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1.
Cell ; 185(3): 467-484.e15, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-35081335

RESUMEN

On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.

2.
Cell ; 184(11): 2939-2954.e9, 2021 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-33852911

RESUMEN

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Sitios de Unión , COVID-19/terapia , COVID-19/virología , Línea Celular , Humanos , Evasión Inmune , Inmunización Pasiva , Mutación , Unión Proteica , Dominios Proteicos , SARS-CoV-2/genética , Eliminación de Secuencia , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Vacunación , Vacunas/inmunología , Sueroterapia para COVID-19
3.
Cell ; 184(16): 4220-4236.e13, 2021 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-34242578

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone progressive change, with variants conferring advantage rapidly becoming dominant lineages, e.g., B.1.617. With apparent increased transmissibility, variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the United Kingdom. Here we study the ability of monoclonal antibodies and convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2, complement this with structural analyses of Fab/receptor binding domain (RBD) complexes, and map the antigenic space of current variants. Neutralization of both viruses is reduced compared with ancestral Wuhan-related strains, but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2, suggesting that individuals infected previously by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insights for immunization policy with future variant vaccines in non-immune populations.


Asunto(s)
Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/inmunología , SARS-CoV-2/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Complejo Antígeno-Anticuerpo/química , COVID-19/patología , COVID-19/terapia , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Chlorocebus aethiops , Cristalografía por Rayos X , Humanos , Inmunización Pasiva , Pruebas de Neutralización , Dominios Proteicos/inmunología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Células Vero , Sueroterapia para COVID-19
4.
PLoS Biol ; 20(8): e3001769, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35998195

RESUMEN

We propose a novel, non-discriminatory classification of monkeypox virus diversity. Together with the World Health Organization, we named three clades (I, IIa and IIb) in order of detection. Within IIb, the cause of the current global outbreak, we identified multiple lineages (A.1, A.2, A.1.1 and B.1) to support real-time genomic surveillance.


Asunto(s)
Monkeypox virus , Mpox , Brotes de Enfermedades , Genómica , Humanos , Mpox/diagnóstico , Mpox/epidemiología , Monkeypox virus/genética
5.
J Med Virol ; 96(3): e29551, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38506236

RESUMEN

Respiratory Syncytial Virus (RSV) is an important cause of respiratory infection in humans. Severe cases are common in children ≤2 years old, immunocompromised individuals, and the elderly. In 2020, RSV infection reduced in Rio Grande do Sul (RS), southern Brazil; however, in 2021 resurgence of RSV was observed. This study analyzed epidemiological and genetic features of RSV infection cases reported in 2021 in RS. Nasopharyngeal samples collected from individuals with respiratory infection negative for SARS-CoV-2, Influenza A and B viruses were assessed for the presence of RSV by real time RT-qPCR. RSV-A and RSV-B genomic sequencing and phylogenetic reconstructions were performed for genotyping and clade characterization. Among 21,035 respiratory samples analyzed, 2,947 were positive for RSV, 947 of which were hospitalized patients. Positive cases were detected year-round, with the highest number in June-July (winter). Children <1 year comprised 56.28% (n = 533) of the hospitalized patients infected with RSV, whereas 14.46% (n = 137) were individuals >60 years. Of a total of 361 deaths, 14.68% (n = 53) were RSV positive, mostly patients >60 years old (73.58%, n = 39). Chronic kidney disease, cardiopathy, Down syndrome and neurological diseases were associated with RSV infection. RSV-A was identified in 58.5% (n = 117/200) of the patients, and RSV-B in 41.5% (n = 83/200). Of 95 RSV genomes recovered from SARI cases, 66 were RSV-A GA.2.3.5 genotype, while 29 were RSV-B GB.5.0.5a genotype. This study provides epidemiological and molecular data on RSV cases in RS during the COVID-19 pandemic and highlights that investigation of different respiratory viruses is essential for decision-making and disease prevention and control measures.


