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1.
Preprint in English | Other preprints | ID: ppcovidwho-296139

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.

2.
Preprint in English | Other preprints | ID: ppcovidwho-295924

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.

3.
Cell Host Microbe ; 29(11): 1611-1619.e5, 2021 11 10.
Article in English | MEDLINE | ID: covidwho-1466221

ABSTRACT

The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Vaccination , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Female , Humans , Male , Middle Aged , T-Lymphocytes/immunology
5.
Nat Med ; 27(3): 440-446, 2021 03.
Article in English | MEDLINE | ID: covidwho-1319035

ABSTRACT

The first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency index of 90)1. Despite the early response, by November 2020, over 785,000 people in South Africa were infected, which accounted for approximately 50% of all known African infections2. In this study, we analyzed 1,365 near whole genomes and report the identification of 16 new lineages of SARS-CoV-2 isolated between 6 March and 26 August 2020. Most of these lineages have unique mutations that have not been identified elsewhere. We also show that three lineages (B.1.1.54, B.1.1.56 and C.1) spread widely in South Africa during the first wave, comprising ~42% of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, which has 16 nucleotide mutations as compared with the original Wuhan sequence, including one amino acid change on the spike protein, D614G (ref. 3), was the most geographically widespread lineage in South Africa by the end of August 2020. An early South African-specific lineage, B.1.106, which was identified in April 2020 (ref. 4), became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2. Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020 (ref. 5).


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2/genetics , Datasets as Topic , Genome, Viral , Humans , Molecular Typing , Mutation , Pandemics , Phylogeny , Phylogeography , Real-Time Polymerase Chain Reaction , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Sequence Analysis, RNA , South Africa/epidemiology , Whole Genome Sequencing
7.
Nature ; 592(7854): 438-443, 2021 04.
Article in English | MEDLINE | ID: covidwho-1164876

ABSTRACT

Continued uncontrolled transmission of SARS-CoV-2 in many parts of the world is creating conditions for substantial evolutionary changes to the virus1,2. Here we describe a newly arisen lineage of SARS-CoV-2 (designated 501Y.V2; also known as B.1.351 or 20H) that is defined by eight mutations in the spike protein, including three substitutions (K417N, E484K and N501Y) at residues in its receptor-binding domain that may have functional importance3-5. This lineage was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province. This lineage spread rapidly, and became dominant in Eastern Cape, Western Cape and KwaZulu-Natal provinces within weeks. Although the full import of the mutations is yet to be determined, the genomic data-which show rapid expansion and displacement of other lineages in several regions-suggest that this lineage is associated with a selection advantage that most plausibly results from increased transmissibility or immune escape6-8.


Subject(s)
COVID-19/virology , Mutation , Phylogeny , Phylogeography , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , COVID-19/immunology , COVID-19/transmission , DNA Mutational Analysis , Evolution, Molecular , Genetic Fitness , Humans , Immune Evasion , Models, Molecular , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Selection, Genetic , South Africa/epidemiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Time Factors
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