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1.
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.

2.
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.

3.
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
4.
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
5.
Lancet ; 399(10323): 437-446, 2022 01 29.
Article in English | MEDLINE | ID: covidwho-1641746

ABSTRACT

BACKGROUND: The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. METHODS: We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. FINDINGS: From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1-0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3-1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2-0·5), after controlling for factors associated with disease severity. INTERPRETATION: Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. FUNDING: The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.


Subject(s)
COVID-19/physiopathology , Hospitalization/statistics & numerical data , SARS-CoV-2/genetics , Severity of Illness Index , Adolescent , Adult , COVID-19/epidemiology , COVID-19/virology , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , Female , Genome, Viral , Humans , Information Storage and Retrieval , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , South Africa/epidemiology , Young Adult
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.
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
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.
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.

10.
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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