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  • article 22 Citação(ões) na Scopus
    Field and classroom initiatives for portable sequence-based monitoring of dengue virus in Brazil
    (2021) ADELINO, Talita Emile Ribeiro; GIOVANETTI, Marta; FONSECA, Vagner; XAVIER, Joilson; ABREU, Alvaro Salgado de; NASCIMENTO, Valdinete Alves do; DEMARCHI, Luiz Henrique Ferraz; OLIVEIRA, Marluce Aparecida Assuncao; SILVA, Vinicius Lemes da; MELLO, Arabela Leal e Silva de; CUNHA, Gabriel Muricy; ABRANTES, Jayra Juliana Paiva Alves; WATANABE, Luiz Takao; REGO, Marta Ferreira da Silva; NARDY, Vanessa Brandao; AGUIAR, Shirlei Ferreira de; SANTOS, Fabiana Cristina Pereira dos; QUEIROZ, Alice Louize Nunes; NUNES, Bruno Tardelli Diniz; MARTINS, Livia Caricio; NUNES, Marcio Roberto Teixeira; SANTOS, Roselene Hans; SALLES, Flavia Cristina da Silva; CLARO, Ingra Morales; JESUS, Jaqueline Goes de; CANDIDO, Darlan da Silva; FABBRI, Cintia Marcela; GONZALEZ, Claudia; SAEZ, Lisseth; CHEN-GERMAN, Maria; BARRERA, Jaime Lagos; RAMIREZ-GONZALEZ, Jose Ernesto; OLIVEIRA, Elaine Cristina de; CAMPOS, Josefina; FALLER, Noelia Morel; VILLALOBOS, Marta Eugenia Viquez; KASLIN, Roberto; CISNEROS, Silvia Paola Salgado; ABURJAILE, Flavia Figueira; AMARAL, Carolina Dourado; FREIRE, Danielle Bandeira Costa de Sousa; CRUZ, Laura Nogueira; MATTOS, Daniel; CHAMON JUNIOR, Jorge Antonio; LANDEIRA, Leandro Ferreira Lopes; MENEZES, Mariane Talon de; ORIOLI, Ieda Maria; FERRAZ, Ariane Coelho; OLIVEIRA, Daiane Teixeira de; REIS, Alexandre Barbosa; COTA, Renata Guerra de Sa; BEZERRA, Rafael dos Santos; FALCAO, Melissa Barreto; CARVALHO, Rodrigo Dias de Oliveira; IANI, Felipe Campos de Melo; FILIPPIS, Ana Maria Bispo de; ABREU, Andre Luiz de; JESUS, Ronaldo de; ALBUQUERQUE, Carlos Frederico Campelo de; RICO, Jairo Mendez; SAID, Rodrigo Fabiano do Carmo; SILVA, Joscelio Aguiar; MOURA, Noely Fabiana Oliveira de; LEITE, Priscila; FRUTUOSO, Livia Carla Vinhal; HADDAD, Simone Kashima; MARTINEZ, Alexander; BARRETO, Fernanda Khouri; VAZQUEZ, Cynthia Carolina; CUNHA, Rivaldo Venancio da; ARAUJO, Emerson Luiz Lima; TOSTA, Stephane Fraga de Oliveira; FABRI, Allison de Araujo; CHALHOUB, Flavia Lowen Levy; LEMOS, Poliana da Silva; BRUYCKER-NOGUEIRA, Fernanda De; LICHS, Gislene Garcia de Castro; ZARDIN, Marina Castilhos Souza Umaki; SEGOVIA, Fatima Maria Cardozo; GONCALVES, Crhistinne Cavalheiro Maymone; GRILLO, Zoraida Del Carmen Fernandez; SLAVOV, Svetoslav Nanev; PEREIRA, Luiz Augusto; MENDONCA, Ana Flavia; PEREIRA, Felicidade Mota; MAGALHAES, Jurandy Junior Ferraz de; SANTOS JUNIOR, Agenor de Castro Moreira dos; LIMA, Maricelia Maia de; NOGUEIRA, Rita Maria Ribeiro; GOES-NETO, Aristoteles; AZEVEDO, Vasco Ariston de Carvalho; RAMALHO, Dario