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    3 Aug 2022

    Spatial-temporal dynamics and recurrence of chikungunya virus in Brazil, MedRxiv, Read more

    Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused explosive epidemics linked to acute, chronic, and severe clinical outcomes. Since 2014, Brazil has had the highest number of chikungunya fever (CHIKF) cases in the Americas. Here, we report and contextualize the spatiotemporal dynamic of CHIKF in Brazil and combine genomic, epidemiological, and vector analyses to investigate CHIKF recurrence in several Brazilian states. From 2013 to 2022, CHIKV caused seven epidemic waves across Brazil, affecting 59.5% (3,316 of 5,570) of the country’s municipalities. To date, Ceará State in the northeast has been the most affected, with 81,274 cases during the two largest epidemic waves in 2016 and 2017, and the ongoing third wave in 2022. The 2022 CHIKF recurrence was associated with a new introduction of an East/Central/South African strain. Also, the CHIKV recurrences in Ceará, Tocantins, and Pernambuco States were limited to municipalities with few or no prior reported cases in the previous epidemic waves, suggesting that spatial heterogeneity of CHIKV spread and population immunity may explain the recurrence pattern in the country. In addition, the population density metrics of main CHIKV vector in Brazil, Ae. aegypti, were not correlated spatially with locations of CHIKF recurrence in Ceará and Tocantins States. Also, we show that CHIKF disproportionally affected females, and we estimated the case-fatality ratio in Ceará at ~1.3 deaths per 1,000 cases. These findings more comprehensively describe CHIKV epidemics in Brazil and contribute to understanding CHIKF recurrence in urban settings. Overall, this information may help guide public health policy to mitigate and reduce the burden of urban arboviruses.

    27 July 2022

    Tracking the Turnover of SARS-CoV-2 VOCs Gamma to Delta in a Brazilian State (Minas Gerais) with a high-vaccination status, Virus Evolution, Read more

    The emergence and global dissemination of SARS-CoV-2 variants of concern (VOC) have been described as the main factor driving the COVID-19 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed genotyping-PCR and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70% of the cases eight weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.

    20 June 2022

    Shotgun metagenomic sequencing of the first case of monkeypox virus in Brazil, 2022, Journal of the São Paulo Institute Tropical Medicine, Read more | Altmetric: 54

    Monkeypox virus (MPXV), a zoonotic virus endemic to the African continent, has been reported in 33 non-endemic countries since May 2022. We report an almost complete genome of the first confirmed case of MPXV in Brazil. Shotgun metagenomic sequencing was completed in 18 hours, from DNA extraction to consensus sequence generation.

    20 June 2022

    Emergence and widespread circulation of a recombinant SARS-CoV-2 lineage in North America, Cell Host & Microbe, Read more | Altmetric: 40

    Although recombination is a feature of coronavirus evolution, previously detected recombinant lineages of SARS-CoV-2 have shown limited circulation thus far. Here, we present a detailed phylogenetic analysis of four SARS-CoV-2 lineages to investigate the possibility of virus recombination among them. Our analyses reveal well-supported phylogenetic differences between the Orf1ab region encoding viral non-structural proteins and the rest of the genome, including Spike (S) protein and remaining reading frames. By accounting for several deletions in NSP6, Orf3a, and S, we conclude that the B.1.628 major cluster, now designated as lineage XB, originated from a recombination event between viruses of B.1.631 and B.1.634 lineages. This scenario is supported by the spatiotemporal distribution of these lineages across the USA and Mexico during 2021, suggesting that the recombination event originated in this geographical region. This event raises important questions regarding the role and potential effects of recombination on SARS-CoV-2 evolution.

    17 June 2022

    Predicting SARS-CoV-2 variant spread in a completely seropositive population using semi-quantitative antibody measurements in blood donors, Vaccines, Read more | Press: FAPESP and EurekaAlert AAAS | Altmetric: 99

    SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants which nears 100% in many settings. New analytic approaches are required to exploit the full information in serosurvey data. Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titres in serial cross-sectional monthly samples of routine blood donations across seven Brazilian state capitals (March 2021-November 2021). In an ecological analysis (unit of analysis: age-city-calendar month) we assessed the relative contributions of prior attack rate and vaccination to antibody titre in blood donors. We compared blood donor anti-S titre across the seven cities during the growth phase of the Delta variant of concern (VOC) and use this to predict the resulting age-standardized incidence of severe COVID-19 cases. On average we tested 780 samples per month in each location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven proximally by vaccination, mean antibody titre increased 16-fold over the study. The extent of prior natural infection shaped this process, with the greatest increases in antibody titres occurring in cities with the highest prior attack rates. Mean anti-S IgG was a strong predictor (adjusted R2 =0.89) of the number of severe cases caused by the Delta VOC in the seven cities. Semi-quantitative anti-S antibody titres are informative about prior exposure and vaccination coverage and can inform on the potential impact of future SARS-CoV-2 variants.

    18 May 2022

    Molecular and genomic investigation of an urban outbreak of dengue virus serotype 2 in Angola, 2017–2019, PLOS Neglected Tropical Diseases, Read more

    Angola has experienced dengue, yellow fever and Zika virus outbreaks between 2013–2017. To improve the detection of arbovirus outbreaks in Angola, we set up the National Arbovirus Laboratory of Surveillance Programme at the National Institute of Health Research (INIS), Ministry of Health, Angola, which officially kick-started arbovirus surveillance activities in early 2017. In this study we tested samples collected from patients with suspected dengue cases between January 2017 to February 2019. We report molecular and genomic findings on DENV2 transmission in Angola. On-site whole genome sequencing and subsequent phylogenetic analysis indicate a single introduction of the DENV2 Cosmopolitan genotype (also known as DENV2-II genotype) from Southern Asia, probably as a result of international travel, followed by moderate virus population growth. In Angola, most detections occurred in urban areas, although we detected DENV2 in 5 of the 18 provinces in Angola. This work emphasizes the importance of maintaining an active arbovirus surveillance programme throughout the country to investigate DENV transmission patterns and evaluate the risk of hyperendemicity in Angola.