Asunto(s)
COVID-19 , Gripe Humana , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Niño , Humanos , Lactante , Anciano , Preescolar , Persona de Mediana Edad , Virus Sincitial Respiratorio Humano/genética , Infecciones por Virus Sincitial Respiratorio/epidemiología , Filogenia , Brasil/epidemiología , Pandemias , COVID-19/epidemiología , SARS-CoV-2/genética , Gripe Humana/epidemiología
6.
J Infect Dis ; 228(12): 1680-1689, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-37571849

RESUMEN

This was a household-based prospective cohort study conducted in Rio de Janeiro, in which people with laboratory-confirmed coronavirus disease 2019 (COVID-19) and their household contacts were followed from April 2020 through June 2022. Ninety-eight reinfections were identified, with 71 (72.5%) confirmed by genomic analyses and lineage definition in both infections. During the pre-Omicron period, 1 dose of any COVID-19 vaccine was associated with a reduced risk of reinfection, but during the Omicron period not even booster vaccines had this effect. Most reinfections were asymptomatic or milder in comparison with primary infections, a justification for continuing active surveillance to detect infections in vaccinated individuals. Our findings demonstrated that vaccination may not prevent infection or reinfection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Therefore we highlight the need to continuously update the antigenic target of SARS CoV-2 vaccines and administer booster doses to the population regularly, a strategy well established in the development of vaccines for influenza immunization programs.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Prospectivos , Reinfección/epidemiología , Vacunas contra la COVID-19 , Brasil/epidemiología
8.
BMC Infect Dis ; 23(1): 295, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37147601

RESUMEN

BACKGROUND: While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening. METHODS: To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa coefficient were calculated to assess diagnostic performance. RESULTS: Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3-94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen's kappa value of 0.74 [95% confidence interval (CI): 0.67-0.81]. Sensitivity was 77% (95% CI: 70.9-82.2), specificity 95% (95% CI: 91.9-97), PPV 89.8% (95% CI: 83.1-94.4), NPV 87.9% (95% CI: 83.6-91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5-92)] with a Cohen's kappa value of 0.63 (95% CI: 0.35-0.91). CONCLUSIONS: Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant.


Asunto(s)
COVID-19 , Pacientes Ambulatorios , Adolescente , Adulto , Niño , Humanos , Saliva , Prueba de COVID-19 , SARS-CoV-2/genética , COVID-19/diagnóstico , Nasofaringe , Manejo de Especímenes
9.
Mem Inst Oswaldo Cruz ; 118: e230069, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37851721

RESUMEN

BACKGROUND: There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023. OBJECTIVES: The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19. METHODS: We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing. FINDINGS: The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue. MAIN CONCLUSIONS: This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.


Asunto(s)
COVID-19 , Femenino , Humanos , Anciano , COVID-19/complicaciones , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Brasil , Mapeo Cromosómico
10.
Mem Inst Oswaldo Cruz ; 117: e220155, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36700580

RESUMEN

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has become a major concern contributing to increased morbidity and mortality worldwide. OBJECTIVES: Here we describe the replacement of the Gamma variant of concern (VOC) with Delta in the western Brazilian Amazon. METHODS: In this study, we analysed 540 SARS-CoV-2 positive samples determined by qualitative real-time RT-PCR selected in the state of Rondônia between June and December 2021. The positive cohort was sequenced through next-generation sequencing (NGS) and each sample was quantified using real-time RT-qPCR, the whole genome sequence was obtained, SARS-CoV-2 lineages were classified using the system Pango and the maximum likelihood (ML) method was used to conduct phylogenetic analyses. FINDINGS: A total of 540 high-quality genomes were obtained, where the Delta VOC showed the highest prevalence making up 72%, with strain AY.43 being the most abundant, while the Gamma VOC was present in 28%, where the P.1 strain was the most frequent. In this study population, only 32.96% (178/540) had completed the vaccination schedule. MAIN CONCLUSIONS: This study highlighted the presence of Gamma and Delta variants of SARS-CoV-2 in RO. Furthermore, we observed the replacement of the Gamma VOC with the Delta VOC and its lineages.