Brock; OLIVEIRA, Wanderson Kleber; MACARIO, Eduardo Marques; MEDEIROS, Arnaldo Correia de; PIMENTEL, Victor; HOLMES, Edward C.; OLIVEIRA, Tulio de; LOURENCO, Jose; ALCANTARA, Luiz Carlos Junior; CERQUEIRA, Erenilde Marques de; GRAF, Tiago; RAMALHO, Walter; NAVEGANTES, Wildo; REIS, Renato Barbosa; DUARTE, Clara Guerra; PEREIRA, Maira Alves; SILVA, Paulo Eduardo de Souza da; SOUZA, Raoni Almeida de; PAUVOLID-CORREA, Alex; PAIVA, Anne Aline Pereira de; FRITSCH, Hegger Machado; MARES-GUIA, Maria Angelica; TORRES, Maria Celeste; LIMA, Mauricio Teixeira; SEQUEIRA, Patricia; MARQUES, William de Almeida; JESUS, Jorlan Fernandes de; NAVECA, Felipe Gomes; SILVA, Alessandra Lima; PINTO, Anne Cybelle; JAISWAL, Arun Kumar; LOPES, Elisson Nogueira; COSTA, Francielly Morais Rodrigues da; QUINTANILHA-PEIXOTO, Gabriel; SOARES, Gilson Carlos; FONSECA, Paula Luize Camargos; SOUZA, Renan Pedra de; KATO, Rodrigo Bentes; SANTOS, Rodrigo Profeta Silveira; TIWARI, Sandeep; NOGUEIRA, Wylerson Guimaraes; SANTOS, Beatriz Senra Alvares da Silva; BUENO, Bruna Lopes; SIQUEIRA, Isadora Cristina de; VALLVE, Lourdes Farre; BORBA, Melina Mosquera Navarro; MAZZETTO, Alix Sandra; AGUIAR, Francisco de Assis Araujo; GOMES, Irenio da Silva
    Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015-2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses. Here, the authors present results of the ZiBRA-2 project (https://www.zibra2project.org) which is an arbovirus surveillance project, across the Midwest of Brazil using a mobile genomics laboratory, combined with a genomic surveillance training program that targeted post-graduate students, laboratory technicians, and health practitioners in universities and laboratories.
  • article 61 Citação(ões) na Scopus
    Importation and early local transmission of COVID-19 in Brazil, 2020
    (2020) JESUS, Jaqueline Goes de; SACCHI, Claudio; CANDIDO, Darlan da Silva; CLARO, Ingra Morales; SALE, Flavia Cristina Silva; MANULI, Erika Regina; SILVA, Daniela Bernardes Borges da; PAIVA, Terezinha Maria de; PINHO, Margarete Aparecida Benega; SANTOS, Katia Correa de Oliveira; HILL, Sarah Catherine; AGUIAR, Renato Santana; ROMERO, Filipe; SANTOS, Fabiana Cristina Pereira dos; GONCALVES, Claudia Regina; TIMENETSKY, Maria do Carmo; QUICK, Joshua; CRODA, Julio Henrique Rosa; OLIVEIRA, Wanderson de; RAMBAUT, Andrew; PYBUS, Oliver G.; LOMAN, Nicholas J.; SABINO, Ester Cerdeira; FARIA, Nuno Rodrigues
    We conducted the genome sequencing and analysis of the first confirmed COVID-19 infections in Brazil. Rapid sequencing coupled with phylogenetic analyses in the context of travel history corroborate multiple independent importations from Italy and local spread during the initial stage of COVID-19 transmission in Brazil.