    13 May 2022

    Clearance of Persistent SARS-CoV-2 RNA Detection in a NFkB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report, Viruses, Read more | Altmetric: 200

    Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

    14 May 2022

    Understanding Sabiá virus infections (Brazilian mammarenavirus), Travel Medicine and Infectious Disease, Read more | Altmetric: 40 

    Only two naturally occurring human Sabiá virus (SABV) infections have been reported, and those occurred over 20 years ago. We diagnosed two new cases of SABV infection using metagenomics in patients thought to have severe yellow fever and described new features of histopathological findings. We characterized clinical manifestations, histopathology and analyzed possible nosocomial transmission. Patients presented with hepatitis, bleeding, neurological alterations and died. We traced twenty-nine hospital contacts and evaluated them clinically and by RT-PCR and neutralizing antibodies. Autopsies uncovered unique features on electron microscopy, such as hepatocyte “pinewood knot” lesions. Although previous reports with similar New-World arenavirus had nosocomial transmission, our data did not find any case in contact tracing. Although an apparent by rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases had peculiar histopathological findings not previously described. The virological diagnosis was possible only by contemporary techniques such as metagenomic assays. We found no subsequent infections when we used serological and molecular tests to evaluate close contacts.

    10 May 2022

    Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals, Nature Medicine, Read more | Altmetric: 96

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil’s COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.

    14 April 2022

    Real-time RT-PCR for Venezuelan equine encephalitis complex, Madariaga and Eastern equine encephalitis viruses: application in clinical diagnostic and mosquito surveillance, Preprint, Read more

    The alphavirus encephalitis viruses include species of the Venezuelan equine encephalitis (VEE) complex, Maradiaga virus (MADV), and Eastern equine encephalitis virus (EEEV). They persist in sylvatic-enzootic cycles throughout the Americas and are transmitted to humans by Culex spp. mosquitoes. Human and equine outbreaks are reported sporadically in endemic regions. Detection of VEE complex, MADV and EEEV infections in the acute phase is complicated by their non-specific clinical manifestations and lack of widely available diagnostic tools. Current molecular tests lack optimal performance metrics characteristics necessary for routine diagnostic testing. Here we design two real-time RT-PCRs for VEE complex and MADV/EEEV, which were then evaluated by testing a set of clinical and mosquito samples collected during two outbreaks of VEEV and MADV in Panamá. The VEE complex and MADV/EEEV rRT-PCRs provide accurate detection while yielding significant benefits over currently available molecular methods.

    21 March 2022

    SARS-CoV-2 hospital-associated transmission dynamics in São Paulo, Brazil: a retrospective genomic surveillance study: Preprint, Read more

    Brazil reported its first SARS-CoV-2 case on 26 February 2020 in an international traveler returning to São Paulo, Brazil. By 10 June 2020, 3,898 healthcare workers (HCW) and patients at the Hospital das Clínicas (HC) in São Paulo, the largest hospital complex in Latin America, had tested positive for SARS-CoV-2 RNA. We aimed to provide insight into the transmission of SARS-CoV-2 in healthcare workers and patients, and within and between HC institutes during the early phase of the epidemic in Brazil.

    We analyzed epidemiological data from SARS-CoV-2 RT-PCR confirmed cases between 13 March to 10 June 2020. A total of 340 SARS-CoV-2 genomes were generated from healthcare workers and patients from two HC institutes not receiving COVID-19 patients (institutes A and C) and one institute receiving exclusively COVID-19 patients (institute B). Within- and between-institute transmission clusters were identified and within-cluster transmission dynamics was assessed using logistic regression analysis and a suite of phylogenetic genetic analyses.

    SARS-CoV-2 weekly incidence in healthcare workers was highest in institutes not receiving COVID-19 patients, and decreased by 75%, 54%, 48% for institutes C, A, B, respectively, after universal masking was adopted. We found a total of 86 hospital-acquired patient infections in HC during the study period, 81 4% (n=70) in institute C. Of these, 74.3% of these reported after mandatory universal masking. The average cluster size and cluster duration were larger in non-COVID institutes. Sequences from non-COVID institutes were more likely to cluster together than sequences from institute B (odds ratio, OR=4 17 and OR=3 48, for C and A institutes). The proportion of estimated viral importation events from outside the HC complex to the different HC institutes was highest for institute B (83 64%) compared to institute A (67 85%), and C (57 70%). The statistical support for virus migration from non-COVID institutes A and C to institute B was strong (Bayes factor = 113 7 and 84 4, respectively).

    The hospital-associated SARS-CoV-2 transmission was higher in non-COVID-19 healthcare institutes compared to a COVID-19 healthcare institute during the first epidemic wave in São Paulo, with our data supporting virus infection non-COVID-19 institutes as a source of infection in a COVID-19 institute, suggesting that risk perception and compliance was lower in non-COVID institutes.

    02 March 2022

    Measuring the effects of COVID-19-related disruption on dengue transmission in southeast Asia and Latin America: a statistical modelling study, The Lancet Infectious Diseases, Read more

    The COVID-19 pandemic has resulted in unprecedented disruption to society, which indirectly affects infectious disease dynamics. We aimed to assess the effects of COVID-19-related disruption on dengue, a major expanding acute public health threat, in southeast Asia and Latin America. We assembled data on monthly dengue incidence from WHO weekly reports, climatic data from ERA5, and population variables from WorldPop for 23 countries between January, 2014 and December, 2019 and fit a Bayesian regression model to explain and predict seasonal and multi-year dengue cycles. We compared model predictions with reported dengue data January to December, 2020, and assessed if deviations from projected incidence since March, 2020 are associated with specific public health and social measures (from the Oxford Coronavirus Government Response Tracer database) or human movement behaviours (as measured by Google mobility reports). We found a consistent, prolonged decline in dengue incidence across many dengue-endemic regions that began in March, 2020 (2·28 million cases in 2020 vs 4·08 million cases in 2019; a 44·1% decrease). We found a strong association between COVID-19-related disruption (as measured independently by public health and social measures and human movement behaviours) and reduced dengue risk, even after taking into account other drivers of dengue cycles including climatic and host immunity (relative risk 0·01–0·17, p<0·01). Measures related to the closure of schools and reduced time spent in non-residential areas had the strongest evidence of association with reduced dengue risk, but high collinearity between covariates made specific attribution challenging. Overall, we estimate that 0·72 million (95% CI 0·12–1·47) fewer dengue cases occurred in 2020 potentially attributable to COVID-19-related disruption.

    22 February 2022

    SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals, eLifeRead more | Altmetric: 103

    There are large differences in the shape and size of regional SARS-CoV-2 epidemics in Brazil. Here we tested monthly blood donation samples for IgG antibodies from March 2020 to March 2021 in eight of Brazil’s most populous cities. There was large variation in the inferred attack rate adjusted for seroreversion across cities, and seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate differed between cities and consistently increased with age. The infection hospitalisation rate (IHR) increased significantly during the gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system’s collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43–3.53). These results demonstrate large heterogeneity in epidemic spread and highlight the utility of blood donor serosurveillance to monitor SARS-CoV-2 epidemics.