Asunto(s)
COVID-19 , Humanos , Brasil/epidemiología , COVID-19/epidemiología , Filogenia , SARS-CoV-2/genética
11.
Analyst ; 147(24): 5613-5622, 2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36300735

RESUMEN

Two lineages (BA.1 and BA.2) of the Omicron variant are the main ones responsible for the recent COVID-19 pandemic waves worldwide. Monitoring the prevalence and spread of these variants is important as the presence of mutations might lower the efficacy of vaccines and hinder the benefits of monoclonal antibody therapies. Although the need to screen these new lineages is emerging, genetic sequencing is scarce due to its high cost. Alternatively, we propose using reverse transcription loop-mediated isothermal amplification (RT-LAMP) to infer the prevalence of these lineages and aid in genomic surveillance in countries with limited genetic sequencing capacity. For this, we designed specific primers and tested them on a panel of 267 sequenced RNA genomes from different lineages. The test for BA.1 and its descendants showed 96.63% sensitivity, 100% specificity, and 98.85% accuracy, and the test for BA.2 and descendants showed 90.00% sensitivity, 98.85% specificity, and 98.52% accuracy. These results demonstrate the potential of RT-LAMP to be an alternative to help monitor variants, especially in countries with scarce resources.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Colorimetría , Pandemias , COVID-19/diagnóstico , Técnicas de Amplificación de Ácido Nucleico
12.
Emerg Infect Dis ; 27(7): 1789-1794, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33883059

RESUMEN

A 37-year-old healthcare worker from the northeastern region of Brazil experienced 2 clinical episodes of coronavirus disease. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by reverse transcription PCR in samples collected 116 days apart. Whole-genome sequencing revealed that the 2 infections were caused by the most prevalent lineage in Brazil, B.1.1.33, and the emerging lineage P.2. The first infection occurred in June 2020; Bayesian analysis suggests reinfection at some point during September 14-October 11, 2020, a few days before the second episode of coronavirus disease. Of note, P.2 corresponds to an emergent viral lineage in Brazil that contains the mutation E484K in the spike protein. The P.2 lineage was initially detected in the state of Rio de Janeiro, and since then it has been found throughout the country. Our findings suggest not only a reinfection case but also geographic dissemination of the emerging Brazil clade P.2.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Teorema de Bayes , Brasil/epidemiología , Humanos , Reinfección
13.
Virol J ; 18(1): 222, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34789293

RESUMEN

BACKGROUND: We report a genomic surveillance of SARS-CoV-2 lineages circulating in Paraná, southern Brazil, from March 2020 to April 2021. Our analysis, based on 333 genomes, revealed that the first variants detected in the state of Paraná in March 2020 were the B.1.1.33 and B.1.1.28 variants. The variants B.1.1.28 and B.1.1.33 were predominant throughout 2020 until the introduction of the variant P.2 in August 2020 and a variant of concern (VOC), Gamma (P.1), in January 2021. The VOC Gamma, a ramification of the B.1.1.28 lineage first detected in Manaus (northern Brazil), has grown rapidly since December 2020 and was thought to be responsible for the deadly second wave of COVID-19 throughout Brazil. METHODS: The 333 genomic sequences of SARS-CoV-2 from March 2020 to April 2021 were generated as part of the genomic surveillance carried out by Fiocruz in Brazil Genomahcov Fiocruz. SARS-CoV-2 sequencing was performed using representative samples from all geographic areas of Paraná. Phylogenetic analyses were performed using the 333 genomes also included other SARS-CoV-2 genomes from the state of Paraná and other states in Brazil that were deposited in the GISAID. In addition, the time-scaled phylogenetic tree was constructed with up to 3 random sequences of the Gamma variant from each state in Brazil in each month of 2021. In this analysis we also added the sequences identified as the B.1.1.28 lineage of the Amazonas state and and the Gamma-like-II (P.1-like-II) lineage identified in different regions of Brazil. RESULTS: Phylogenetic analyses of the SARS-CoV-2 genomes that were previously classified as the VOC Gamma lineage by WHO/PANGO showed that some genomes from February to April 2021 branched in a monophyletic clade and that these samples grouped together with genomes recently described with the lineage Gamma-like-II. Additionally, a new mutation (E661D) in the spike (S) protein has been identified in nearly 10% of the genomes classified as the VOC Gamma from Paraná in March and April 2021.Finally, we analyzed the correlation between the lineage and the Gamma variant frequency, age group (patients younger or older than 60 years old) and the clinical data of 86 cases from the state of Paraná. CONCLUSIONS: Our results provided a reliable picture of the evolution of the SARS-CoV-2 pandemic in the state of Paraná characterized by the dominance of the Gamma strain, as well as a high frequencies of the Gamma-like-II lineage and the S:E661D mutation. Epidemiological and genomic surveillance efforts should be continued to unveil the biological relevance of the novel mutations detected in the VOC Gamma in Paraná.


