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Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil.
Microbiol Spectr. 2022 02 23; 10(1):e0236621.MS

Abstract

The Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly Δ144 or Δ141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we did not find an increased incidence of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sublineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting more infectious variants or antibody evasion mutations is expected to increase. IMPORTANCE The continuous evolution of SARS-CoV-2 is an expected phenomenon that will continue to happen due to the high number of cases worldwide. The present study analyzed how a Variant of Concern (VOC) could still circulate in a population hardly affected by two COVID-19 waves and with vaccination in progress. Our results showed that the answer behind that was a new generation of Gamma-like viruses, which emerged locally carrying mutations that made it more transmissible and more capable of spreading, partially evading prior immunity triggered by natural infections or vaccines. With thousands of new cases daily, the current pandemics scenario suggests that SARS-CoV-2 will continue to evolve and efforts to reduce the number of infected subjects, including global equitable access to COVID-19 vaccines, are mandatory. Thus, until the end of pandemics, the SARS-CoV-2 genomic surveillance will be an essential tool to better understand the drivers of the viral evolutionary process.

Authors+Show Affiliations

Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil. Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil. Fundação Centro de Controle de Oncologia do Estado do Amazonas, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Diversidade Microbiana da Amazônia com Importância para a Saúde, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil. Fundação de Vigilância em Saúde do Amazonas - Dra. Rosemary Costa Pinto, Manaus, Amazonas, Brazil.Fundação de Vigilância em Saúde do Amazonas - Dra. Rosemary Costa Pinto, Manaus, Amazonas, Brazil.Laboratório Central de Saúde Pública do Amazonas, Manaus, Amazonas, Brazil.Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.Hospital Adventista de Manaus, Manaus, Amazonas, Brazil.Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil.Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil. Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil.Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil. Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.Fundação de Vigilância em Saúde do Amazonas - Dra. Rosemary Costa Pinto, Manaus, Amazonas, Brazil. Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil.Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil. Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil.Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil. Laboratório de Diagnóstico e Controle e Doenças Infecciosas da Amazônia, Instituto Leônidas e Maria Deane, Fiocruz, Manaus, Amazonas, Brazil.Secretaria de Saúde de Aparecida de Goiânia, Goiás, Brazil.Secretaria de Saúde de Aparecida de Goiânia, Goiás, Brazil.Laboratório de Virologia e Cultivo Celular, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.HLAGYN-Laboratório de Imunologia de Transplantes de Goiás, Aparecida de Goiânia, Goiás, Brazil.HLAGYN-Laboratório de Imunologia de Transplantes de Goiás, Aparecida de Goiânia, Goiás, Brazil.Laboratório Analitico de Competências Moleculares e Epidemiológicas, Fundação Oswaldo Cruz Ceará, Fiocruz, Eusébio, Ceará, Brazil.Laboratório Analitico de Competências Moleculares e Epidemiológicas, Fundação Oswaldo Cruz Ceará, Fiocruz, Eusébio, Ceará, Brazil.Unidade de Apoio Diagnóstico à COVID-19, Fundação Oswaldo Cruz Ceará, Fiocruz, Eusébio, Ceará, Brazil.Departamento de Virologia, Instituto Aggeu Magalhães, Fiocruz, Recife, Pernambuco, Brazil.Departamento de Virologia, Instituto Aggeu Magalhães, Fiocruz, Recife, Pernambuco, Brazil.Departamento de Virologia, Instituto Aggeu Magalhães, Fiocruz, Recife, Pernambuco, Brazil.Departamento de Entomologia e Núcleo de Bioinformática, Instituto Aggeu Magalhães, Fiocruz, Recife, Pernambuco, Brazil.Departamento de Biologia, Centro de Ciências Exatas, Naturais e da Saúde, Universidade Federal do Espírito Santo, Alegre, Espírito Santo, Brazil.Instituto Gonçalo Moniz, Fiocruz, Salvador, Bahia, Brazil.Laboratório de Vírus Respiratórios e do Sarampo (LVRS), Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.Laboratório de Vírus Respiratórios e do Sarampo (LVRS), Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35196783

