre for the AIDS Programme of Research [Durban, South Africa] (CAPRISA), University of Washington [Seattle], The University of Ghana (WACCBIP) team was funded by a Wellcome/African Academy of Sciences Developing Excellence in Leadership Training and Science (DELTAS) grant (DEL-15-007 and 107755/Z/15/Z: Awandare), National Institute of Health Research (NIHR) (17.63.91) grants using UK aid from the UK government for a global health research group for genomic surveillance of malaria in West Africa (Wellcome Sanger Institute, UK) and the global research unit for Tackling Infections to Benefit Africa (TIBA partnership, University of Edinburgh), and a World Bank African Centres of Excellent grant (WACCBIP-NCDs: Awandare). Project ADAGE PRFCOV19-GP2 (2020-2022) includes 40 researchers from the Center of Biotechnology of Sfax, the University of Sfax, the University of Monastir, the University Hospital Hédi Chaker of Sfax, the Military Hospital of Tunis, and Dacima Consulting. Ministry of Higher Education and Scientific Research and Ministry of Health of the Republic of Tunisia. The Uganda contributions were funded by the UK Medical Research Council (MRC/UKRI) and the UK Department for International Development (DFID) under the MRC/DFID concordat agreement (grant agreement number NC_PC_19060) and by the Wellcome, DFID–Wellcome Epidemic Preparedness–Coronavirus (grant agreement number 220977/Z/20/Z) awarded to M.C. Work from Quadram Institute Bioscience was funded by The Biotechnology and Biological Sciences Research Council Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent projects BBS/E/F/000PR10348, BBS/E/F/000PR10349, BBS/E/F/000PR10351, and BBS/E/F/000PR10352 and by the Quadram Institute Bioscience BBSRC–funded Core Capability Grant (project number BB/CCG1860/1). The Africa Pathogen Genomics Initiative (Africa PGI) at the Africa CDC is supported by the Bill & Melinda Gates Foundation (INV018978 and INV018278), Illumina Inc, the US Centers for Disease Control and Prevention (CDC), and Oxford Nanopore Technologies. Sequences generated in Zambia through PATH were funded by the Bill & Melinda Gates Foundation. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. Funding for sequencing in Côte d’Ivoire, Burkina Faso, and part of the sequencing in the DRC was granted by the German Federal Ministry of Education and Research (BMBF). Sequencing efforts from Morocco have been supported by Academie Hassan II of Science and Technology, Morocco. Funding for surveillance, sampling, and testing in Madagasar was provided by the WHO, the CDC (grant U5/IP000812-05), the US Agency for International Development (USAID, cooperation agreement 72068719CA00001), and the Office of the Assistant Secretary for Preparedness and Response in the US Department of Health and Human Services (DHHS, grant number IDSEP190051-01-0200). Funding for sequencing was provided by the Bill & Melinda Gates Foundation (GCE/ID OPP1211841), Chan Zuckerberg Biohub, and the Innovative Genomics Institute at UC Berkeley. The Botswana Harvard AIDS Institute was supported by the following funding: H3ABioNet through funding from the National Institutes of Health Common Fund (U41HG006941)—H3ABioNet is an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) program of the African Academy of Science (AAS), DHHS–NIH–National Institute of Allergy and Infectious Diseases (NIAID) (5K24AI131928-04 and 5K24AI131924-04), Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant DEL-15-0060—the DELTAS Africa Initiative is an independent funding scheme of the AAS’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant 107752/Z/15/Z] and the UK government, and the South African Medical Research Council (SAMRC) and the Department of Technology and Innovation as part of the Network for Genomic Surveillance in South Africa (NGS-SA) and the Stellenbosch University Faculty of Medicine & Health Sciences, Strategic Equipment Fund. D.P.M. is funded by the Wellcome Trust (Wellcome Trust grant 222574/Z/21/Z). Sequencing activities at the NICD were supported by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response, a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the U.S. Centers for Disease Control and Prevention (grant number 5 U01IP001048-05-00), the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978, the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z), the South African Medical Research Council (Reference number SHIPNCD 76756), the UK Department of Health and Social Care, managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. Furthermore, pandemic surveillance in South Africa and Senegal was supported in part through NIH grant U01 AI151698 for the United World Antiviral Research Network (UWARN). Support for pandemic surveillance from the Tulio de Oliveira group to other African countries is funded by the Rockefeller Foundation. Sequencing efforts in the DRC were funded by the Bill & Melinda Gates Foundation under grant INV-018030 awarded to C.B.P. and further supported by funding from the Africa CDC through the ASLM (African Society of Laboratory Medicine) for Accelerating SARS-CoV-2 Genomic Surveillance in Africa. Sequencing efforts in Rwanda were commissioned by the NIHR Global Health Research program (16/136/33) using UK aid from the UK government (funding to E.M. and N.R. through TIBA partnership) and additional funds from the government of Rwanda through RBC/National Reference Laboratory in collaboration with the Belgian Development Agency (ENABEL) for additional genomic sequencing at GIGA Research Institute–Liege/Belgium. The sequencing effort in Equatorial Guinea was supported by a public-private partnership, the Bioko Island Malaria Elimination Project, composed of the government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon EG Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG. Sample collection and typing in Mali were supported by Fondation Merieux–France, and sequence efforts have been supported by the Enable and Enhance Initiative of the German Federal Government’s Security Cooperation against Biological Threats in the G5 Sahel Region. The Nigeria work was made possible by support from Flu Lab and a cohort of generous donors through TED’s Audacious Project, including the ELMA Foundation, MacKenzie Scott, the Skoll Foundation, and Open Philanthropy. Further Nigeria funding came from grants from the NIAID (www.niaid.nih.gov), NIH-H3Africa (https://h3africa.org) (U01HG007480 and U54HG007480), and the World Bank grant (worldbank.org) (ACE IMPACT project) to C.H. Analysis for the Gabon strains was supported by the Science and Technology Research Partnership for Sustainable Development (SATREPS), Japan International Cooperation Agency (JICA), and Japan Agency for Medical Research and Development (AMED) (grant number JP20jm0110013) and a grant from AMED (grant number JP20wm0225003). Sequencing at KEMRI-Wellcome Trust Research Programme site in Kenya was supported by the National Institute for Health Research (NIHR) (project references 17/63/82 and 16/136/33), using UK aid from the UK Government to support global health research, and the UK Foreign, Commonwealth and Development Office and Wellcome Trust (grant# 102975, 220985)., and We acknowledge the authors from the originating laboratories and the submitting laboratories, who generated and shared, via GISAID, the genetic sequence data on which this research is based (table S4). We also acknowledge the contribution of K. Maria from the NGS-SA platform for their contribution toward the sequencing effort in Cape Town, South Africa. Similarly, we thank A. M. Elsaame, S. M. Elsayed, and R. M. Darwish from the Faculty of Medicine Ain Shams Research Institute (MASRI) for their efforts toward sequencing in Egypt. We thank S. Bane, M. Sanogo, D. Diallo, A. Combo Georges Togo, and A. Coulibaly from the University Clinical Research Centre (UCRC) at the University of Sciences, Techniques, and Technologies of Bamako for the contribution they have made toward sequencing efforts in Mali. We acknowledge the contribution of M. Moeti and A. Salam Gueye from the WHO for their contribution toward combating SARS-CoV-2 on the African continent. We further wish to extend acknowledgment to S. Lutucuta and J. Morais from the Angolan Ministry of Health for their continued hard work with regards to SARS-CoV-2 sampling, sequencing, and pandemic response in Angola. From Malawi we wish to acknowledge the work of B. Chilima, B. Mvula, and M. Chitenje from the Malawian Ministry of Health for their work on the COVID-19 response within the country.

