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Giovanetti, M.; Slavov, S. N.; Fonseca, V.; Wilkinson, E.; Tegally, H.; Patané, J. S. L.; Viala, V. L.; San, J. E.; Rodrigues, E. S.; Vieira Santos, E.; Aburjaile, F.; Xavier, J.; Fritsch, H.; Ribeiro Adelino, T. E.; Pereira, F.; Leal, A.; Campos de Melo Iani, F.; de Carvalho Pereira, G.; Vazquez, C.; Mercedes Estigarribia Sanabria, G.; de Oliveira, E. C.; Demarchi, L.; Croda, J.; Dos Santos Bezerra, R.; Oliveira de Lima, L. P.; Martins, A. J.; Dos Santos Barros, C. R.; Marqueze, E. C.; de Souza Todao Bernardino, J.; Moretti, D. B.; Brassaloti, R. A.; de Lello Rocha Campos Cassano, R.; Drummond Sampaio Corrêa Mariani, P.; Kitajima, J. P.; Santos, B.; Proto-Siqueira, R.; Cantarelli, V. V.; Tosta, S.; Brandão Nardy, V.; Reboredo de Oliveira da Silva, L.; Astete Gómez, M. K.; Lima, J. G.; Ribeiro, A. A.; Guimarães, N. R.; Watanabe, L. T.; Barbosa Da Silva, L.; da Silva Ferreira, R.; MP, F. da Penha, Ortega, M. J.; Gómez de la Fuente, A.; Villalba, S.; Torales, J.; Gamarra, M. L.; Aquino, C.; Martínez Figueredo, G. P.; Fava, W. S.; Motta-Castro, A. R. C.; Venturini, J.; do Vale Leone de Oliveira, S. M.; Cavalheiro Maymone Gonçalves, C.; Debur Rossa, M. D. C.; Becker, G. N.; Presibella, M. M.; Marques, N. Q.; Riediger, I. N.; Raboni, S.; Coelho, G. M.; Cataneo, A. H. D.; Zanluca, C.; Dos Santos, C. N. D.; Assato, P. A.; Allan da Silva da Costa, F.; Poleti, M. D.; Chagas Lesbon, J. C.; Mattos, E. C.; Banho, C. A.; Sacchetto, L.; Moraes, M. M.; Tommasini Grotto, R. M.; Souza-Neto, J. A.; Nogueira, M. L.; Fukumasu, H.; Coutinho, L. L.; Calado, R. T.; Neto, R. M.; Bispo de Filippis, A. M.; Venancio da Cunha, R.; Freitas, C.; Leonel Peterka, C. R.; Rangel Fernandes, C. F.; de Araújo, W. N.; do Carmo Said, R. F.; Almiron, M.; Campelo de Albuquerque, E. Melo C. F.; Lourenço, J.; de Oliveira, T.; Holmes, E. C.; Haddad, R.; Sampaio, S. C.; Elias, M. C.; Kashima, S.; de Alcantara, L. C. J.; Covas, D. T..
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-332259


Brazil has experienced some of the highest numbers of COVID-19 cases and deaths globally and from May 2021 made Latin America a pandemic epicenter. Although SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, important gaps remain in our understanding of virus transmission dynamics at the national scale. Here, we describe the genomic epidemiology of SARS-CoV-2 using near-full genomes sampled from 27 Brazilian states and a bordering country - Paraguay. We show that the early stage of the pandemic in Brazil was characterised by the co-circulation of multiple viral lineages, linked to multiple importations predominantly from Europe, and subsequently characterized by large local transmission clusters. As the epidemic progressed under an absence of effective restriction measures, there was a local emergence and onward international spread of Variants of Concern (VOC) and Variants Under Monitoring (VUM), including Gamma (P.1) and Zeta (P.2). In addition, we provide a preliminary genomic overview of the epidemic in Paraguay, showing evidence of importation from Brazil. These data reinforce the usefulness and need for the implementation of widespread genomic surveillance in South America as a toolkit for pandemic monitoring that provides a means to follow the real-time spread of emerging SARS-CoV-2 variants with possible implications for public health and immunization strategies.