    Editor’s evaluation

    This article describes a large and compelling COVID-19 sero-survey in Brazil that, when combined with death data, provides an estimate of the infection fatality ratio. This valuable study highlights both the strengths and challenges of blood donor sero-surveillance in a pandemic environment where multiple waves of infection occur and immune responses wane relatively quickly.

    05 February 2021

    Reinfection by the SARS-CoV-2 Gamma variant in blood donors in Manaus, Brazil, BMC Infectious Diseases, Read more | Altmetric: 34

    The city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by the Gamma variant during the second wave in Manaus and the protection conferred by previous infection, we analyzed a cohort of repeat blood donors to identify anti-SARS-CoV-2 antibody boosting as a means to infer reinfection.

    Reinfection due to Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics.

    7 January 2022

    Mapping environmental suitability of Haemagogus and Sabethes spp. mosquitoes to understand sylvatic transmission risk of yellow fever virus in Brazil, PLoS Neglected Tropical Diseases, Read more | Altmetric: 24

    Yellow fever virus (YFV) is an arbovirus transmitted to humans from mosquitoes and can lead to severe disease and death. Recent sporadic outbreaks coupled with low vaccination coverage have highlighted the importance of mosquito surveillance for preventing future outbreaks and potential virus spillover into dense urban areas. Yet, very little is known about the spatial distribution of mosquitoes known to transmit YFV and the factors that contribute to their environmental suitability in Brazil. We compiled an occurrence database of primary and secondary mosquito vectors belonging to Haemagogus and Sabethes species’ collected between 1991–2019 and integrated this data with environmental and land-use data to predict their spatial suitability at 1x1km resolution. Using this information, we identified suitable regions for their co-existence. We overlaid this information with human population density and locations of non-human primate host reservoirs to identify areas at risk of transmission and spillover. Our study provides high-resolution mapping tools to assist with mosquito and arbovirus surveillance which is especially useful in low-resource settings.

    29 December 2021

    Epidemiology of COVID-19 after Emergence of SARS-CoV-2 Gamma Variant, Brazilian Amazon, 2020–2021, Emerging Infectious Diseases – Dispatch, Read more

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant has been hypothesized to cause more severe illness than previous variants, especially in children. Successive SARS-CoV-2 IgG serosurveys in the Brazilian Amazon showed that age-specific attack rates and proportions of symptomatic SARS-CoV-2 infections were similar before and after Gamma variant emergence.

    09 December 2021

    Global disparities in SARS-CoV-2 genomic surveillance, Nature Communications, Read more | Altmetric: 156

    Collaboration with World Health Organization, Pan American Health Organization, and multiple sequencing initiatives across the globe.

    Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.

    09 December 2021

    Track Omicron’s spread with molecular data, Science, Read more | Almetric: 296

    On 26 November, the newly emerged variant Omicron was designated a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) (1). Rapid polymerase chain reaction (PCR) test results could improve estimates of the prevalence of Omicron around the world. The widely used Thermo Fisher TaqPath COVID-19 PCR assay was valuable in tracking the spread of the Alpha (B.1.1.7) VOC (2) because a deletion of amino acids 69 and 70 in Alpha’s spike gene (Δ69–70) yields a distinct absent S-gene (S) despite positive test results. The Delta VOC lacks this deletion and is therefore S-gene positive (S+) on TaqPath PCR tests (3). The Omicron VOC shares the spike Δ69–70 deletion with Alpha, which has dropped to negligible levels worldwide. Therefore, the frequency of S results can be used as a rapid proxy for the frequency of Omicron cases, provided initial detection of local circulation had been confirmed by sequencing.


    Photo: by Darlan Candido

    09 December 2021

    Tracking the emergence of disparities in the subnational spread of COVID-19 in Brazil using an online application for real-time data visualisation: a longitudinal analysis, The Lancet Regional Health- Americas, Read more | Altmetric: 19

    Brazil is one of the countries worst affected by the COVID-19 pandemic with over 20 million cases and 557,000 deaths reported by August 2021. Comparison of real-time local COVID-19 data between areas is essential for understanding transmission, measuring the effects of interventions, and predicting the course of the epidemic, but are often challenging due to different population sizes and structures. We describe the development of a new app for the real-time visualisation of COVID-19 data in Brazil at the municipality level. In the CLIC-Brazil app, daily updates of case and death data are downloaded, age standardised and used to estimate the effective reproduction number (Rt). We show how such platforms can perform real-time regression analyses to identify factors associated with the rate of initial spread and early reproduction number. We also use survival methods to predict the likelihood of occurrence of a new peak of COVID-19 incidence.

    21 September 2021

    Understanding the Potential Impact of Different Drug Properties on SARS-CoV-2 Transmission and Disease Burden: A Modeling Analysis, Clinical Infectious Diseases, Read more | Altmetric: 27

    The public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Using a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Advances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

    20 September 2021

    Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing, Preprint, Read more

    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 method 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, ‘SMART-9N’, and a version compatible with barcoded PCR primers available from Oxford Nanopore Technologies, ‘Rapid SMART-9N’, for the detection, characterization, and whole-genome sequencing of RNA viruses. 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 6e00 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.

    15 September 2021

    Scale-free dynamics of Covid-19 in a Brazilian city, Preprint, Read more

    Mathematical models can provide insights into the control of pandemic COVID-19, which remains a global priority. The dynamics of directly-transmitted infectious diseases, such as COVID-19, are usually described by compartmental models where individuals are classified as susceptible, infected and removed. These SIR models typically assume homogenous transmission of infection, even in large populations, a simplification that is convenient but inconsistent with observations. Here we use original data on the dynamics of COVID-19 spread in a Brazilian city to investigate the structure of the transmission network. We find that transmission can be described by a network in which each infectious individual has a small number of susceptible contacts, of the order of 2-5, which is independent of total population size. Compared with standard models of homogenous mixing, this scale-free, fractal infection process gives a better description of COVID-19 dynamics through time. In addition, the contact process explains the geographically localized clusters of disease seen in this Brazilian city. Our scale-free model can help refine criteria for physical and social distancing in order to more effectively mitigate the spread of COVID-19. We propose that scale-free COVID-19 dynamics could be a widespread phenomenon, a topic for further investigation.