  • article 43 Citação(ões) na Scopus
    Local Transmission of SARS-CoV-2 Lineage B.1.1.7, Brazil, December 2020
    (2021) CLARO, Ingra Morales; SALES, Flavia Cristina da Silva; RAMUNDO, Mariana Severo; CANDIDO, Darlan S.; SILVA, Camila A. M.; JESUS, Jaqueline Goes de; MANULI, Erika R.; OLIVEIRA, Cristina Mendes de; SCARPELLI, Luciano; CAMPANA, Gustavo; PYBUS, Oliver G.; SABINO, Ester Cerdeira; FARIA, Nuno Rodrigues; LEVI, Jose Eduardo
    In December 2020, research surveillance detected the B.1.1.7 lineage of severe acute respiratory syndrome coronavirus 2 in Sao Paulo, Brazil. Rapid genomic sequencing and phylogenetic analysis revealed 2 distinct introductions of the lineage. One patient reported no international travel. There may be more infections with this lineage in Brazil than reported.
  • article 879 Citação(ões) na Scopus
    Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil
    (2021) FARIA, Nuno R.; MELLAN, Thomas A.; WHITTAKER, Charles; CLARO, Ingra M.; CANDIDO, Darlan da S.; MISHRA, Swapnil; CRISPIM, Myuki A. E.; SALES, Flavia C.; HAWRYLUK, Iwona; MCCRONE, John T.; HULSWIT, Ruben J. G.; FRANCO, Lucas A. M.; RAMUNDO, Mariana S.; JESUS, Jaqueline G. de; ANDRADE, Pamela S.; COLETTI, Thais M.; FERREIRA, Giulia M.; SILVA, Camila A. M.; MANULI, Erika R.; PEREIRA, Rafael H. M.; PEIXOTO, Pedro S.; KRAEMER, Moritz U.; GABURO JR., Nelson; CAMILO, Cecilia da C.; HOELTGEBAUM, Henrique; SOUZA, William M.; ROCHA, Esmenia C.; SOUZA, Leandro M. de; PINHO, Mariana C. de; ARAUJO, Leonardo J. T.; V, Frederico S. Malta; LIMA, Aline B. de; SILVA, Joice do P.; ZAULI, Danielle A. G.; FERREIRA, Alessandro C. de S.; SCHNEKENBERG, Ricardo P.; LAYDON, Daniel J.; WALKER, Patrick G. T.; SCHLUETER, Hannah M.; SANTOS, Ana L. P. dos; VIDAL, Maria S.; CARO, Valentina S. Del; FILHO, Rosinaldo M. F.; SANTOS, Helem M. dos; AGUIAR, Renato S.; PROENCA-MODENA, Jose L. P.; NELSON, Bruce; HAY, James A.; MONOD, Melodie; MISCOURIDOU, Xenia; COUPLAND, Helen; SONABEND, Raphael; VOLLMER, Michaela; GANDY, Axel; PRETE JR., Carlos A.; NASCIMENTO, Vitor H.; SUCHARD, Marc A.; BOWDEN, Thomas A.; POND, Sergei L. K.; WU, Chieh-Hsi; RATMANN, Oliver; FERGUSON, Neil M.; DYE, Christopher; LOMAN, Nick J.; LEMEY, Philippe; RAMBAUT, Andrew; FRAIJI, Nelson A.; CARVALHO, Maria do P. S. S.; PYBUS, Oliver G.; FLAXMAN, Seth; BHATT, Samir; SABINO, Ester C.
    Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.
  • article 2 Citação(ões) na Scopus
    SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains
    (2023) MENDES-CORREA, Maria Cassia; SALOMAO, Matias Chiarastelli; GHILARDI, Fabio; TOZETTO-MENDOZA, Tania Regina; VILLAS-BOAS, Lucy Santos; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; COSTA, Antonio Charlys da; LEAL, Fabio E.; FERRAZ, Andrea de Barros Coscelli; SALES, Flavia C. S.; CLARO, Ingra M.; FERREIRA, Noely E.; PEREIRA, Geovana M.; JR, Almir Ribeiro da Silva; FREIRE, Wilton; ESPINOZA, Evelyn Patricia Sanchez; MANULI, Erika R.; ROMANO, Camila M.; JESUS, Jaqueline G. de; SABINO, Ester C.; WITKIN, Steven S.
    Introduction-The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods-We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested via RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results-A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS-CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.
