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
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.
16 September 2021
Reinfection by the SARS-CoV-2 Gamma variant in blood donors in Manaus, Brazil, Preprint, Read more
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.
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.
08 September 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, Preprint, Read more
Brazil is one of the countries worst affected by the COVID-19 pandemic with over 20 million cases and 557,000 deaths reported. 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 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. After an initial introduction in São Paulo and Rio de Janeiro states in early March 2020, the epidemic spread to Northern states and then to highly populated coastal regions and the Central-West. Municipalities with higher metrics of social development experienced earlier arrival of COVID-19 (decrease of 11·1 days [95% CI:13·2,8·9] in the time to arrival for each 10% increase in the social development index). Differences in the initial epidemic intensity (mean Rt) were largely driven by geographic location and the date of local onset.
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.
26 August 2021
Global disparities in SARS-CoV-2 genomic surveillance, Preprint, Read more
The COVID-19 pandemic has revealed the importance of virus genome sequencing to guide public health interventions to control virus transmission and understand SARS-CoV-2 evolution. As of July 20th, 2021, >2 million SARS-CoV-2 genomes have been submitted to GISAID, 94% from high income and 6% from low and middle income countries. Here, we analyse the spatial and temporal heterogeneity in SARS-CoV-2 global genomic surveillance efforts. We report a comprehensive analysis of virus lineage diversity and genomic surveillance strategies adopted globally, and investigate their impact on the detection of known SARS-CoV-2 virus lineages and variants of concern. Our study provides a perspective on the global disparities surrounding SARS-CoV-2 genomic surveillance, their causes and consequences, and possible solutions to maximize the impact of pathogen genome sequencing for efforts on public health.
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
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
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.22.214.171.124), 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.
12 May 2021
Reinfection by the SARS-CoV-2 P.1 variant in blood donors in Manaus, Brazil, Preprint Read more
The city of Manaus, north Brazil, was stricken by a severe epidemic of SARS-Cov-2 in March 2020, reaching a seroprevalence of 76% by October 2020. Nevertheless, in late November an abrupt increase in hospitalizations and deaths hit Manaus, causing higher number of deaths compared to the first epidemic wave. It has been hypothesized that virus lineages circulating in the second wave, namely the P.1 variant of concern first detected in early December in Manaus, could be better at evading immunity generated in response to previous infection with other lineages. In order to estimate the reinfection rate during the resurgence of SARS-CoV-2 in Manaus, we tested serial samples from 238 unvaccinated repeat blood donors using a SARS-CoV-2 anti-N IgG chemiluminescence microparticle assay. Blood donors were divided into six groups that reflected the inferred sequence of infection and reinfection with non-P.1 and P.1 variants. We assumed that reinfections induce a recrudescence (or “boosting”) of plasma anti-N IgG antibody levels, yielding a V-shaped time series of antibody reactivity levels. We infer that 16.9% (95% CI [9.48%, 28.5%]) of all presumed P.1 infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections (defined by considering the time period when the antibody levels are expected to grow after recovery and the range of half-lives for antibody waning after seroconversion), these percentages increase respectively to 25.8% (95% CI [16.7%, 37.4%]), and 31.0% (95% CI [21.4%, 42.5%]). Our data suggest that reinfection due to P.1 is common and more frequent than what has been detected by traditional epidemiologic, molecular and genomic surveillance of clinical cases.
7 May 2021
Multiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2, PLoS Biology, Read more
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
25 April 2021
Coronavirus from cities to forests: mapping vulnerable interfaces and hotspots for SARS-CoV-2 spillover from humans to biodiversity, The 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
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
27 January 2021
Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence – Published in The Lancet Read more
26 January 2021
Local Transmission of SARS-CoV-2 Lineage B.1.1.7, Brazil, December 2020, Published in Emerging Infectious Diseases, Read more
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 Published in 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, Published in 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, Published in Science Read more
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, Published in 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, Published in Science, Read more
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, Published in 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
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
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.