    10 September 2021

    Altered demographic profile of hospitalizations during the second COVID-19 wave in Amazonas, Brazil, The Lancet Regional Health, Read more

    Recent months have seen the emergence of SARS-CoV-2 variants with altered epidemiological properties, including increased transmissibility and the ability to partially evade protection immunity from prior infection. These variants have frequently been associated with resurgence of transmission and COVID-19 mortality in settings where they have established. Detailed investigations into the epidemiology of variants of concern (VOC) are crucial to sustained, long-term control of SARS-CoV-2. Despite this, epidemiological studies remain scarce, particularly with regards to clinical outcomes and profiles of disease severity associated with VOC transmission.

    31 August 2021

    Paramyxoviruses from neotropical bats suggest a novel genus and nephrotropism, Infection, Genetics and Evolution, Read more

    Paramyxoviruses have a broad host range and geographic distribution, including human pathogens transmitted by bats, such as Nipah and Hendra viruses. In this study, we combined high-throughput sequencing and molecular approaches to investigate the presence of paramyxoviruses in neotropical bats (Microchiroptera suborder) in Brazil. We discovered and characterized three novel paramyxoviruses in the kidney tissues of apparently healthy common vampire bats (D. rotundus) and Seba’s short-tailed bats (C. perspicillata), which we tentatively named Kanhgág virus (KANV), Boe virus (BOEV), and Guató virus (GUATV). In this study, we classified these viruses as putative species into the Macrojêvirus genus, a newly proposed genus of the Orthoparamyxovirinae subfamily. Using RT-PCR, we detected these viruses in 20.9% (9 out of 43) of bats tested, and viral RNA was detected exclusively in kidney tissues. Attempts to isolate infectious virus were successful for KANV and GUATV. Our results expand the viral diversity, host range, and geographical distribution of the paramyxoviruses.

    9 July 2021

    Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection After Vaccination With Adenovirus-Vectored and Inactivated Vaccines: A Cohort Study, Viruses, Read more

    Some studies have determined that the SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination with adenovirus-vectored and inactivated vaccines. We analyzed epidemiological, clinical, and laboratory data from simultaneous COVID-19 outbreaks in a convent (Outbreak A) and in a long-term care facility (Outbreak B) in individuals vaccinated with a single dose of ChAdOx1 or two doses of the CoronaVac vaccine, respectively. First, we identified the viral lineages associated with these outbreaks by genome sequencing. Then, we assessed the relationship of viral load, specific immunoglobulin antibody levels, neutralization antibodies, case characteristics (age, vaccine type, and presence or absence of symptoms), and associations with risk of developing COVID-19.

    9 July 2021

    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, Lancet Microbe, Read more | Altmetric: 396

    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.  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. We found that 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.

    21 June 2021

    Brazil needs a coordinated and cooperative approach to tackle COVID-19, Nature Medicine, Read more | Altmetric: 42

    After more than 14 months under siege, Brazilians continue to suffer as they see thousands of people dying every day, killed by the fast-moving respiratory pathogen SARS-CoV-2. Families are struggling to secure their livelihoods, quell hunger and, in some cases, adjust to the long-term toll of having survived infection with SARS-CoV-2. With the surge in cases, overcrowding of hospitals and high lethality, those on the front lines understand that Brazil is at war with COVID-19. The assault has been brutal1. A quarter of all deaths from COVID-19 in Brazil were officially recorded in April 2021. Meanwhile, a SARS-CoV-2 variant of concern, lineage P.1 (B., continues to be detected in an ever-increasing share of infections, on the basis of the small number of genomes sequenced across the country. This Commentary discusses the many factors that explain why the toll of the pandemic on Brazil has been so extraordinary, including its close transport connectivity with world markets, the marked socioeconomic vulnerabilities of its many populations, and persistent inequities.

    17 June 2021

    Surveillance of hemorrhagic fever and/or neuroinvasive disease: challenges of diagnosis, Rev. Saúde Pública, Read more

    To evaluate the performance of post mortem laboratory analysis in identifying the causes of hemorrhagic fever and/or neuroinvasive disease in deaths by arbovirus infection. Retrospective cross-sectional study based on the differential analysis and final outcome obtained in patients whose samples underwent laboratory testing for arboviruses at the Pathology Center of the Adolfo Lutz Institute, in São Paulo, Brazil. Of the 1355 adults clinically diagnosed with hemorrhagic fever and/or neuroinvasive disease, the most commonly attributed cause of death and the most common final outcome was dengue fever. Almost half of the samples tested negative on all laboratory tests conducted. The failure to identify the causative agent in a great number of cases highlights a gap in the diagnosis of deaths of unknown etiology. Additional immunohistochemical and molecular assessments need to be added to the post-mortem protocol if all laboratory evaluations performed fail to identify a causative agent. While part of our findings may be due to technical issues related to sample fixation, better information availability when making the initial diagnosis is crucial. Including molecular approaches might lead to a significant advancement in diagnostic accuracy.

    15 June 2021

    Epidemiology and evolution of Zika virus in Minas Gerais, Southeast Brazil, Infection, Genetics and Evolution, Read more

    Autochthonous Zika virus (ZIKV) transmission in Brazil was first identified in April 2015 in Brazil, with the first ZIKV-associated microcephaly cases detected in October 2015. Despite efforts on understanding ZIKV transmission in Brazil, little is known about the virus epidemiology and genetic diversity in Minas Gerais (MG), the second-most populous state in the country. We report molecular and genomic findings from the main public health laboratory in MG. Until January 2020, 26,817 ZIKV suspected infections and 86 congenital syndrome cases were reported in MG state. We tested 8552 ZIKV and microcephaly suspected cases. Ten genomes were generated on-site directly from clinical samples. A total of 1723 confirmed cases were detected in Minas Gerais, with two main epidemic waves; the first and larger epidemic wave peaked in March 2016, with the second smaller wave that peaked in March 2017. Dated molecular clock analysis revealed that multiple introductions occurred in Minas Gerais between 2014 and 2015, suggesting that the virus was circulating unnoticed for at least 16 months before the first confirmed laboratory case that we retrospectively identified in December 2015. Our findings highlight the importance of continued genomic surveillance strategies combined with traditional epidemiology to assist public health laboratories in monitoring and understanding the diversity of circulating arboviruses, which might help attenuate the public health impact of infectious diseases.