  • article 5 Citação(ões) na Scopus
    Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing
    (2023) CLARO, I. M.; RAMUNDO, M. S.; COLETTI, T. M.; SILVA, C. A. M. da; VALENCA, I. N.; CANDIDO, D. S.; SALES, F. C. S.; MANULI, E. R.; JESUS, J. G. de; PAULA, A. de; FELIX, A. C.; ANDRADE, P. D. S.; PINHO, M. C.; SOUZA, W. M.; AMORIM, M. R.; PROENCA-MODENA, J. L.; KALLAS, E. G.; LEVI, J. E.; FARIA, N. R.; SABINO, E. C.; LOMAN, N. J.; QUICK, J.
    Emerging and re-emerging viruses are a global health concern. Genome sequencing as an approach for monitoring circulating viruses is currently hampered by complex and expensive methods. Untargeted, metagenomic nanopore sequencing can provide genomic information to identify pathogens, prepare for or even prevent outbreaks. SMART (Switching Mechanism at the 5′ end of RNA Template) is a popular approach for RNA-Seq but most current methods rely on oligo-dT priming to target polyadenylated mRNA molecules. We have developed two random primed SMART-Seq approaches, a sequencing agnostic approach ‘SMART-9N’ and a version compatible rapid adapters  available from Oxford Nanopore Technologies ‘Rapid SMART-9N’. The methods were developed using viral isolates, clinical samples, and compared to a gold-standard amplicon-based method. From a Zika virus isolate the SMART-9N approach recovered 10kb of the 10.8kb RNA genome in a single nanopore read. We also obtained full genome coverage at a high depth coverage using the Rapid SMART-9N, which takes only 10 minutes and costs up to 45% less than other methods. We found the limits of detection of these methods to be 6 focus forming units (FFU)/mL with 99.02% and 87.58% genome coverage for SMART-9N and Rapid SMART-9N respectively. Yellow fever virus plasma samples and SARS-CoV-2 nasopharyngeal samples previously confirmed by RT-qPCR with a broad range of Ct-values were selected for validation. Both methods produced greater genome coverage when compared to the multiplex PCR approach and we obtained the longest single read of this study (18.5 kb) with a SARS-CoV-2 clinical sample, 60% of the virus genome using the Rapid SMART-9N method. This work demonstrates that SMART-9N and Rapid SMART-9N are sensitive, low input, and long-read compatible alternatives for RNA virus detection and genome sequencing and Rapid SMART-9N improves the cost, time, and complexity of laboratory work.
  • article 22 Citação(ões) na Scopus
    Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019
    (2020) JESUS, Jaqueline Goes de; DUTRA, Karina Rocha; SALES, Flavia Cristina da Silva; CLARO, Ingra Morales; TERZIAN, Ana Carolina; CANDIDO, Darlan da Silva; HILL, Sarah C.; THEZE, Julien; TORRES, Celeste; D'AGOSTINI, Tatiana Lang; FELIX, Alvina Clara; REIS, Andreia F. Negri; ALCANTAR, Luiz Carlos Junior; ABREU, Andre L. de; CRODA, Julio H. R.; OLIVEIRA, Wanderson K. de; FILIPIS, Ana Maria Bispo de; CAMIS, Maria do Carmo Rodrigues dos Santos; ROMANO, Camila Malta; LOMAN, Nick J.; PYBUS, Oliver G.; SABINO, Ester Cerdeira; NOGUEIRA, Mauricio L.; FARIA, Nuno Rodrigues
    BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. Sao Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of Sao Paulo State, Araraquara and Sao Jose do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.