Citation

Naveca, Felipe Gomes, et al. "Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil." Microbiology Spectrum, vol. 10, no. 1, 2022, pp. e0236621.
Naveca FG, Nascimento V, Souza V, et al. Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil. Microbiol Spectr. 2022;10(1):e0236621.
Naveca, F. G., Nascimento, V., Souza, V., Corado, A. L., Nascimento, F., Silva, G., Mejía, M. C., Brandão, M. J., Costa, Á., Duarte, D., Pessoa, K., Jesus, M., Gonçalves, L., Fernandes, C., Mattos, T., Abdalla, L., Santos, J. H., Martins, A., Chui, F. M., ... Bello, G. (2022). Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil. Microbiology Spectrum, 10(1), e0236621. https://doi.org/10.1128/spectrum.02366-21
Naveca FG, et al. Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil. Microbiol Spectr. 2022 02 23;10(1):e0236621. PubMed PMID: 35196783.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil. AU - Naveca,Felipe Gomes, AU - Nascimento,Valdinete, AU - Souza,Victor, AU - Corado,André de Lima, AU - Nascimento,Fernanda, AU - Silva,George, AU - Mejía,Matilde Contreras, AU - Brandão,Maria Júlia, AU - Costa,Ágatha, AU - Duarte,Débora, AU - Pessoa,Karina, AU - Jesus,Michele, AU - Gonçalves,Luciana, AU - Fernandes,Cristiano, AU - Mattos,Tirza, AU - Abdalla,Ligia, AU - Santos,João Hugo, AU - Martins,Alex, AU - Chui,Fabiola Mendonça, AU - Val,Fernando Fonseca, AU - de Melo,Gisely Cardoso, AU - Xavier,Mariana Simão, AU - Sampaio,Vanderson de Souza, AU - Mourão,Maria Paula, AU - Lacerda,Marcus Vinícius, AU - Batista,Érika Lopes Rocha, AU - Magalhães,Alessandro Leonardo Álvares, AU - Dábilla,Nathânia, AU - Pereira,Lucas Carlos Gomes, AU - Vinhal,Fernando, AU - Miyajima,Fabio, AU - Dias,Fernando Braga Stehling, AU - Dos Santos,Eduardo Ruback, AU - Coêlho,Danilo, AU - Ferraz,Matheus, AU - Lins,Roberto, AU - Wallau,Gabriel Luz, AU - Delatorre,Edson, AU - Gräf,Tiago, AU - Siqueira,Marilda Mendonça, AU - Resende,Paola Cristina, AU - Bello,Gonzalo, AU - ,, Y1 - 2022/02/23/ PY - 2022/2/24/entrez PY - 2022/2/25/pubmed PY - 2022/3/5/medline KW - Brazil KW - COVID-19 KW - SARS-CoV-2 KW - coronavirus KW - variant gamma KW - virus evolution SP - e0236621 EP - e0236621 JF - Microbiology spectrum JO - Microbiol Spectr VL - 10 IS - 1 N2 - The Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly Δ144 or Δ141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we did not find an increased incidence of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sublineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting more infectious variants or antibody evasion mutations is expected to increase. IMPORTANCE The continuous evolution of SARS-CoV-2 is an expected phenomenon that will continue to happen due to the high number of cases worldwide. The present study analyzed how a Variant of Concern (VOC) could still circulate in a population hardly affected by two COVID-19 waves and with vaccination in progress. Our results showed that the answer behind that was a new generation of Gamma-like viruses, which emerged locally carrying mutations that made it more transmissible and more capable of spreading, partially evading prior immunity triggered by natural infections or vaccines. With thousands of new cases daily, the current pandemics scenario suggests that SARS-CoV-2 will continue to evolve and efforts to reduce the number of infected subjects, including global equitable access to COVID-19 vaccines, are mandatory. Thus, until the end of pandemics, the SARS-CoV-2 genomic surveillance will be an essential tool to better understand the drivers of the viral evolutionary process. SN - 2165-0497 UR - https://www.unboundmedicine.com/medline/citation/35196783/Spread_of_Gamma__P_1__Sub_Lineages_Carrying_Spike_Mutations_Close_to_the_Furin_Cleavage_Site_and_Deletions_in_the_N_Terminal_Domain_Drives_Ongoing_Transmission_of_SARS_CoV_2_in_Amazonas_Brazil_ DB - PRIME DP - Unbound Medicine ER -