    4 June 2021

    Genomic epidemiology of SARS-CoV-2 transmission lineages in Ecuador Virus Evolution Read more

    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 generated and analysed 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylogeographic 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.

    26 May 2021

    Epidemic Spread of SARS-CoV-2 Lineage B.1.1.7 in Brazil, Viruses, Read more

    The emergence of diverse lineages harboring mutations with functional significance and potentially enhanced transmissibility imposes an increased difficulty on the containment of the SARS-CoV-2 pandemic. In Brazil, six such lineages cocirculate, one originally from the UK (B.1.1.7), one original from South Africa (B.1.351), and four that emerged within different regions of the country, P.1 (Manaus), P.2 (Rio de Janeiro), N.9 (São Paulo), and N.10 (Maranhão). While reports on the spread of some of these lineages to other Brazilian regions exist, a single report on two cases of lineage B.1.1.7 in São Paulo has been published, and the extent of its geographic spread is currently unknown. Therefore, we conducted a genomic epidemiology study focused on characterizing the dissemination of this lineage in a national context.

    7 May 2021

    Multiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2, PLoS Biology, Read more | Altmetric: 159

    With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69–70, would cause a “spike gene target failure” (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69–70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675–3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675–3677 as the primary target and spike Δ69–70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1.

    06 May 2021

    Interacting Epidemics in Amazonian Brazil: Prior Dengue Infection Associated with Increased COVID-19 Risk in a Population-Based Cohort Study, Clinical Infectious Diseases, Read more

    Serologically proven prior dengue infection is associated with increased subsequent risk of clinically apparent COVID-19 in Amazonians, implying that sequential dengue and COVID-19 epidemics may impose an extra burden of disease to affected communities in the tropical and subtropical world.

    29 April 2021

    Higher risk of death from COVID-19 in low-income and non-White populations of São Paulo, Brazil, BMJ Global Health, Read more | Altmetric: 66

    Little evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in São Paulo state, Brazil, and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities. 

    25 April 2021

    Coronavirus from cities to forests: mapping vulnerable interfaces and hotspots for SARS-CoV-2 spillover from humans to biodiversityThe Lancet Planetary Health, Read more

    With the continuous spreading of SARS-CoV-2 globally, the probability for interactions between humans who are infected and wildlife tends to grow intensely, as well as the likelihood of viral spillover from humans to biodiversity. This aspect is of great concern for wildlife conservation and human health, because the list of highly susceptible animal groups that have contracted SARS-CoV-2 (bats, mustelids, and primates) is large and, once infected, these groups can act as vectors and reservoirs, becoming a substrate for viral mutations and recombinations and boosting the risk of new strains emerging, which can return to humans as new diseases. Little is known about the inducing factors facilitating coronavirus spillover from one species to another, but it can be argued that interface zones between wild fauna and humans, which are narrow edges between anthropic (cities, roads, parks, ecotourism sites, and agricultural frontiers) and sylvatic habitat, are zones of increased interaction between humans and wild animals, and thus have a higher probability of viral spillover events than other areas. In a similar context, the habitat compression by forest fragmentation also brings species and infected beings closer, reducing their home ranges and intensifying the risk of spillover among wild populations. Therefore, on the basis of the premise for zoonosis—the greater human–animal interaction, the greater risk of viral spillover—we aimed to identify the most and least susceptible areas to viral spillover in Brazil.

    25 April 2021

    Landscape connectivity for yellow fever: a proxy approach to detect displacement and circulation through environmental corridors and interfaces, The Lancet Public Health, Read more

    Yellow fever is an arboviral haemorrhagic disease transmitted by mosquitoes in the tropical regions of Africa and South America. WHO estimates that there are 200 000 severe cases and 30 000 deaths worldwide annually. In Brazil, the wild cycle of yellow fever (also termed urban cycle) occurs through transmission between non-human primates with infected mosquitoes of the Haemagogus and Sabethes genus as intermediaries. Serological analysis of deceased primates is the main monitoring method; however, in many cases, these primates die in remote zones, making the geographical monitoring of yellow fever occurrences difficult. Even so, zoonotic surveillance authorities have observed geographical patterns in yellow fever circulation, especially associated with the ecological connectivity between forest fragments with certain sizes and characteristics. However, several potential displacement corridors connecting geographical points with positive cases remain unknown. Unexpectedly, other routes apparently favourable to primate circulation appear to act as a barrier to yellow fever against displacement. The determination of landscape and ecological characteristics acting on this primate (and viral) circulation is essential for prediction and mapping of displacement corridors and susceptible zones, favouring decision making in planning preventive and proactive actions to combat yellow fever.

    19 April 2021

    Respiratory viral shedding in healthcare workers reinfected with SARS-CoV-2, Brazil, 2020, Emerging Infections Diseases, Read more

    We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non–variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.

    15 April 2021

    Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil , Published in Science, Read more | Altmetric: 2324

    Cases of 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 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 1.7–2.4-fold more transmissible, and that previous (non-P.1) infection provides 54–79% 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.

    8 April 2021

    Increasing frequency of SARS-CoV-2 lineages B.1.1.7, P.1 and P.2 and identification of a novel lineage harboring E484Q and N501T spike mutations in Minas Gerais, Southeast Brazil, Virological.org, Read more

    We report preliminary results of an ongoing investigation of SARS-CoV-2 genomic diversity in the metropolitan region of Belo Horizonte (MRBH), Minas Gerais, Brazil. We sequenced and characterized 85 nearly complete SARS-CoV-2 genome sequences from randomized samples collected between 28 October 2020 and 15 March 2021. Phylogenetic analysis reveals co-circulation of two variants of concern (VOC), B.1.1.7 (n=3, 3.53%) and P.1 (n=30, 35.29%), and variant of interest (VOI) P.2 (n=41, 48.23%). These variants harbor E484K (P.1 and P.2) and N501Y (P.1 and B.1.1.7) mutations that are associated with increased transmissibility or immune escape. The N501Y mutation has also been associated with an increase in COVID-19 hospitalizations and deaths. Notably, we find that between 28 Feb and 15 Mar, 68% of cases were caused by the P.1 lineage in the MRBH. In addition, we report a cluster of two sequences characterized by a unique array of 18 mutations, including new non-synonymous changes in the same critical spike amino acid positions, E484Q and N501T. This lineage seems to have emerged independently from the nationally widespread B.1.1.28, as previously reported for P.1 and P.2, and adds up to the composition of a complex epidemiological scenario of the SARS-CoV-2 pandemic in Brazil.

