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1.
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.
Nat Commun ; 13(1): 1976, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1783980

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Humans , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
5.
Virus Evol ; 8(1): veac024, 2022.
Article in English | MEDLINE | ID: covidwho-1774420

ABSTRACT

The coronavirus disease 2019 (COVID-19) epidemic in Brazil was driven mainly by the spread of Gamma (P.1), a locally emerged variant of concern (VOC) that was first detected in early January 2021. This variant was estimated to be responsible for more than 96 per cent of cases reported between January and June 2021, being associated with increased transmissibility and disease severity, a reduction in neutralization antibodies and effectiveness of treatments or vaccines, and diagnostic detection failure. Here we show that, following several importations predominantly from the USA, the Delta variant rapidly replaced Gamma after July 2021. However, in contrast to what was seen in other countries, the rapid spread of Delta did not lead to a large increase in the number of cases and deaths reported in Brazil. We suggest that this was likely due to the relatively successful early vaccination campaign coupled with natural immunity acquired following prior infection with Gamma. Our data reinforce reports of the increased transmissibility of the Delta variant and, considering the increasing concern due to the recently identified Omicron variant, argues for the necessity to strengthen genomic monitoring on a national level to quickly detect the emergence and spread of other VOCs that might threaten global health.

6.
Emerg Infect Dis ; 28(5)2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1760189

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.

7.
Mol Biol Evol ; 39(4)2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1758789

ABSTRACT

Among the 30 nonsynonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (1) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (2) interactions of Spike with ACE2 receptors, and (3) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron overall previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , COVID-19/genetics , Humans , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
9.
Microb Genom ; 8(3)2022 03.
Article in English | MEDLINE | ID: covidwho-1746154

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is adaptively evolving to ensure its persistence within human hosts. It is therefore necessary to continuously monitor the emergence and prevalence of novel variants that arise. Importantly, some mutations have been associated with both molecular diagnostic failures and reduced or abrogated next-generation sequencing (NGS) read coverage in some genomic regions. Such impacts are particularly problematic when they occur in genomic regions such as those that encode the spike (S) protein, which are crucial for identifying and tracking the prevalence and dissemination dynamics of concerning viral variants. Targeted Sanger sequencing presents a fast and cost-effective means to accurately extend the coverage of whole-genome sequences. We designed a custom set of primers to amplify a 401 bp segment of the receptor-binding domain (RBD) (between positions 22698 and 23098 relative to the Wuhan-Hu-1 reference). We then designed a Sanger sequencing wet-laboratory protocol. We applied the primer set and wet-laboratory protocol to sequence 222 samples that were missing positions with key mutations K417N, E484K, and N501Y due to poor coverage after NGS sequencing. Finally, we developed SeqPatcher, a Python-based computational tool to analyse the trace files yielded by Sanger sequencing to generate consensus sequences, or take preanalysed consensus sequences in fasta format, and merge them with their corresponding whole-genome assemblies. We successfully sequenced 153 samples of 222 (69 %) using Sanger sequencing and confirmed the occurrence of key beta variant mutations (K417N, E484K, N501Y) in the S genes of 142 of 153 (93 %) samples. Additionally, one sample had the Y508F mutation and four samples the S477N. Samples with RT-PCR C t scores ranging from 13.85 to 37.47 (mean=25.70) could be Sanger sequenced efficiently. These results show that our method and pipeline can be used to improve the quality of whole-genome assemblies produced using NGS and can be used with any pairs of the most used NGS and Sanger sequencing platforms.


Subject(s)
Genome, Viral , SARS-CoV-2/genetics , Sequence Analysis, DNA/methods , High-Throughput Nucleotide Sequencing , Mutation
10.
Cell Host Microbe ; 30(2): 154-162.e5, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1708092

ABSTRACT

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, but it evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, it also showed extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion that SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, and this has implications for vaccine breakthrough and reinfections.


