Darlan da Silva Cândido

Imperial College London

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Nuno R. Faria

University of Oxford

ÉC

Éster Cerdeira Sabino

Universidade de São Paulo

Oliver G. Pybus

University of Oxford

Moritz U. G. Kraemer

University of Oxford

Ingra Morales Claro

Universidade de São Paulo

Renato Santana Aguiar

Universidade Federal de Minas Gerais

Jaqueline Góes de Jesus

Universidade de São Paulo

Flavia Cristina da Silva Sales

Universidade de São Paulo

Edécio Cunha‐Neto

Marqués de Valdecilla University Hospital

Ludmila Rodrigues Pinto Ferreira

Universidade Federal de Minas Gerais

Cooperative Institutions

Universidade de São Paulo

166

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

111

Fundação Oswaldo Cruz

102

University of Oxford

Universidade Federal de Minas Gerais

Imperial College London

Secretaria da Saúde

Ministério da Saúde

Universidade Federal do Ceará

Instituto do Coração

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Epidemiological and genomic investigation of chikungunya virus in Rio de Janeiro state, Brazil, between 2015 and 2018

medRxiv (Cold Spring Harbor Laboratory) (2023)

Filipe Romero Rebello Moreira Mariane Talon de Menezes Clarisse Salgado‐Benvindo Charles Whittaker Victoria Cox

Abstract Since 2014, Brazil has experienced an unprecedented epidemic caused by chikungunya virus (CHIKV), with several waves of East-Central-South-African (ECSA) lineage transmission reported across the country. In 2018, Rio de Janeiro state, the third most populous state in Brazil, reported 41% of all chikungunya cases in the country. Here we use evolutionary and epidemiological analysis to estimate the timescale of CHIKV-ECSA-American lineage and its epidemiological patterns in Rio de Janeiro. We show that the CHIKV-ECSA outbreak in Rio de Janeiro derived from two distinct clades introduced from the Northeast region in mid-2015 (clade RJ1, n = 63/67 genomes from Rio de Janeiro) and mid-2017 (clade RJ2, n = 4/67). We detected evidence for positive selection in non-structural proteins linked with viral replication in the RJ1 clade (clade-defining: nsP4-A481D) and the RJ2 clade (nsP1-D351G). Finally, we estimate the CHIKV-ECSA’s basic reproduction number ( R 0 ) to be between 1.2 to 1.6 and show that its instantaneous reproduction number ( R t ) displays a strong seasonal pattern with peaks in transmission coinciding with periods of high Aedes aegypti transmission potential. Our results highlight the need for continued genomic and epidemiological surveillance of CHIKV in Brazil, particularly during periods of high ecological suitability, and show that selective pressures underline the emergence and evolution of the large urban CHIKV-ECSA outbreak in Rio de Janeiro.

Lineage (genetic)

10.1101/2023.04.12.23288482

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Citations (0)

Circulation of chikungunya virus East/Central/South African lineage in Rio de Janeiro, Brazil

PLoS ONE (2019)

Joilson Xavier Marta Giovanetti Vagner Fonseca Julien Thézé Tiago Gräf

The emergence of chikungunya virus (CHIKV) has raised serious concerns due to the virus' rapid dissemination into new geographic areas and the clinical features associated with infection. To better understand CHIKV dynamics in Rio de Janeiro, we generated 11 near-complete genomes by means of real-time portable nanopore sequencing of virus isolates obtained directly from clinical samples. To better understand CHIKV dynamics in Rio de Janeiro, we generated 11 near-complete genomes by means of real-time portable nanopore sequencing of virus isolates obtained directly from clinical samples. Our phylogenetic reconstructions indicated the circulation of the East-Central-South-African (ECSA) lineage in Rio de Janeiro. Time-measured phylogenetic analysis combined with CHIKV notified case numbers revealed the ECSA lineage was introduced in Rio de Janeiro around June 2015 (95% Bayesian credible interval: May to July 2015) indicating the virus was circulating unnoticed for 5 months before the first reports of CHIKV autochthonous transmissions in Rio de Janeiro, in November 2015. These findings reinforce that continued genomic surveillance strategies are needed to assist in the monitoring and understanding of arbovirus epidemics, which might help to attenuate public health impact of infectious diseases.