  • article 29 Citação(ões) na Scopus
    Genomic Surveillance of Yellow Fever Virus Epizootic in Sao Paulo, Brazil, 2016-2018
    (2020) HILL, Sarah C.; SOUZA, Renato de; THEZE, Julien; CLARO, Ingra; AGUIAR, Renato S.; ABADE, Leandro; SANTOS, Fabiana C. P.; CUNHA, Mariana S.; NOGUEIRA, Juliana S.; SALLES, Flavia C. S.; ROCCO, Iray M.; MAEDA, Adriana Y.; VASAMI, Fernanda G. S.; PLESSIS, Louis du; SILVEIRA, Paola P.; JESUS, Jaqueline G. de; QUICK, Joshua; FERNANDES, Natalia C. C. A.; GUERRA, Juliana M.; RESSIO, Rodrigo A.; GIOVANETTI, Marta; ALCANTARA, Luiz C. J.; CIRQUEIRA, Cinthya S.; DIAZ-DELGADO, Josue; MACEDO, Fernando L. L.; TIMENETSKY, Maria do Carmo S. T.; PAULA, Regiane de; SPINOLA, Roberta; DEUS, Juliana Telles de; MUCCI, Luis F.; TUBAKI, Rosa Maria; MENEZES, Regiane M. T. de; RAMOS, Patricia L.; ABREU, Andre L. de; CRUZ, Laura N.; LOMAN, Nick; DELLICOUR, Simon; PYBUS, Oliver G.; SABINO, Ester C.; FARIA, Nuno R.
    Sao Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in Sao Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spill over to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in Sao Paulo, we generated and analysed virus genomic data and epizootic case data from NHP in Sao Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in Sao Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in Sao Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in Sao Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern Sao Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of Sao Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in Sao Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species.
  • article 75 Citação(ões) na Scopus
    Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study
    (2021) SOUZA, William M.; AMORIM, Mariene R.; SESTI-COSTA, Renata; COIMBRA, Lais D.; BRUNETTI, Natalia S.; TOLEDO-TEIXEIRA, Daniel A.; SOUZA, Gabriela F. de; MURARO, Stefanie P.; PARISE, Pierina L.; BARBOSA, Priscilla P.; BISPO-DOS-SANTOS, Karina; MOFATTO, Luciana S.; SIMEONI, Camila L.; CLARO, Ingra M.; DUARTE, Adriana S. S.; COLETTI, Thais M.; ZANGIROLAMI, Audrey B.; COSTA-LIMA, Carolina; GOMES, Arilson B. S. P.; I, Lucas Buscaratti; SALES, Flavia C.; COSTA, Vitor A.; FRANCO, Lucas A. M.; CANDIDO, Darlan S.; PYBUS, Oliver G.; JESUS, Jaqueline G. de; SILVA, Camila A. M.; RAMUNDO, Mariana S.; FERREIRA, Giulia M.; PINHO, Mariana C.; SOUZA, Leandro M.; ROCHA, Esmenia C.; ANDRADE, Pamela S.; CRISPIM, Myuki A. E.; MAKTURA, Grazielle C.; MANULI, Erika R.; SANTOS, Magnun N. N.; CAMILO, Cecilia C.; ANGERAMI, Rodrigo N.; MORETTI, Maria L.; SPILKI, Fernando R.; ARNS, Clarice W.; ADDAS-CARVALHO, Marcelo; BENITES, Bruno D.; VINOLO, Marco A. R.; MORI, Marcelo A. S.; GABURO, Nelson; DYE, Christopher; MARQUES-SOUZA, Henrique; MARQUES, Rafael E.; FARIAS, Alessandro S.; DIAMOND, Michael S.; FARIA, Nuno R.; SABINO, Ester C.; GRANJA, Fabiana; PROENCA-MODENA, Jose Luiz
    Background Mutations accrued by SARS-CoV-2 lineage P.1-first detected in Brazil in early January, 2021-include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response. Methods We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17-38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134-230 days after the second dose). Antibody neutralisation of P.1/28, P.1/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT50, defined as the reciprocal value of the sample dilution that showed 50% protection against cytopathic effects). Findings In terms of VNT50, plasma from individuals previously infected with SARS-CoV-2 had an 8.6 times lower neutralising capacity against the P.1 isolates (median VNT50 30 [IQR <20-45] for P.1/28 and 30 [<20-40] for P.1/30) than against the lineage B isolate (260 [160-400]), with a binominal model showing significant reductions in lineage P.1 isolates compared with the lineage B isolate (p <= 0.0001). Efficient neutralisation of P.1 isolates was not seen with plasma samples collected from individuals vaccinated with a first dose of CoronaVac 20-23 days earlier (VNT(50)s below the limit of detection [<20] for most plasma samples), a second dose 17-38 days earlier (median VNT50 24 [IQR <20-25] for P.1/28 and 28 [<20-25] for P.1/30), or a second dose 134-260 days earlier (all VNT(50)s below limit of detection). Median VNT(50)s against the lineage B isolate were 20 (IQR 20-30) after a first dose of CoronaVac 20-23 days earlier, 75 (<20-263) after a second dose 17-38 days earlier, and 20 (<20-30) after a second dose 134-260 days earlier. In plasma collected 17-38 days after a second dose of CoronaVac, neutralising capacity against both P.1 isolates was significantly decreased (p=0.0051 for P.1/28 and p=0.0336 for P.1/30) compared with that against the lineage B isolate. All data were corroborated by results obtained through plaque reduction neutralisation tests. Interpretation SARS-CoV-2 lineage P.1 might escape neutralisation by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Continuous genomic surveillance of SARS-CoV-2 combined with antibody neutralisation assays could help to guide national immunisation programmes.