Subject(s)
Antibodies, Neutralizing/blood , HIV Infections/pathology , Immune Evasion/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adult , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Cell Line , Chlorocebus aethiops , Female , HIV-1/immunology , Humans , Immunocompromised Host/immunology , Neutralization Tests , SARS-CoV-2/isolation & purification , South Africa , Vaccination , Vero Cells
11.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328633

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 sequence quality produced by 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 sequences classified by Nextclade as good and mediocre compared to the GridION. The MiSeq also had a significantly higher sequence coverage and mutation counts than the GridION. Conclusion: Due to the low sequence coverage, high number of indels, and sensitivity to viral load noted with the GridION when compared to MiSeq, we can conclude that the MiSeq is more favourable for genomic surveillance, as successful genomic surveillance is dependent on high quality, near-whole genome sequences.

12.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327610

ABSTRACT

The SARS-CoV-2 Omicron variant largely escapes neutralizing antibodies elicited by vaccines or infection. However, whether Omicron triggers humoral responses that are cross-reactive to other variants of concern (VOCs) remains largely unknown. We use plasma from 20 unvaccinated and seven vaccinated individuals infected during the Omicron wave in South Africa to test binding, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and neutralization against VOCs. In unvaccinated individuals, Fc effector function and binding antibodies target Omicron and other VOCs at comparable levels. However, Omicron-triggered neutralization is not extensively cross-reactive to VOCs, with 20 to 43-fold reductions in titer. In contrast, vaccination followed by breakthrough Omicron infection improved cross-neutralization of VOCs, with titers exceeding 1:2,900. This has important implications for the vulnerability of unvaccinated Omicron-infected individuals to reinfection by circulating and emerging VOCs. Further, while Omicron-based immunogens may be adequate boosters, they are unlikely to be superior to existing vaccines for priming in SARS-CoV-2 naive individuals.

13.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-326191

ABSTRACT

A 22-year-old female with uncontrolled advanced HIV infection was persistently infected with SARS-CoV-2 beta variant for 9 months, the virus accumulating >20 additional mutations. Antiretroviral therapy suppressed HIV and cleared SARS-CoV-2 within 6-9 weeks. Increased vigilance is warranted to benefit affected individuals and prevent the emergence of novel SARS-CoV-2 variants.

14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321646

ABSTRACT

The rapid identification and isolation of infected individuals remains a key strategy for controlling the spread of SARS-CoV-2. Frequent testing of populations to detect infection early in asymptomatic or presymptomatic individuals can be a powerful tool for intercepting transmission, especially when the viral prevalence is low. However, RT-PCR testing – the gold standard of SARS-CoV-2 diagnosis – is expensive, making regular testing of every individual unfeasible. Sample pooling is one approach to lowering costs. By combining samples and testing them in groups the number of tests required is reduced, substantially lowering costs. Here we report on the implementation of pooling strategies using 3-d and 4-d hypercubes to test a professional sports team in South Africa. We have shown that infected samples can be reliably detected in groups of 27 and 81, with minimal loss of assay sensitivity for samples with individual Ct values up to 32. We report on automation of sample pooling, using a liquid-handling robot and an automated web interface to identify positive samples. We conclude that hypercube pooling allows for the reliable RT-PCR detection of SARS-CoV-2 infection, at significantly lower cost than lateral flow antigen (LFA) tests.