Asunto(s)
COVID-19/virología , SARS-CoV-2 , Brasil/epidemiología , COVID-19/epidemiología , Brotes de Enfermedades , Humanos , Persona de Mediana Edad , Mutación , Filogenia , Vigilancia de la Población , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Secuenciación Completa del Genoma
14.
Mem Inst Oswaldo Cruz ; 116: e200443, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33566951

RESUMEN

BACKGROUND: The coronaviruses (CoVs) called the attention of the world for causing outbreaks of severe acute respiratory syndrome (SARS-CoV), in Asia in 2002-03, and respiratory disease in the Middle East (MERS-CoV), in 2012. In December 2019, yet again a new coronavirus (SARS-CoV-2) first identified in Wuhan, China, was associated with a severe respiratory infection, known today as COVID-19. This new virus quickly spread throughout China and 30 additional countries. As result, the World Health Organization (WHO) elevated the status of the COVID-19 outbreak from emergency of international concern to pandemic on March 11, 2020. The impact of COVID-19 on public health and economy fueled a worldwide race to approve therapeutic and prophylactic agents, but so far, there are no specific antiviral drugs or vaccines available. In current scenario, the development of in vitro systems for viral mass production and for testing antiviral and vaccine candidates proves to be an urgent matter. OBJECTIVE: The objective of this paper is study the biology of SARS-CoV-2 in Vero-E6 cells at the ultrastructural level. METHODS: In this study, we documented, by transmission electron microscopy and real-time reverse transcription polymerase chain reaction (RT-PCR), the infection of Vero-E6 cells with SARS-CoV-2 samples isolated from Brazilian patients. FINDINGS: The infected cells presented cytopathic effects and SARS-CoV-2 particles were observed attached to the cell surface and inside cytoplasmic vesicles. The entry of the virus into cells occurred through the endocytic pathway or by fusion of the viral envelope with the cell membrane. Assembled nucleocapsids were verified inside rough endoplasmic reticulum cisterns (RER). Viral maturation seemed to occur by budding of viral particles from the RER into smooth membrane vesicles. MAIN CONCLUSIONS: Therefore, the susceptibility of Vero-E6 cells to SARS-CoV-2 infection and the viral pathway inside the cells were demonstrated by ultrastructural analysis.


Asunto(s)
Efecto Citopatogénico Viral , Vesículas Citoplasmáticas/virología , SARS-CoV-2/fisiología , Células Vero/virología , Animales , Chlorocebus aethiops , Endocitosis , Retículo Endoplásmico/virología , Humanos , Microscopía Electrónica de Transmisión , Nucleocápside , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Internalización del Virus
15.
J Clin Microbiol ; 57(12)2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31554673

RESUMEN

In this work, we describe a SYBR-Green one-step reverse transcription-PCR protocol coupled with a melting temperature analysis (RT-PCR-Tm ), which allows the discrimination of influenza B lineages Yamagata and Victoria. The assay is performed using a regular real-time thermocycler and is based on differences in melting temperature (Tm ) of a 131-bp amplicon, obtained from a conserved region of hemagglutinin gene. A total of 410 samples collected during the 2004, 2008, and 2010-2017 influenza seasons in Brazil were tested, and the lineages were correctly characterized using their melting profiles. The temperature range is significantly different between both lineages throughout the time (Mann-Whitney test; P < 0.0001, confidence interval = 95%), and the Tm is not affected by viral load (Spearman correlation test; r = 0.287, P = 2.245 × 10-9). The simplicity and cost-effectiveness of this protocol make it an option for influenza B lineage surveillance worldwide.