    6 April 2021

    SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil, Rev. Inst. Med. Trop. S. Paulo  Read more

    Reinfection by the severe acute respiratory syndrome coronavirus type 2 (SARS-COV-2) has been reported in many countries, suggesting that the virus may continue to circulate among humans despite the possibility of local herd immunity due to massive previous infections. The emergence of variants of concern (VOC) that are more transmissible than the previous circulating ones has raised particular concerns on the vaccines effectiveness and reinfection rates. The P.1 lineage was first identified in December 2020 in Manaus city and is now globally spread. We report the first case of reinfection of SARS-CoV-2 caused by the P.1 variant outside of Manaus. The potential of these new variants to escape naturally and vaccine- induced immunity highlights the need for a global vigilance.

    4 March 2021

    Dataset on SARS-CoV-2 non-pharmaceutical interventions in Brazilian municipalities, Published in Scientifica Data, Read more

    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.

    4 February 2021

    Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2 Wellcome Open Research Read more

    Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.
    Grinch combines this information and produces reports with descriptive tables and figures that can be found at https://cov-lineages.org/global_report.html

    27 January 2021

    Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence, The Lancet Read more | Altmetric: 8116

    Our latest comment on the resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence is out now in The Lancet. After initially containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many European and Asian countries had a resurgence of COVID-19 consistent with a large proportion of the population remaining susceptible to the virus after the first epidemic wave. By contrast, in Manaus, Brazil, a study of blood donors indicated that 76% (95% CI 67–98) of the population had been infected with SARS-CoV-2 by October, 2020.

    26 January 2021

    Local Transmission of SARS-CoV-2 Lineage B.1.1.7, Brazil, December 2020, Published in Emerging Infectious Diseases, Read more | Altmetric: 37

    In December 2020, research surveillance detected the B.1.1.7 lineage of severe acute respiratory syndrome coronavirus 2 in São 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.

    25 January 2021

    Increasing frequency of the P.1 lineage in Manaus Virological.org Read more

    We provide a brief report following up on our previous post.  Here we share a frequency table by date of collection for a total of 142 SARS-CoV-2 genome sequences from Manaus, including 115 partial, near-complete, and complete SARS-CoV-2 genome sequences generated by our team from samples collected in December 2020 (n=67, collection dates between 15 December 2020 and 31 December 2020) and January 2021 (n=48, collection dates between 1 Jan 2021 and 9 Jan 2021). Near-complete and complete sequences were classified using pangolin; partial sequences were typed using maximum likelihood phylogenetic analysis with an in-house dataset of near-complete or complete P.1, P.2, and B.1.1.28 sequences.

    21 January 2021

    Early Transmission Dynamics, Spread, and Genomic Characterization of SARS-CoV-2 in Panama, Emerging Infectious Diseases Read more

    We report an epidemiologic analysis of 4,210 cases of infection with severe acute respiratory syndrome coronavirus 2 and genetic analysis of 313 new near-complete virus genomes in Panama during March 9–April 16, 2020. Although containment measures reduced R0 and Rt, they did not interrupt virus spread in the country.

    12 January 2021

    Clinical features and natural history of the first 2073 suspected COVID-19 cases in the Corona São Caetano primary care programme: a prospective cohort study,  BMJ Open  Read More

    Despite most cases not requiring hospital care, there are limited community-based clinical data on COVID-19. The Corona São Caetano programme is a primary care initiative providing care to all residents with COVID-19 in São Caetano do Sul, Brazil. It was designed to capture standardised clinical data on community COVID-19 cases. After triage of potentially severe cases, consecutive patients presenting to a multimedia screening platform between 13 April and 13 May 2020 were tested at home with SARS-CoV-2 reverse transcriptase (RT) PCR; positive patients were followed up for 14 days with phone calls every 2 days. RT-PCR-negative patients were offered additional SARS-CoV-2 serology testing to establish their infection status. We describe the clinical, virological and natural history features of this prospective population-based cohort. Of 2073 suspected COVID-19 cases, 1583 (76.4%) were tested by RT-PCR, of whom 444 (28.0%, 95% CI 25.9 to 30.3) were positive; 604/1136 (53%) RT-PCR-negative patients underwent serology, of whom 52 (8.6%) tested SARS-CoV-2 seropositive. The most common symptoms of confirmed COVID-19 were cough, fatigue, myalgia and headache; whereas self-reported fever (OR 3.0, 95% CI 2.4 to 3.9), anosmia (OR 3.3, 95% CI 2.6 to 4.4) and ageusia (OR 2.9, 95% CI 2.3 to 3.8) were most strongly associated with a positive COVID-19 diagnosis by RT-PCR or serology. RT-PCR cycle thresholds were lower in men, older patients, those with fever and arthralgia and closer to symptom onset. The rates of hospitalisation and death among 444 RT-PCR-positive cases were 6.7% and 0.7%, respectively, with older age and obesity more frequent in the hospitalised group. COVID-19 presents in a similar way to other mild community-acquired respiratory diseases, but the presence of fever, anosmia and ageusia can assist the specific diagnosis. Most patients recovered without requiring hospitalisation with a low fatality rate compared with other hospital-based studies.

    12 January 2021

    Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings Virological.org Read more

    We have detected a new variant circulating in December in Manaus, Amazonas state, north Brazil, where very high attack rates have been estimated previously. The new lineage, named P.1 (descendent of B.1.1.28), contains a unique constellation of lineage defining mutations, including several mutations of known biological importance such as E484K, K417T, and N501Y. Importantly, the P.1 lineage was identified in 42% (13 out of 31) RT-PCR positive samples collected between 15 to 23 December, but it was absent in 26 publicly available genome surveillance samples collected in Manaus between March to November 2020. These findings indicate local transmission and possibly recent increase in the frequency of a new lineage from the Amazon region. The higher diversity and the earlier sampling dates of P.1. in Manaus corroborates the travel info of recently detected cases in Japan, suggesting the direction of travel was Manaus to Japan. The recent emergence of variants with multiple shared mutations in spike raises concern about convergent evolution to a new phenotype, potentially associated with an increase in transmissibility or propensity for re-infection of individuals.