Lineage (genetic)

Pandemic

Alphavirus infection

10.1371/journal.pone.0217871

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Citations (51)

Genomic epidemiology of SARS-CoV-2 transmission lineages in Ecuador

medRxiv (Cold Spring Harbor Laboratory) (2021)

Bernardo Gutiérrez Sully Márquez Belén Prado-Vivar Mónica Becerra-Wong Juan José Guadalupe

Abstract Characterisation of SARS-CoV-2 genetic diversity through space and time can reveal trends in virus importation and domestic circulation, and permit the exploration of questions regarding the early transmission dynamics. Here we present a detailed description of SARS-CoV-2 genomic epidemiology in Ecuador, one of the hardest hit countries during the early stages of the COVID-19 pandemic. We generate and analyse 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylgeographic analysis of these sequences in the context of global SARS-CoV-2 diversity enable us to identify and characterise individual transmission lineages within Ecuador, explore their spatiotemporal distributions, and consider their introduction and domestic circulation. Our results reveal a pattern of multiple international importations across the country, with apparent differences between key provinces. Transmission lineages were mostly introduced before the implementation of non-pharmaceutical interventions (NPIs), with differential degrees of persistence and national dissemination.

Pandemic

Molecular clock

10.1101/2021.03.31.21254685

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Citations (2)

Molecular characterization and sequecing analysis of SARS-CoV-2 genome in Minas Gerais, Brazil

Biologicals (2022)

Giulia Magalhães Ferreira Ingra Morales Claro Victória Riquena Grosche Darlan da Silva Cândido Diego Pandeló José

Pandemic

Coronavirus

Lineage (genetic)

Monophyly

10.1016/j.biologicals.2022.08.001

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Citations (2)

Dataset on SARS-CoV-2 non-pharmaceutical interventions in Brazilian municipalities

Scientific Data (2021)

Andreza Aruska de Souza Santos Darlan da Silva Cândido William Marciel de Souza Lewis Buss Sabrina L. Li

Abstract Brazil has one of the fastest-growing COVID-19 epidemics worldwide. Non-pharmaceutical interventions (NPIs) have been adopted at the municipal level with asynchronous actions taken across 5,568 municipalities and the Federal District. This paper systematises the fragmented information on NPIs reporting on a novel dataset with survey responses from 4,027 mayors, covering 72.3% of all municipalities in the country. This dataset responds to the urgency to track and share findings on fragmented policies during the COVID-19 pandemic. Quantifying NPIs can help to assess the role of interventions in reducing transmission. We offer spatial and temporal details for a range of measures aimed at implementing social distancing and the dates when these measures were relaxed by local governments.

Social distance

Pandemic

2019-20 coronavirus outbreak

10.1038/s41597-021-00859-1

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Citations (46)

SURTO HOSPITALAR DE COVID‐19 NUMA ÁREA ADMINISTRATIVA DO INSTITUTO CENTRAL DO HC‐FMUSP

The Brazilian Journal of Infectious Diseases (2021)

Thaís Guimarães Ícaro Boszczowski Ingra Morales Laína Bubach Carvalho Suely Luzia dos Santos

10.1016/j.bjid.2020.101065

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Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil

Nature Human Behaviour (2020)

William Marciel de Souza Lewis Buss Darlan da Silva Cândido Jean‐Paul Carrera Sabrina Li

Pandemic

10.1038/s41562-020-0928-4

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Citations (420)

Emergence and widespread circulation of a recombinant SARS-CoV-2 lineage in North America

medRxiv (Cold Spring Harbor Laboratory) (2021)

Bernardo Gutiérrez Hugo G. Castelán‐Sánchez Darlan da Silva Cândido Ben Jackson Shay Fleishon

