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1.
Int J Infect Dis ; 118: 150-154, 2022 May.
Article in English | MEDLINE | ID: covidwho-1838855

ABSTRACT

BACKGROUND: At present, it is unclear whether the extent of reduced risk of severe disease seen with SARS-Cov-2 Omicron variant infection is caused by a decrease in variant virulence or by higher levels of population immunity. METHODS: RdRp target delay (RTD) in the Seegene AllplexTM 2019-nCoV PCR assay is a proxy marker for the Delta variant. The absence of this proxy marker in the transition period was used to identify suspected Omicron infections. Cox regression was performed for the outcome of hospital admission in those who tested positive for SARS-CoV-2 on the Seegene AllplexTM assay from November 1 to December 14, 2021 in the Western Cape Province, South Africa, in the public sector. Adjustments were made for vaccination status and prior diagnosis of infection. RESULTS: A total of 150 cases with RTD and 1486 cases without RTD were included. Cases without RTD had a lower hazard of admission (adjusted hazard ratio [aHR], 0.56; 95% confidence interval [CI], 0.34-0.91). Complete vaccination was protective against admission, with an aHR of 0.45 (95% CI, 0.26-0.77). CONCLUSION: Omicron has resulted in a lower risk of hospital admission compared with contemporaneous Delta infection, when using the proxy marker of RTD. Under-ascertainment of reinfections with an immune escape variant remains a challenge to accurately assessing variant virulence.


Subject(s)
COVID-19 , Hepatitis D , COVID-19/diagnosis , Humans , Polymerase Chain Reaction , RNA-Dependent RNA Polymerase , SARS-CoV-2/genetics , South Africa/epidemiology , Survival Analysis
2.
J Clin Virol ; 152: 105170, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1814679

ABSTRACT

BACKGROUND: The Omicron variant of concern is characterised by more than 50 distinct mutations, most in the spike protein. The implications of these for disease transmission, tissue tropism and diagnostic testing needs study. OBJECTIVES: We evaluated the performance of RT-PCR on saliva (SA) swabs and antigen testing on mid-turbinate MT samples relative to RT-PCR on MT swabs. Patients (n = 453) presenting for outpatient testing at the Groote Schuur Hospital COVID-19 testing centre in Cape Town South Africa were recruited. Participants were recruited during the Delta (n = 304) and Omicron (n = 149) waves. RESULTS: In 30 confirmed Delta infections, positive percent agreement (PPA) of RT-PCR on saliva was only 73% compared to a composite standard of either MT or SA RT-PCR positivity, with rapid decay by day 3 after symptom onset. In contrast, in the 70 Omicron infections, SA performed as well as, or better than, MT samples up to day 5, with an overall PPA of SA swabs of 96% and MT of 93%. A change in antigen test performance was noted, with PPA of 93% in Delta, but only 68% for Omicron. CONCLUSIONS: Altered shedding kinetics appear to be present in Omicron-infected patients with more viral RNA detectable in saliva. Saliva swabs are a promising alternative to nasal samples, especially early in infection when sampling of both sites could improve detection. Lower sensitivity of antigen tests in Omicron is a concern and requires further study.