Subjects
2019-20 coronavirus outbreak, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary, Early introduction, Coronavirus disease 2019 (COVID-19), Transmission (medicine), SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Genetic Variation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Genomics, Left behind, Geography, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Development economics, Pandemic, Africa, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, QH426, RA, Pandemics
Abstract

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, 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 following 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 breeding ground for new variants.

Published
2021

19. Emergence and phenotypic characterization of C.1.2, a globally detected lineage that rapidly accumulated mutations of concern

Author

James Emmanuel San, Koleka Mlisana, Vicky L Baillie, Richard J Lessells, Tulio de Oliveira, Thabo Mohale, Zamantungwa T. H. Khumalo, Carolyn Williamson, Noxolo Ntuli, Prudence Kgagudi, Wolfgang Preiser, Wesley C. Van Voorhis, Josie Everatt, Shabir A. Madhi, Anele Mnguni, Florette K. Treurnicht, Cathrine Scheepers, Bronwen E. Lambson, Sureshnee Pillay, Nicole Wolter, Linda-Gail Bekker, Nelia P. Manamela, Penny L. Moore, Yeshnee Naidoo, Zinhle Makatini, Daniel G. Amoako, Nokukhanya Msomi, Jennifer Giandhari, Anne von Gottberg, Sandile Cele, Alex Sigal, Marietje Venter, Arshad Ismail, Houriiyah Tegally, Nei-yuan Hsiao, Eduan Wilkinson, Constantinos Kurt Wibmer, Tongai Maponga, Glenda Gray, Jinal N. Bhiman, Boitshoko Mahlangu, Gaurav Kwatra, Simone I. Richardson, Darren P. Martin, and Upasana Ramphal

Subjects
Delta, Lineage (genetic), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Biology, Beta (finance), Vaccine efficacy, Virology, Neutralization, Transmissibility (vibration), Virus
Abstract

Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The emergence of C.1.2, associated with a high substitution rate, includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 VOC/VOIs. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta showed high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.