  • article 355 Citação(ões) na Scopus
    Evolution and epidemic spread of SARS-CoV-2 in Brazil
    (2020) CANDIDO, Darlan S.; CLARO, Ingra M.; JESUS, Jaqueline G. de; SOUZA, William M.; MOREIRA, Filipe R. R.; DELLICOUR, Simon; MELLAN, Thomas A.; PLESSIS, Louis du; PEREIRA, Rafael H. M.; SALES, Flavia C. S.; MANULI, Erika R.; THEZE, Julien; ALMEIDA, Luiz; MENEZES, Mariane T.; VOLOCH, Carolina M.; FUMAGALLI, Marcilio J.; COLETTI, Thais M.; SILVA, Camila A. M.; RAMUNDO, Mariana S.; AMORIM, Mariene R.; HOELTGEBAUM, Henrique H.; MISHRA, Swapnil; GILL, Mandev S.; CARVALHO, Luiz M.; BUSS, Lewis F.; JR, Carlos A. Prete; ASHWORTH, Jordan; I, Helder Nakaya; PEIXOTO, Pedro S.; BRADY, Oliver J.; NICHOLLS, Samuel M.; TANURI, Amilcar; ROSSI, Atila D.; V, Carlos K. Braga; GERBER, Alexandra L.; GUIMARAES, Ana Paula de C.; JR, Nelson Gaburo; ALENCAR, Cecila Salete; FERREIRA, Alessandro C. S.; LIMA, Cristiano X.; LEVI, Jose Eduardo; GRANATO, Celso; FERREIRA, Giulia M.; JR, Ronaldo S. Francisco; GRANJA, Fabiana; GARCIA, Marcia T.; MORETTI, Maria Luiza; JR, Mauricio W. Perroud; CASTINEIRAS, Terezinha M. P. P.; LAZARI, Carolina S.; HILL, Sarah C.; SANTOS, Andreza Aruska de Souza; SIMEONI, Camila L.; FORATO, Julia; SPOSITO, Andrei C.; SCHREIBER, Angelica Z.; SANTOS, Magnun N. N.; SA, Camila Zolini de; SOUZA, Renan P.; RESENDE-MOREIRA, Luciana C.; TEIXEIRA, Mauro M.; HUBNER, Josy; LEME, Patricia A. F.; MOREIRA, Rennan G.; NOGUEIRA, Mauricio L.; FERGUSON, Neil M.; COSTA, Silvia F.; PROENCA-MODENA, Jose Luiz; VASCONCELOS, Ana Tereza R.; BHATT, Samir; LEMEY, Philippe; WU, Chieh-Hsi; RAMBAUT, Andrew; LOMAN, Nick J.; AGUIAR, Renato S.; PYBUS, Oliver G.; SABINO, Ester C.; FARIA, Nuno Rodrigues
    Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. Because of limited available data, assessments of the impact of nonpharmaceutical interventions (NPIs) on this virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1 to 1.6 in Sao Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February and 11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average traveled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil and provides evidence that current interventions remain insufficient to keep virus transmission under control in this country.