Subject(s)
COVID-19 Testing , COVID-19 , Humans , SARS-CoV-2 , Sensitivity and Specificity , South Africa , Tropism
3.
Tegally, Houriiyah, San, James, Cotten, Matthew, Tegomoh, Bryan, Mboowa, Gerald, Martin, Darren, Baxter, Cheryl, Moir, Monika, Lambisia, Arnold, Diallo, Amadou, Amoako, Daniel, Diagne, Moussa, Sisay, Abay, Zekri, Abdel-Rahman, Barakat, Abdelhamid, Gueye, Abdou Salam, Sangare, Abdoul, Ouedraogo, Abdoul-Salam, Sow, Abdourahmane, Musa, Abdualmoniem, Sesay, Abdul, Lagare, Adamou, Kemi, Adedotun-Sulaiman, Abar, Aden Elmi, Johnson, Adeniji, Fowotade, Adeola, Olubusuyi, Adewumi, Oluwapelumi, Adeyemi, Amuri, Adrienne, Juru, Agnes, Ramadan, Ahmad Mabrouk, Kandeil, Ahmed, Mostafa, Ahmed, Rebai, Ahmed, Sayed, Ahmed, Kazeem, Akano, Balde, Aladje, Christoffels, Alan, Trotter, Alexander, Campbell, Allan, Keita, Alpha Kabinet, Kone, Amadou, Bouzid, Amal, Souissi, Amal, Agweyu, Ambrose, Gutierrez, Ana, Page, Andrew, Yadouleton, Anges, Vinze, Anika, Happi, Anise, Chouikha, Anissa, Iranzadeh, Arash, Maharaj, Arisha, Batchi-Bouyou, Armel Landry, Ismail, Arshad, Sylverken, Augustina, Goba, Augustine, Femi, Ayoade, Sijuwola, Ayotunde Elijah, Ibrahimi, Azeddine, Marycelin, Baba, Salako, Babatunde Lawal, Oderinde, Bamidele, Bolajoko, Bankole, Dhaala, Beatrice, Herring, Belinda, Tsofa, Benjamin, Mvula, Bernard, Njanpop-Lafourcade, Berthe-Marie, Marondera, Blessing, Khaireh, Bouh Abdi, Kouriba, Bourema, Adu, Bright, Pool, Brigitte, McInnis, Bronwyn, Brook, Cara, Williamson, Carolyn, Anscombe, Catherine, Pratt, Catherine, Scheepers, Cathrine, Akoua-Koffi, Chantal, Agoti, Charles, Loucoubar, Cheikh, Onwuamah, Chika Kingsley, Ihekweazu, Chikwe, Malaka, Christian Noël, Peyrefitte, Christophe, Omoruyi, Chukwuma Ewean, Rafaï, Clotaire Donatien, Morang’a, Collins, Nokes, James, Lule, Daniel Bugembe, Bridges, Daniel, Mukadi-Bamuleka, Daniel, Park, Danny, Baker, David, Doolabh, Deelan, Ssemwanga, Deogratius, Tshiabuila, Derek, Bassirou, Diarra, Amuzu, Dominic S. Y.; Goedhals, Dominique, Grant, Donald, Omuoyo, Donwilliams, Maruapula, Dorcas, Wanjohi, Dorcas Waruguru, Foster-Nyarko, Ebenezer, Lusamaki, Eddy, Simulundu, Edgar, Ong’era, Edidah, Ngabana, Edith, Abworo, Edward, Otieno, Edward, Shumba, Edwin, Barasa, Edwine, Ahmed, El Bara, Kampira, Elizabeth, Fahime, Elmostafa El, Lokilo, Emmanuel, Mukantwari, Enatha, Cyril, Erameh, Philomena, Eromon, Belarbi, Essia, Simon-Loriere, Etienne, Anoh, Etilé, Leendertz, Fabian, Taweh, Fahn, Wasfi, Fares, Abdelmoula, Fatma, Takawira, Faustinos, Derrar, Fawzi, Ajogbasile, Fehintola, Treurnicht, Florette, Onikepe, Folarin, Ntoumi, Francine, Muyembe, Francisca, Ngiambudulu, Francisco, Zongo Ragomzingba, Frank Edgard, Dratibi, Fred Athanasius, Iyanu, Fred-Akintunwa, Mbunsu, Gabriel, Thilliez, Gaetan, Kay, Gemma, Akpede, George, George, Uwem, van Zyl, Gert, Awandare, Gordon, Schubert, Grit, Maphalala, Gugu, Ranaivoson, Hafaliana, Lemriss, Hajar, Omunakwe, Hannah, Onywera, Harris, Abe, Haruka, Karray, Hela, Nansumba, Hellen, Triki, Henda, Adje Kadjo, Herve Albéric, Elgahzaly, Hesham, Gumbo, Hlanai, mathieu, Hota, Kavunga-Membo, Hugo, Smeti, Ibtihel, Olawoye, Idowu, Adetifa, Ifedayo, Odia, Ikponmwosa, Boubaker, Ilhem Boutiba-Ben, Ssewanyana, Isaac, Wurie, Isatta, Konstantinus, Iyaloo, Afiwa Halatoko, Jacqueline Wemboo, Ayei, James, Sonoo, Janaki, Lekana-Douki, Jean Bernard, Makangara, Jean-Claude, Tamfum, Jean-Jacques, Heraud, Jean-Michel, Shaffer, Jeffrey, Giandhari, Jennifer, Musyoki, Jennifer, Uwanibe, Jessica, Bhiman, Jinal, Yasuda, Jiro, Morais, Joana, Mends, Joana, Kiconco, Jocelyn, Sandi, John Demby, Huddleston, John, Odoom, John Kofi, Morobe, John, Gyapong, John, Kayiwa, John, Okolie, Johnson, Xavier, Joicymara Santos, Gyamfi, Jones, Kofi Bonney, Joseph Humphrey, Nyandwi, Joseph, Everatt, Josie, Farah, Jouali, Nakaseegu, Joweria, Ngoi, Joyce, Namulondo, Joyce, Oguzie, Judith, Andeko, Julia, Lutwama, Julius, O’Grady, Justin, Siddle, Katherine, Victoir, Kathleen, Adeyemi, Kayode, Tumedi, Kefentse, Carvalho, Kevin Sanders, Mohammed, Khadija Said, Musonda, Kunda, Duedu, Kwabena, Belyamani, Lahcen, Fki-Berrajah, Lamia, Singh, Lavanya, Biscornet, Leon, Le.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334191