    31 December 2020

    First report of the SARS-CoV-2 B.1.1.7 lineage in Brazil Emerging Infectious Diseases Read more

    We report the first two cases caused by the SARS-CoV-2 B.1.1.7 (also known as Variant of Concern 202012/01, VOC) lineage in Brazil. The findings come less than 36 hours upon sample collection. Samples were immediately analyzed using a portable DNA sequencer as part of genomic surveillance activities from the Brazil-UK CADDE project. Sequencing and phylogenetic analysis confirm two separate introductions of the VOC lineage in Brazil, possibly from the UK. One case reported no travel outside of Brazil. Given the higher transmissibility of the VOC compared to non-VOC lineages, increased genomic surveillance is urgently needed to investigate the extent of VOC circulation in the country.

    8 December 2020

    Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic, Science Read more | Altmetric: 5694

    SARS-CoV-2 spread rapidly in the Brazilian Amazon and the attack rate there is an estimate of the final size of a largely unmitigated epidemic. We use a convenience sample of blood donors to show that by June, one month after the epidemic peak in Manaus, capital of Amazonas state, 44% of the population had detectable IgG antibodies. Correcting for cases without a detectable antibody response and antibody waning, we estimate a 66% attack rate in June, rising to 76% in October. This is higher than in São Paulo, in southeastern Brazil, where the estimated attack rate in October is 29%. These results confirm that, when poorly controlled, COVID-19 can infect a high fraction of the population causing high mortality.

    03 November 2020

    A phylodynamic workflow to rapidly gain insights into the dispersal history and dynamics of SARS-CoV-2 lineages, Molecular Biology and Evolution Read more

    Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of SARS-CoV-2 have been generated and shared with the scientific community. The unparalleled volume of available genetic data presents a unique opportunity to gain real-time insights into the virus transmission during the pandemic, but also a daunting computational hurdle if analyzed with gold-standard phylogeographic approaches. To tackle this practical limitation, we here describe and apply a rapid analytical pipeline to analyze the spatio-temporal dispersal history and dynamics of SARS-CoV-2 lineages. As a proof of concept, we focus on the Belgian epidemic, which has had one of the highest spatial densities of available SARS-CoV-2 genomes. Our pipeline has the potential to be quickly applied to other countries or regions, with key benefits in complementing epidemiological analyses in assessing the impact of intervention measures or their progressive easement.

    4 September 2020

    Evolution and epidemic spread of SARS-CoV-2 in Brazil,  Science, Read more | Altmetric: 1095

    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 São 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.

    24 August 2020

    Subnational analysis of the COVID-19 epidemic in Brazil, Preprint, Read more

    Brazil is currently reporting the second highest number of COVID-19 deaths in the world. Here we characterise the initial dynamics of COVID-19 across the country and assess the impact of non-pharmaceutical interventions (NPIs) that were implemented using a semi-mechanistic Bayesian hierarchical modelling approach. Our results highlight the significant impact these NPIs had across states, reducing an average Rt > 3 to an average of 1.5 by 9-May-2020, but that these interventions failed to reduce Rt < 1, congruent with the worsening epidemic Brazil has experienced since. We identify extensive heterogeneity in the epidemic trajectory across Brazil, with the estimated number of days to reach 0.1% of the state population infected since the first nationally recorded case ranging from 20 days in São Paulo compared to 60 days in Goiás, underscoring the importance of sub-national analyses in understanding asynchronous state-level epidemics underlying the national spread and burden of COVID-19.

    7 August 2020

    Fatal outcome of chikungunya virus infection in Brazil, Clinical Infectious Diseases Read more

    A retrospective investigation was undertaken to describe clinical, epidemiological, and virus genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. Sera, cerebrospinal fluid (CSF), and tissue samples from 100 fatal cases with suspected arbovirus infection were tested for CHIKV, dengue (DENV), and Zika virus (ZIKV).  68 fatal cases had CHIKV infection confirmed by RT-qPCR (52.9%), viral antigen (41.1%), and/or specific-IgM (63.2%). Co-detection of CHIKV with DENV was found in 22% of fatal cases, ZIKV in 2.9%, and DENV and ZIKV in 1.5%. A total of 39 CHIKV-deaths presented with neurological signs and symptoms and CHIKV-RNA was found in the CSF of 92.3% of these patients. Fatal outcomes were associated with irreversible multiple organ dysfunction syndrome. Patients with diabetes appear to die at a higher frequency during the sub-acute phase. Genetic analysis showed the circulation of two CHIKV-East Central South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome.

    31 July 2020

    Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil, Nature Human Behaviour, Read more | Altmetric: 494

    The first case of COVID-19 was detected in Brazil on 25 February 2020. We report and contextualize epidemiological, demographic and clinical findings for COVID-19 cases during the first 3 months of the epidemic. By 31 May 2020, 514,200 COVID-19 cases, including 29,314 deaths, had been reported in 75.3% (4,196 of 5,570) of municipalities across all five administrative regions of Brazil. The R0 value for Brazil was estimated at 3.1 (95% Bayesian credible interval = 2.4–5.5), with a higher median but overlapping credible intervals compared with some other seriously affected countries. A positive association between higher per-capita income and COVID-19 diagnosis was identified. Furthermore, the severe acute respiratory infection cases with unknown aetiology were associated with lower per-capita income. Co-circulation of six respiratory viruses was detected but at very low levels. These findings provide a comprehensive description of the ongoing COVID-19 epidemic in Brazil and may help to guide subsequent measures to control virus transmission.

    10 July 2020

    Interfaces for spillover transmission for coronaviruses, Published in Estudos Avancados, Read more

    The current path of human development generates deleterious environmental impacts, which have a negative impact on health; among them, the intensified transmission of infectious diseases, epidemics, and pandemics, such as covid-19. The way we usually deal with biodiversity and ecosystems, combined with the effects of climate change, makes for interfaces and pathways that favor diversification, spillover, and the circulation of viruses. By these means, Sars-CoV-2 may invade Brazilian biomes, transforming, for instance, the Amazon rain forest into a huge reservoir from where coronavirus may return even more aggressive to health.

    25 Jul 2020

    Serial Interval Distribution of SARS-CoV-2 Infection in Brazil, Journal Travel Medicine, Read more

    Current assessments of SARS-CoV-2 transmission dynamics rely on accurate estimates of key epidemiological parameters, including the serial interval, which can be defined as the time between symptom onset of the source and the onset of symptoms of the recipient. We estimate the serial interval of SARS-CoV-2 from 65 infector–infectee pairs from Brazil.  The median serial interval in our data was estimated at 3 (standard deviation = 3.29) days.