Published
2021

20. Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection

Author

Jennifer Giandhari, Khadija Khan, Mallory Bernstein, Houriiyah Tegally, Richard J Lessells, Tulio de Oliveira, Eduan Wilkinson, Nithendra Manickchund Nithendra, Bernadett I Gosnell, Sureshnee Pillay, Lavanya Singh, Nokukhanya Msomi, Cele Sandile, Alex Sigal, Koleka Mlisana, Emmanuel James San, Farina Karim, Upasana Ramphal, Mohamed Ys Moosa, and Willem A. Hanekom

Subjects
Whole genome sequencing, Immune system, Host (biology), Mechanism (biology), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), biology.protein, Human immunodeficiency virus (HIV), medicine, Antiretroviral treatment, Biology, Antibody, medicine.disease_cause, Virology
Abstract

SummaryWhile most people effectively clear SARS-CoV-2, there are several reports of prolonged infection in immunosuppressed individuals. Here we present a case of prolonged infection of greater than 6 months with shedding of high titter SARS-CoV-2 in an individual with advanced HIV and antiretroviral treatment failure. Through whole genome sequencing at multiple time-points, we demonstrate the early emergence of the E484K substitution associated with escape from neutralizing antibodies, followed by other escape mutations and the N501Y substitution found in most variants of concern. This provides support to the hypothesis of intra-host evolution as one mechanism for the emergence of SARS-CoV-2 variants with immune evasion properties.

Published
2021

21. Rapid replacement of the Beta variant by the Delta variant in South Africa

Author

Marta Giovanetti, Marietjie Venter, Stephen N.J. Korsman, Derek Tshiabuila, Anele Nguni, Boitshoko Mahlangu, Diana Hardie, Deelan Doolabh, Adriano Mendes, Tulio de Oliveira, Michaela Davis, Florette K. Treurnicht, Lavanya Singh, Koleka Mlisana, Zamantungwa T. H. Khumalo, Gert U. van Zyl, Kruger Marais, Wasim Abdool Karim, Luiz Carlos Junior Alcantara, Tongai Maponga, Carolyn Williamson, Yeshnee Naidoo, Arisha Maharaj, Yajna Ramphal, Richard J Lessells, Sureshnee Pillay, Christian L. Althaus, Josie Everatt, Wolfgang Preiser, Jennifer Giandhari, Nicole Wolter, Rageema Joseph, Noxolo Ntuli, Amy Strydom, Arshad Ismail, Vagner Fonseca, Dominique Goedhals, Houriiyah Tegally, Nei-yuan Hsiao, Daniel G. Amoako, Martin M. Nyaga, Eduan Wilkinson, Thabo Mohale, Phillip Armand Bester, Nokukhanya Msomi, Gert Marais, Simnikiwe H. Mayaphi, Darren P. Martin, Anne von Gottberg, James Emmanuel San, Susan Engelbrecht, Jinal N. Bhiman, Arash Iranzadeh, Upasana Ramphal, Ugochukwu J. Anyaneji, Kathleen Subramoney, Zinhle Makatini, and Cathrine Scheepers

Subjects
Delta, Transmission (mechanics), law, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Biology, Beta (finance), Third wave, Demography, law.invention
Abstract

The Beta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in South Africa in late 2020 and rapidly became the dominant variant, causing over 95% of infections in the country during and after the second epidemic wave. Here we show rapid replacement of the Beta variant by the Delta variant, a highly transmissible variant of concern (VOC) that emerged in India and subsequently spread around the world. The Delta variant was imported to South Africa primarily from India, spread rapidly in large monophyletic clusters to all provinces, and became dominant within three months of introduction. This was associated with a resurgence in community transmission, leading to a third wave which was associated with a high number of deaths. We estimated a growth advantage for the Delta variant in South Africa of 0.089 (95% confidence interval [CI] 0.084-0.093) per day which corresponds to a transmission advantage of 46% (95% CI 44-48) compared to the Beta variant. These data provide additional support for the increased transmissibility of the Delta variant relative to other VOC and highlight how dynamic shifts in the distribution of variants contribute to the ongoing public health threat.

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