ABSTRACT

Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks. One-Sentence Summary Expanding Africa SARS-CoV-2 sequencing capacity in a fast evolving pandemic.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329489

ABSTRACT

In this paper we report on genome sequencing of 154 SARS-CoV-2 samples between June and July 2021 (Summer outbreak) in the Bailiwick of Jersey, a UK channel island. We have analysed extensive data collected on 598,155 RT-qPCR tests that identified 8,950 positive cases as part of public health surveillance from September 2020 to August 2021. Our study implemented an amplicon-based sequencing approach using the Oxford Nanopore Technology (ONT) portable device. This revealed the emergence of twelve AY sublineages and were clustered into the Delta sub-clades 21I and 21J. This was integrated alongside an existing RT-qPCR diagnostic laboratory to provide a sample-to-sequence turnaround time of approximately 30 hours with significant scope for optimisation. Owing to the geographic remoteness of the island from large scale sequencing infrastructure, this presents an opportunity to provide policy makers with near real-time sequencing findings. Our analysis suggests that age and sex remained a substantial risk factor for mortality. We observe viral loads are higher in advanced ages and unvaccinated individuals. The median age of SARS-CoV-2 positive individuals was higher during winter than the summer outbreak, and the contact tracing program showed that younger individuals stayed positive for longer.

5.
Sci Transl Med ; 14(631): eabj6824, 2022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1685482

ABSTRACT

SARS-CoV-2 variants that escape neutralization and potentially affect vaccine efficacy have emerged. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is incompletely understood. We assessed neutralizing antibody and T cell responses in 44 South African COVID-19 patients either infected with the Beta variant (dominant from November 2020 to May 2021) or infected before its emergence (first wave, Wuhan strain) to provide an overall measure of immune evasion. We show that robust spike-specific CD4 and CD8 T cell responses were detectable in Beta-infected patients, similar to first-wave patients. Using peptides spanning the Beta-mutated regions, we identified CD4 T cell responses targeting the wild-type peptides in 12 of 22 first-wave patients, all of whom failed to recognize corresponding Beta-mutated peptides. However, responses to mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3 of 44) mounted CD8 responses that targeted the mutated regions. Among the spike epitopes tested, we identified three epitopes containing the D215, L18, or D80 residues that were specifically recognized by CD4 T cells, and their mutated versions were associated with a loss of response. This study shows that despite loss of recognition of immunogenic CD4 epitopes, CD4 and CD8 T cell responses to Beta are preserved overall. These observations may explain why several vaccines have retained the ability to protect against severe COVID-19 even with substantial loss of neutralizing antibody activity against Beta.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Epitopes , Humans , Spike Glycoprotein, Coronavirus/genetics
6.
Nature ; 603(7902): 679-686, 2022 03.
Article in English | MEDLINE | ID: covidwho-1638766

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.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Immune Evasion , SARS-CoV-2/isolation & purification , Antibodies, Neutralizing/immunology , Botswana/epidemiology , COVID-19/immunology , COVID-19/transmission , Humans , Models, Molecular , Mutation , Phylogeny , Recombination, Genetic , SARS-CoV-2/classification , SARS-CoV-2/immunology , South Africa/epidemiology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
7.
J Virol Methods ; 302: 114471, 2022 04.
Article in English | MEDLINE | ID: covidwho-1638654

ABSTRACT

Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/virology , Diagnostic Tests, Routine , Humans , RNA , RNA-Dependent RNA Polymerase , SARS-CoV-2/genetics
8.
2021.
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.

9.
Science ; 374(6566): 423-431, 2021 Oct 22.
Article in English | MEDLINE | ID: covidwho-1483977

ABSTRACT

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.


Subject(s)
COVID-19/epidemiology , Epidemiological Monitoring , Genomics , Pandemics , SARS-CoV-2/genetics , Africa/epidemiology , COVID-19/transmission , COVID-19/virology , Genetic Variation , Humans , SARS-CoV-2/isolation & purification
10.
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
13.
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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