    30 May 2020

    Genomic evidence of yellow fever virus in Aedes scapularis, southeastern Brazil, 2016, Acta Tropica Read more

    The southeastern region of Brazil has recently experienced the largest yellow fever disease outbreak in decades. Since July 2016 epizootic events were reported in São Paulo state’s north region, where 787 Culicidae were captured as part of public health surveillance efforts and tested using real-time quantitative PCR. One Aedes scapularis pool collected in November 2016 in an agriculture area in Urupês city tested positive for YFV-RNA. Using a validated multiplex PCR approach we were able to recover a complete virus genome sequence from this pool. Phylogenetic analysis of the novel strain and publicly available data indicates that the belongs to the South American genotype 1 clade circulating in Sao Paulo state and is basal to the recent outbreak clade in southeast Brazil. Our findings highlight the need of additional studies, including vector competence studies, to disentangle the role of Aedes scapularis in yellow fever transmission in the Americas.

    11 May 2020

    Importation and early local transmission of COVID-19 in Brazil, 2020, Revista Instituto Medicina Tropical, Read more

    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. Our study provides a snapshot of the early establishment of the COVID-19 pandemic in Brazil, characterized by multiple independent introductions from Italy, followed by local transmission of the virus in Sao Paulo. Phylogenetic analyses are broadly consistent with the patients’ self-reported traveling histories. We show that the two genomes associated with local transmission are linked to a patient infected in Italy and are identical to other Italian genomes collected in the same time window. Given the within-outbreak rate of evolutionary change estimated for SARS-CoV-2, we caution against inferring directionality of transmission based on genetic data alone. Such inferences can further be overshadowed by incomplete sampling due to delays, reflecting the lack of equitable access to diagnosis and genomic sequencing.

    15 March 2020

    Routes for COVID-19 importation in Brazil, Journal Travel Medicine, Read more

    To better understand the potential for SARS-CoV-2 introductions to Brazil, we estimate the relative risk of COVID-19 introduction to Brazilian cities by taking into account SARS-CoV-2 incidence per international traveller arriving at an airport in Brazil. We estimate that 54.8% of all imported cases would be expected to come from travellers infected in Italy and 9.3% and 8.3% of the cases would be from travellers infected in China and France, respectively. The route Italy–São Paulo was estimated to comprise 24.9% of total infected travellers flying to Brazil during this period. Moreover, we estimate that Italy has been the source location for five of the top 10 importation routes for infected travellers into Brazil based on the current epidemiological scenario. Consistent with this, at least 48% (n = 14/29) of the reported imported cases in Brazil have a history of travelling to Italy prior to the onset of symptoms, as of 9 March 2020. Six (23.1%) of the confirmed cases that acquired the virus in Italy have been identified in São Paulo.

    28 February 2020

    First cases of coronavirus disease (COVID-19) in Brazil, Virological, Read more

    We provide a brief report and phylogenetic analysis of the confirmed COVID-2 cases in Brazil. From 488 suspected cases, two have so far tested positive for COVID-19. These two cases both traveled to Northern Italy. Detailed clinical and epidemiological descriptions for suspected and confirmed patients, including for the two patients reported here, are available from the National Public Health Emergency Alert and Response Network from the Brazilian Ministry of Health. Full report available in Virological.org.

    7 August 2020

    Genomic Surveillance of Yellow Fever Virus Epidemic Waves in São Paulo, Brazil, 2016 – 2018, PLoS Pathogens, Read more

    Since July 2016, southeast Brazil has experienced the largest yellow fever virus (YFV) outbreak in decades. Using our validated portable sequencing protocols, we generated 46 complete novel YFV genomes and investigate the geographical and temporal distribution of observed cases in non-human primates in Sao Paulo state. We find that most cases in Sao Paulo result from a single introduction from Minas Gerais that spread at a rate of 1 km per day, consistent with a scenario of continued spread in non-human primate communities and sylvatic vector across forested patches, with occasional spillover to unvaccinated human populations.

    18 November 2019

    Early identification of dengue virus lineage replacement in Brazil using portable genomic surveillance, Preliminary report in Virological.org, Published in Mem Inst Oswaldo Cruz Read more

    This study uses portable sequencing validated protocols to rapidly generate the first virus genome data from 20 cases occurring in Araraquara and São José do Rio Preto, São Paulo state, Brazil. We find that the 2019 dengue outbreak in Brazil in this region is caused by a newly introduced DENV serotype 2 genotype III (Asian/American) that is replacing previously-circulating DENV2 lineages.

    14 February 2020

    The evolutionary dynamics of Oropouche Virus in South America, Journal of Virology, Read more

    The Amazon basin is host to numerous arthropod-borne viral pathogens that cause febrile disease in humans. Among these, Oropouche orthobunyavirus (OROV) is a relatively understudied member of the Peribunyavirales that causes periodic outbreaks in human populations in Brazil and other South American countries. Our results show that differing evolutionary processes on the three segments that encompass the viral genome of OROV lead to variable evolutionary rates and divergence dates that could be explained by cryptic reassortment. We also present the discovery of previously unobserved putative N-linked glycosylation sites and codons which evolve under positive selection on the viral surface proteins, and discuss the potential role of these features in the evolution of the virus through a combined phylogenetic and structural approach.

    31 January 2020

    Sabia virus infections in yellow fever suspected cases in Sao Paulo, Brazil Preliminary Report Read more

    We provide a brief report on two Sabia virus cases detected in Sao Paulo, Brazil, in December 2019. We used CADDE’s novel metagenomic protocol and design new PCR diagnostic primers and probes that can cover a larger diversity of SABV strains in Brazil. A preliminary report on our results can be found here.

    18 February 2020

    Genomic and Epidemiological Surveillance of Zika Virus in the Amazon Region, Cell Reports, Read more

    Zika virus (ZIKV) has caused an explosive epidemic linked to severe clinical outcomes in the Americas. As of June 2018, 4,929 ZIKV suspected infections and 46 congenital syndrome cases had been reported in Manaus, Amazonas, Brazil. Although Manaus is a key demographic hub in the Amazon region, little is known about the ZIKV epidemic there, in terms of both transmission and viral genetic diversity. Using portable virus genome sequencing, we generated 59 ZIKV genomes in Manaus. Phylogenetic analyses indicated multiple introductions of ZIKV from northeastern Brazil to Manaus. Spatial genomic analysis of virus movement among six areas in Manaus suggested that populous northern neighborhoods acted as sources of virus transmission to other neighborhoods. Our study revealed how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. These results might contribute to improving the public health response to outbreaks in Brazil.