Abstract Genetic recombination is an important driving force of coronavirus evolution. While some degree of virus recombination has been reported during the COVID-19 pandemic, previously detected recombinant lineages of SARS-CoV-2 have shown limited circulation and been observed only in restricted areas. Prompted by reports of unusual genetic similarities among several Pango lineages detected mainly in North and Central America, we present a detailed phylogenetic analysis of four SARS-CoV-2 lineages (B.1.627, B.1.628, B.1.631 and B.1.634) in order to investigate the possibility of virus recombination among them. Two of these lineages, B.1.628 and B.1.631, are split into two distinct clusters (here named major and minor ). Our phylogenetic and recombination analyses of these lineages find well-supported phylogenetic differences between the Orf1ab region and the rest of the genome (S protein and remaining reading frames). The lineages also contain several deletions in the NSP6, Orf3a and S proteins that can augment reconstruction of reliable evolutionary histories. By reconciling the deletions and phylogenetic data, we conclude that the B.1.628 major cluster originated from a recombination event between a B.1.631 major virus and a lineage B.1.634 virus. This scenario inferred from genetic data is supported by the spatial and temporal distribution of the three lineages, which all co-circulated in the USA and Mexico during 2021, suggesting this region is where the recombination event took place. We therefore support the designation of the B.1.628 major cluster as recombinant lineage XB in the Pango nomenclature. The widespread circulation of lineage XB across multiple countries over a longer timespan than the previously designated recombinant XA lineage raises important questions regarding the role and potential effects of recombination on the evolution of SARS-CoV-2 during the ongoing COVID-19 pandemic.

Lineage (genetic)

10.1101/2021.11.19.21266601

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Citations (10)

Blood Gene Signatures of Chagas Cardiomyopathy With or Without Ventricular Dysfunction

The Journal of Infectious Diseases (2016)

Ludmila Rodrigues Pinto Ferreira Frederico Moraes Ferreira Helder I. Nakaya Xutao Deng Darlan da Silva Cândido

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 7 million people in Latin American areas of endemicity. About 30% of infected patients will develop chronic Chagas cardiomyopathy (CCC), an inflammatory cardiomyopathy characterized by hypertrophy, fibrosis, and myocarditis. Further studies are necessary to understand the molecular mechanisms of disease progression. Transcriptome analysis has been increasingly used to identify molecular changes associated with disease outcomes. We thus assessed the whole-blood transcriptome of patients with Chagas disease. Microarray analysis was performed on blood samples from 150 subjects, of whom 30 were uninfected control patients and 120 had Chagas disease (1 group had asymptomatic disease, and 2 groups had CCC with either a preserved or reduced left ventricular ejection fraction [LVEF]). Each Chagas disease group displayed distinct gene expression and functional pathway profiles. The most different expression patterns were between CCC groups with a preserved or reduced LVEF. A more stringent analysis indicated that 27 differentially expressed genes, particularly those related to natural killer (NK)/CD8+ T-cell cytotoxicity, separated the 2 groups. NK/CD8+ T-cell cytotoxicity could play a role in determining Chagas disease progression. Understanding genes associated with disease may lead to improved insight into CCC pathogenesis and the identification of prognostic factors for CCC progression.

Chagas Disease

Pathogenesis

10.1093/infdis/jiw540

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Citations (43)

SARS-CoV-2 lineage-specific disease symptoms and disease severity in São Caetano do Sul city, Brazil

medRxiv (Cold Spring Harbor Laboratory) (2023)

Flavia Cristina da Silva Sales Carlos A. Prete Leandro Abade Lewis Buss Darlan da Silva Cândido

Abstract Background The city of São Caetano do Sul, Brazil, established a web-based platform to provide primary care to suspected COVID-19 patients, integrating clinical and demographic data and sample metadata. Here we describe lineage-specific spatiotemporal dynamics of infections, clinical symptoms, and disease severity during the first year of the epidemic. Methods We selected and sequenced 879 PCR+ swab samples (8% of all reported cases), obtaining a spatially and temporally representative set of sequences. Daily lineage-specific prevalence was estimating using a moving-window approach, allowing inference of cumulative cases and symptom probability stratified by lineage using integrated data from the platform. Results Most infections were caused by B.1.1.28 (41.3%), followed by Gamma (31.7%), Zeta (9.6%) and B1.1.33 (9.0%). Gamma and Zeta were associated with larger prevalence of dyspnoea (respectively 81.3% and 78.5%) and persistent fever (84.7% and 61.1%) compared to B.1.1.28 and B.1.1.33. Ageusia, anosmia, and coryza were respectively 18.9%, 20.3% and 17.8% less commonly caused by Gamma, while altered mental status was 108.9% more common in Zeta. Case incidence was spatially heterogeneous and larger in poorer and younger districts. Discussion Our study demonstrates that Gamma was associated with more severe disease, emphasising the role of its increased disease severity in the heightened mortality levels in Brazil.

Lineage (genetic)

Cumulative incidence

Anosmia

10.1101/2023.10.19.23297252

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