Asunto(s)
Virus de la Influenza B/clasificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/diagnóstico , Desnaturalización de Ácido Nucleico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Brasil , Costos y Análisis de Costo , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Virus de la Influenza B/genética , Gripe Humana/virología , Reacción en Cadena en Tiempo Real de la Polimerasa/economía , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/economía , Factores de Tiempo
16.
Emerg Infect Dis ; 23(1): 152-154, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27983507
17.
Mem Inst Oswaldo Cruz ; 110(1): 148-50, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25742277

RESUMEN

The influenza A(H3N2) virus has circulated worldwide for almost five decades and is the dominant subtype in most seasonal influenza epidemics, as occurred in the 2014 season in South America. In this study we evaluate five whole genome sequences of influenza A(H3N2) viruses detected in patients with mild illness collected from January-March 2014. To sequence the genomes, a new generation sequencing (NGS) protocol was performed using the Ion Torrent PGM platform. In addition to analysing the common genes, haemagglutinin, neuraminidase and matrix, our work also comprised internal genes. This was the first report of a whole genome analysis with Brazilian influenza A(H3N2) samples. Considerable amino acid variability was encountered in all gene segments, demonstrating the importance of studying the internal genes. NGS of whole genomes in this study will facilitate deeper virus characterisation, contributing to the improvement of influenza strain surveillance in Brazil.


Asunto(s)
Brotes de Enfermedades , Genoma Viral , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/virología , ARN Viral/aislamiento & purificación , Brasil/epidemiología , Humanos , Gripe Humana/epidemiología , Análisis de Secuencia de ARN/métodos , Índice de Severidad de la Enfermedad
18.
Mem Inst Oswaldo Cruz ; 110(1): 101-5, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25742269

RESUMEN

The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA) inhibitor oseltamivir (OST). Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated individuals. To spread in community settings, H275Y mutants must contain additional mutations, collectively called permissive mutations. We display the permissive mutations in NA of OST-resistant A(H1N1)pdm09 virus found in Brazilian community settings. The NAs from 2013 are phylogenetically distinct from those of 2012, indicating a tendency of positive selection of NAs with better fitness. Some previously predicted permissive mutations, such as V241I and N369K, found in different countries, were also detected in Brazil. Importantly, the change D344N, also predicted to compensate loss of fitness imposed by H275Y mutation, was found in Brazil, but not in other countries in 2013. Our results reinforce the notion that OST-resistant A(H1N1)pdm09 strains with compensatory mutations may arise in an independent fashion, with samples being identified in different states of Brazil and in different countries. Systematic circulation of these viral strains may jeopardise the use of the first line of anti-influenza drugs in the future.


Asunto(s)
Antivirales/uso terapéutico , Farmacorresistencia Viral/genética , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/virología , Mutación , Oseltamivir/uso terapéutico , Adulto , Brasil , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Gripe Humana/tratamiento farmacológico , Tasa de Mutación , Líquido del Lavado Nasal/virología , Neuraminidasa/genética , Filogenia , Filogeografía , ARN Viral/aislamiento & purificación
19.
Mem Inst Oswaldo Cruz ; 109(7): 912-7, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25410995