Preprint in English | EMBASE | ID: ppcovidwho-327015


Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated whether neutralizing immunity elicited by Omicron also enhances neutralizing immunity of the Delta variant. We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals. Along with emerging data indicating that Omicron, at this time in the pandemic, is less pathogenic than Delta, such an outcome may have positive implications in terms of decreasing the Covid-19 burden of severe disease.

Preprint in English | EMBASE | ID: ppcovidwho-326897


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta 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) 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, 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.

Preprint in English | MEDLINE | ID: ppcovidwho-325667


Omicron variant (B.1.1.529) infections are rapidly expanding worldwide, often in settings where the Delta variant (B.1.617.2) was dominant. We investigated whether neutralizing immunity elicited by Omicron infection would also neutralize the Delta variant and the role of prior vaccination. We enrolled 23 South African participants infected with Omicron a median of 5 days post-symptoms onset (study baseline) with a last follow-up sample taken a median of 23 days post-symptoms onset. Ten participants were breakthrough cases vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV2.S. In vaccinated participants, neutralization of Omicron increased from a geometric mean titer (GMT) FRNT50 of 28 to 378 (13.7-fold). Unvaccinated participants had similar Omicron neutralization at baseline but increased from 26 to only 113 (4.4-fold) at follow-up. Delta virus neutralization increased from 129 to 790, (6.1-fold) in vaccinated but only 18 to 46 (2.5-fold, not statistically significant) in unvaccinated participants. Therefore, in Omicron infected vaccinated individuals, Delta neutralization was 2.1-fold higher at follow-up relative to Omicron. In a separate group previously infected with Delta, neutralization of Delta was 22.5-fold higher than Omicron. Based on relative neutralization levels, Omicron re-infection would be expected to be more likely than Delta in Delta infected individuals, and in Omicron infected individuals who are vaccinated. This may give Omicron an advantage over Delta which may lead to decreasing Delta infections in regions with high infection frequencies and high vaccine coverage.

PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296585


Characterizing SARS-CoV-2 evolution in specific geographies may help predict the properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from the ancestral virus in a person with advanced HIV disease. Infection was before the emergence of the Beta variant first identified in South Africa, and the Delta variant. We compared early and late evolved virus to the ancestral, Beta, Alpha, and Delta viruses and tested against convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, whereas late virus was similar to Beta, exhibiting vaccine escape and, despite pre-dating Delta, strong escape of Delta-elicited neutralization. This example is consistent with the notion that variants arising in immune-compromised hosts, including those with advanced HIV disease, may evolve immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections. Highlights: A prolonged ancestral SARS-CoV-2 infection pre-dating the emergence of Beta and Delta resulted in evolution of a Beta-like serological phenotypeSerological phenotype includes strong escape from Delta infection elicited immunity, intermediate escape from ancestral virus immunity, and weak escape from Beta immunityEvolved virus showed substantial but incomplete escape from antibodies elicited by BNT162b2 vaccination. Graphical abstract:

PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296584


The emergence of the SARS-CoV-2 Omicron variant, first identified in South Africa, may compromise the ability of vaccine and previous infection (1) elicited immunity to protect against new infection. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine in people who were vaccinated only or vaccinated and previously infected. We also investigated whether the virus still requires binding to the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa. We then compared neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation. Neutralization was by blood plasma from South African BNT162b2 vaccinated individuals. We observed that Omicron still required the ACE2 receptor to infect but had extensive escape of Pfizer elicited neutralization. However, 5 out of 6 of the previously infected, Pfizer vaccinated individuals, all of them with high neutralization of D614G virus, showed residual neutralization at levels expected to confer protection from infection and severe disease (2). While vaccine effectiveness against Omicron is still to be determined, these data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly by boosting, could maintain reasonable effectiveness against Omicron. If neutralization capacity is lower or wanes with time, protection against infection is likely to be low. However, protection against severe disease, requiring lower neutralization levels and involving T cell immunity, would likely be maintained.