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1.
J Med Virol ; 94(8): 3676-3684, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1849500

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.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Genotype , Humans , SARS-CoV-2/genetics , South Africa , Spike Glycoprotein, Coronavirus/genetics
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335264

ABSTRACT

South Africa’s fourth COVID-19 wave was driven predominantly by three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern. We have now identified two new lineages, BA.4 and BA.5. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del, L452R, F486V and the wild type amino acid at Q493. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure with the TaqPath™ COVID-19 qPCR assay. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa from the first week of April 2022 onwards. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.07 - 0.09) and 0.12 (95% CI: 0.09 - 0.15) per day respectively over BA.2 in South Africa.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335252

ABSTRACT

The SARS-CoV-2 Omicron (B.1.1.529) variant first emerged as the BA.1 sub-lineage, with extensive escape from neutralizing immunity elicited by previous infection with other variants, vaccines, or combinations of both 1,2 . Two new sub-lineages, BA.4 and BA.5, are now emerging in South Africa with changes relative to BA.1, including L452R and F486V mutations in the spike receptor binding domain. We isolated live BA.4 and BA.5 viruses and tested them against neutralizing immunity elicited to BA.1 infection in participants who were Omicron/BA.1 infected but unvaccinated (n=24) and participants vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV.2S with breakthrough Omicron/BA.1 infection (n=15). In unvaccinated individuals, FRNT 50 , the inverse of the dilution for 50% neutralization, declined from 275 for BA.1 to 36 for BA.4 and 37 for BA.5, a 7.6 and 7.5-fold drop, respectively. In vaccinated BA.1 breakthroughs, FRNT 50 declined from 507 for BA.1 to 158 for BA.4 (3.2-fold) and 198 for BA.5 (2.6-fold). Absolute BA.4 and BA.5 neutralization levels were about 5-fold higher in this group versus unvaccinated BA.1 infected participants. The observed escape of BA.4 and BA.5 from BA.1 elicited immunity is more moderate than of BA.1 against previous immunity 1,3 . However, the low absolute neutralization levels for BA.4 and BA.5, particularly in the unvaccinated group, are unlikely to protect well against symptomatic infection 4 .This may indicate that, based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave.

4.
Nature ; 2022 May 06.
Article in English | MEDLINE | ID: covidwho-1830078

ABSTRACT

The extent to which Omicron infection1-9, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3-9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19-27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement.

5.
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.

6.
BMC Genomics ; 23(1): 319, 2022 Apr 22.
Article in English | MEDLINE | ID: covidwho-1799119

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Genome, Viral , High-Throughput Nucleotide Sequencing/methods , Humans , SARS-CoV-2/genetics , Whole Genome Sequencing/methods
8.
Nat Commun ; 13(1): 1976, 2022 04 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
9.
Emerg Infect Dis ; 28(5): 1021-1025, 2022 05.
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.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Humans , Pandemics , SARS-CoV-2/genetics , Uganda/epidemiology
10.
Mol Biol Evol ; 39(4)2022 04 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
11.
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
12.
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
13.
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.

14.
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.

15.
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
16.
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
17.
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
18.
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.

19.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296138

ABSTRACT

Mauritius, a small island in the Indian Ocean, has had a unique experience of the SARS-CoV-2 pandemic. In March 2020, Mauritius endured a small first wave and quickly implemented control measures which allowed elimination of local transmission of SARS-CoV-2. When borders to the island reopened, it was accompanied by mandatory quarantine and testing of incoming passengers to avoid reintroduction of the virus into the community. As variants of concern (VOCs) emerged elsewhere in the world, Mauritius began using genomic surveillance to keep track of quarantined cases of these variants. In March 2021, another local outbreak occurred, and sequencing was used to investigate this new wave of local infections. Here, we analyze 154 SARS-CoV-2 viral genomes from Mauritius, which represent 12% of all the infections seem in Mauritius, these were both from specimens of incoming passengers before March 2021 and those of cases during the second wave. Our findings indicate that despite the presence of known VOCs Beta (B.1.351) and Alpha (B.1.1.7) among quarantined passengers, the second wave of local SARS-CoV-2 infections in Mauritius was caused by a single introduction and dominant circulation of the B.1.1.318 virus. The B.1.1.318 variant is characterized by fourteen non-synonymous mutations in the S-gene, with five encoded amino acid substitutions (T95I, E484K, D614G, P681H, D796H) and one deletion (Y144del) in the Spike glycoprotein. This variant seems to be increasing in prevalence and it is now present in 34 countries. This study highlights that despite having stopped the introduction of more transmissible VOCs by travel quarantines, a single undetected introduction of a B.1.1.318 lineage virus was enough to initiate a large local outbreak in Mauritius and demonstrated the need for continuous genomic surveillance to fully inform public health decisions.

20.
2021.
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.

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