RESUMEN

After the World Health Organization officially declared the end of the first pandemic of the XXI century in August 2010, the influenza A(H1N1)pdm09 virus has been disseminated in the human population. In spite of its sustained circulation, very little on phylogenetic data or oseltamivir (OST) resistance is available for the virus in equatorial regions of South America. In order to shed more light on this topic, we analysed the haemagglutinin (HA) and neuraminidase (NA) genes of influenza A(H1N1)pdm09 positive samples collected during the pandemic period in the Pernambuco (PE), a northeastern Brazilian state. Complete HA sequences were compared and amino acid changes were related to clinical outcome. In addition, the H275Y substitution in NA, associated with OST resistance, was investigated by pyrosequencing. Samples from PE were grouped in phylogenetic clades 6 and 7, being clustered together with sequences from South and Southeast Brazil. The D222N/G HA gene mutation, associated with severity, was found in one deceased patient that was pregnant. Additionally, the HA mutation K308E, which appeared in Brazil in 2010 and was only detected worldwide the following year, was identified in samples from hospitalised cases. The resistance marker H275Y was not identified in samples tested. However, broader studies are needed to establish the real frequency of resistance in this Brazilian region.


Asunto(s)
Hemaglutininas/genética , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Neuraminidasa/genética , Pandemias , Antivirales/uso terapéutico , Biomarcadores/análisis , Brasil/epidemiología , Farmacorresistencia Viral/fisiología , Femenino , Frecuencia de los Genes/genética , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/virología , Mutación/genética , Oseltamivir/uso terapéutico , Filogenia , Embarazo , ARN Viral/análisis , Análisis de Secuencia de ADN/métodos , Virulencia , Factores de Virulencia/genética
20.
Microbiol Spectr ; 12(3): e0383123, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38315011

RESUMEN

The SARS-CoV-2 XBB is a group of highly immune-evasive lineages of the Omicron variant of concern that emerged by recombining BA.2-descendent lineages and spread worldwide during 2023. In this study, we combine SARS-CoV-2 genomic data (n = 11,065 sequences) with epidemiological data of severe acute respiratory infection (SARI) cases collected in Brazil between October 2022 and July 2023 to reconstruct the space-time dynamics and epidemiologic impact of XBB dissemination in the country. Our analyses revealed that the introduction and local emergence of lineages carrying convergent mutations within the Spike protein, especially F486P, F456L, and L455F, propelled the spread of XBB* lineages in Brazil. The average relative instantaneous reproduction numbers of XBB* + F486P, XBB* + F486P + F456L, and XBB* + F486P + F456L + L455F lineages in Brazil were estimated to be 1.24, 1.33, and 1.48 higher than that of other co-circulating lineages (mainly BQ.1*/BE*), respectively. Despite such a growth advantage, the dissemination of these XBB* lineages had a reduced impact on Brazil's epidemiological scenario concerning previous Omicron subvariants. The peak number of SARI cases from SARS-CoV-2 during the XBB wave was approximately 90%, 80%, and 70% lower than that observed during the previous BA.1*, BA.5*, and BQ.1* waves, respectively. These findings revealed the emergence of multiple XBB lineages with progressively increasing growth advantage, yet with relatively limited epidemiological impact in Brazil throughout 2023. The XBB* + F486P + F456L + L455F lineages stand out for their heightened transmissibility, warranting close monitoring in the months ahead. IMPORTANCE: Brazil was one the most affected countries by the SARS-CoV-2 pandemic, with more than 700,000 deaths by mid-2023. This study reconstructs the dissemination of the virus in the country in the first half of 2023, a period characterized by the dissemination of descendants of XBB.1, a recombinant of Omicron BA.2 lineages evolved in late 2022. The analysis supports that XBB dissemination was marked by the continuous emergence of indigenous lineages bearing similar mutations in key sites of their Spike protein, a process followed by continuous increments in transmissibility, and without repercussions in the incidence of severe cases. Thus, the results suggest that the epidemiological impact of the spread of a SARS-CoV-2 variant is influenced by an intricate interplay of factors that extend beyond the virus's transmissibility alone. The study also underlines the need for SARS-CoV-2 genomic surveillance that allows the monitoring of its ever-shifting composition.


Asunto(s)
COVID-19 , Humanos , Brasil/epidemiología , COVID-19/epidemiología , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética
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