15.
O'Toole, Áine, Hill, Verity, Pybus, Oliver, Watts, Alexander, Bogoch, Issac, Khan, Kamran, Messina, Jane, Tegally, Houriiyah, Lessells, Richard, Giandhari, Jennifer, Pillay, Sureshnee, Tumedi, Kefentse Arnold, Nyepetsi, Gape, Kebabonye, Malebogo, Matsheka, Maitshwarelo, Mine, Madisa, Tokajian, Sima, Hassan, Hamad, Salloum, Tamara, Merhi, Georgi, Koweyes, Jad, Geoghegan, Jemma, de Ligt, Joep, Ren, Xiaoyun, Storey, Matthew, Freed, Nikki, Pattabiraman, Chitra, Prasad, Pramada, Desai, Anita, Vasanthapuram, Ravi, Schulz, Thomas, Steinbrück, Lars, Stadler, Tanja, Parisi, Antonio, Bianco, Angelica, García de Viedma, Darío, Buenestado-Serrano, Sergio, Borges, Vítor, Isidro, Joana, Duarte, Sílvia, Gomes, João Paulo, Zuckerman, Neta, Mandelboim, Michal, Mor, Orna, Seemann, Torsten, Arnott, Alicia, Draper, Jenny, Gall, Mailie, Rawlinson, William, Deveson, Ira, Schlebusch, Sanmarié, McMahon, Jamie, Leong, Lex, Lim, Chuan Kok, Chironna, Maria, Loconsole, Daniela, Bal, Antonin, Josset, Laurence, Holmes, Edward, St. George, Kirsten, Lasek-Nesselquist, Erica, Sikkema, Reina, Oude Munnink, Bas, Koopmans, Marion, Brytting, Mia, Sudha rani, V.; Pavani, S.; Smura, Teemu, Heim, Albert, Kurkela, Satu, Umair, Massab, Salman, Muhammad, Bartolini, Barbara, Rueca, Martina, Drosten, Christian, Wolff, Thorsten, Silander, Olin, Eggink, Dirk, Reusken, Chantal, Vennema, Harry, Park, Aekyung, Carrington, Christine, Sahadeo, Nikita, Carr, Michael, Gonzalez, Gabo, de Oliveira, Tulio, Faria, Nuno, Rambaut, Andrew, Kraemer, Moritz, The, Covid-Genomics U. K. consortium, Network for Genomic Surveillance in South, Africa, Brazil, U. K. Cadde Genomic Network, Swiss Viollier Sequencing, Consortium, Diego, Search Alliance San, National Virus Reference, Laboratory, Seq, Covid Spain, Danish Covid-19 Genome, Consortium, Communicable Diseases Genomic, Network, Dutch National, Sars-CoV-surveillance program, Division of Emerging Infectious, Diseases.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318194

ABSTRACT

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

16.
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
17.
Nature ; 603(7901): 488-492, 2022 03.
Article in English | MEDLINE | ID: covidwho-1661968

ABSTRACT

The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3-6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9-12.


Subject(s)
COVID-19/immunology , COVID-19/virology , Cross Reactions/immunology , Immunity, Cellular , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Adult , Aged , COVID-19 Vaccines/immunology , Convalescence , Hospitalization , Humans , Middle Aged , SARS-CoV-2/chemistry , SARS-CoV-2/classification
18.
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
19.
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
20.
Nature ; 602(7898): 654-656, 2022 02.
Article in English | MEDLINE | ID: covidwho-1616992

ABSTRACT

The emergence of the SARS-CoV-2 variant of concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections1. Here we investigated Omicron escape from neutralization by antibodies from South African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination from individuals who were vaccinated and previously infected with SARS-CoV-2 or vaccinated with no evidence of previous infection. We isolated and sequence-confirmed live Omicron virus from an infected person and observed that Omicron requires the angiotensin-converting enzyme 2 (ACE2) receptor to infect cells. We compared plasma neutralization of Omicron relative to an ancestral SARS-CoV-2 strain and found that neutralization of ancestral virus was much higher in infected and vaccinated individuals compared with the vaccinated-only participants. However, both groups showed a 22-fold reduction in vaccine-elicited neutralization by the Omicron variant. Participants who were vaccinated and had previously been infected exhibited residual neutralization of Omicron similar to the level of neutralization of the ancestral virus observed in the vaccination-only group. These data support the notion that reasonable protection against Omicron may be maintained using vaccination approaches.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Immune Evasion/immunology , Neutralization Tests , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Line , Chlorocebus aethiops , Humans , Mutation , SARS-CoV-2/classification , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
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