Imperial College London

Professor Nuno R. Faria

Faculty of MedicineSchool of Public Health

Professor in Virus Genomic Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3560n.faria

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

212 results found

Claro IM, Romano CM, Candido DDS, Lima ELD, Lindoso JAL, Ramundo MS, Moreira FRR, Barra LAC, Borges LMS, Medeiros LA, Tomishige MYS, Moutinho T, Silva AJDD, Rodrigues CCM, Azevedo LCFD, Villas-Boas LS, Silva CAMD, Coletti TM, Manuli ER, O'Toole A, Quick J, Loman N, Rambaut A, Faria NR, Figueiredo-Mello C, Sabino ECet al., 2022, Shotgun metagenomic sequencing of the first case of monkeypox virus in Brazil, 2022., Revista do Instituto de Medicina Tropical de São Paulo, Vol: 64, Pages: 1-4, ISSN: 0036-4665

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.

Journal article

Neto Z, Martinez PA, Hill SC, Jandondo D, Thézé J, Mirandela M, Aguiar RS, Xavier J, Dos Santos Sebastião C, Cândido ALM, Vaz F, Castro GR, Paixão JP, Loman NJ, Lemey P, Pybus OG, Vasconcelos J, Faria NR, de Morais Jet al., 2022, Molecular and genomic investigation of an urban outbreak of dengue virus serotype 2 in Angola, 2017-2019, PLoS Neglected Tropical Diseases, Vol: 16, ISSN: 1935-2727

BACKGROUND: The transmission patterns and genetic diversity of dengue virus (DENV) circulating in Africa remain poorly understood. Circulation of the DENV serotype 1 (DENV1) in Angola was detected in 2013, while DENV serotype 2 (DENV2) was detected in 2018. Here, we report results from molecular and genomic investigations conducted at the Ministry of Health national reference laboratory (INIS) in Angola on suspected dengue cases detected between January 2017 and February 2019. METHODS: A total of 401 serum samples from dengue suspected cases were collected in 13 of the 18 provinces in Angola. Of those, 351 samples had complete data for demographic and epidemiological analysis, including age, gender, province, type of residence, clinical symptoms, as well as dates of onset of symptoms and sample collection. RNA was extracted from residual samples and tested for DENV-RNA using two distinct real time RT-PCR protocols. On-site whole genome nanopore sequencing was performed on RT-PCR+ samples. Bayesian coalescent models were used to estimate date and origin of outbreak emergence, as well as population growth rates. RESULTS: Molecular screening showed that 66 out of 351 (19%) suspected cases were DENV-RNA positive across 5 provinces in Angola. DENV RT-PCR+ cases were detected more frequently in urban sites compared to rural sites. Of the DENV RT-PCR+ cases most were collected within 6 days of symptom onset. 93% of infections were confirmed by serotype-specific RT-PCR as DENV2 and 1 case (1.4%) was confirmed as DENV1. Six CHIKV RT-PCR+ cases were also detected during the study period, including 1 co-infection of CHIKV with DENV1. Most cases (87%) were detected in Luanda during the rainy season between April and October. Symptoms associated with severe dengue were observed in 11 patients, including 2 with a fatal outcome. On-site nanopore genome sequencing followed by genetic analysis revealed an introduction of DENV2 Cosmopolitan genotype (also known as DENV2-II genotype)

Journal article

Sabino JS, Amorim MR, de Souza WM, Marega LF, Mofatto LS, Toledo-Teixeira DA, Forato J, Stabeli RG, Costa ML, Spilki FR, Sabino EC, Faria NR, Benites BD, Addas-Carvalho M, Stucchi RSB, Vasconcelos DM, Weaver SC, Granja F, Proenca-Modena JL, Vilela MMDSet al., 2022, Clearance of persistent SARS-CoV-2 RNA detection in a NF kappa B-Deficient patient in association with the ingestion of human breast milk: a case report, Viruses-Basel, Vol: 14, ISSN: 1999-4915

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

Journal article

Brizzi A, Whittaker C, Servo LMS, Hawryluk I, Prete Jr CA, de Souza WM, Aguiar RS, Araujo LJT, Bastos LS, Blenkinsop A, Buss LF, Candido D, Castro M, Costa S, Croda J, de Souza Santos AA, Dye C, Flaxman S, Fonseca PLC, Geddes VEV, Gutierrez B, Lemey P, Levin AS, Mellan T, Bonfim D, Miscoridou X, Mishra S, Monod M, Moreira FRR, Ranzani O, Schnekenberg R, Semenova E, Sonnabend R, Souza RP, Xi X, Sabino E, Faria NR, Bhatt S, Ratmann Oet al., 2022, Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals, Nature Medicine, Vol: 28, ISSN: 1078-8956

The SARS-CoV-2 Gamma variant of concern spread rapidly across Brazil since late 2020, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed Gamma’s spread across 14 state capitals, during which typically more than half of hospitalised patients aged 70 and over died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed prior to detection of Gamma. Using a Bayesian fatality rate model, we find 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.

Journal article

Nastri AC, Duarte-Neto AN, Casadio LVB, Souza WMD, Claro IM, Manuli ER, Selegatto G, Saloma MC, Fialkovitz G, Taborda M, Almeida BLD, Magri MC, Guedes AR, Neto LVP, Sataki FM, Guimaraes T, Mendes-Correa MC, Tozetto-Mendoza TR, Fumagalli MJ, Ho Y-L, Silva CAMD, Coletti TM, Jesus JGD, Romano CM, Hill SC, Pybus O, Pinho JRR, Ledesma FL, Casal YR, Kanamura C, Araujo LJTD, Ferreira CSDS, Guerra JM, Figueiredo LTM, Dolhnikoff M, Faria NR, Sabino EC, Avancini V, Alves F, Levin ASet al., 2022, Understanding Sabia virus infections<i> (Brazilian</i><i> mammarenavirus)</i>, TRAVEL MEDICINE AND INFECTIOUS DISEASE, Vol: 48, ISSN: 1477-8939

Journal article

Jing X, Xu M, Song D, Yue T, Wang Y, Zhang P, Zhong Y, Zhang M, Lam TT-Y, Faria NR, De Clercq E, Li Get al., 2022, Association between inflammatory cytokines and anti-SARS-CoV-2 antibodies in hospitalized patients with COVID-19, Immunity and Ageing, Vol: 19, Pages: 1-17, ISSN: 1742-4933

BackgroundCOVID-19 patients may experience “cytokine storm” when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies.MethodsThis retrospective study enrolled a cohort of 272 hospitalized patients with laboratory-confirmed SARS-CoV-2. Laboratory assessments of serum cytokines (IL-2R, IL-6, IL-8, IL-10, TNF-α), anti-SARS-CoV-2 IgG/IgM antibodies, and peripheral blood biomarkers were conducted during hospitalization.ResultsAt hospital admission, 36.4% patients were severely ill, 51.5% patients were ≥ 65 years, and 60.3% patients had comorbidities. Higher levels of IL-2R and IL-6 were observed in older patients (≥65 years). Significant differences of IL-2R (week 2 to week ≥5 from symptom onset), IL-6 (week 1 to week ≥5), IL-8 (week 2 to week ≥5), and IL-10 (week 1 to week 3) were observed between moderately-ill and severely ill patients. Anti-SARS-CoV-2 IgG titers were significantly higher in severely ill patients than in moderately ill patients, but such difference was not observed for IgM. High titers of early-stage IL-6, IL-8, and TNF-α (≤2 weeks after symptom onset) were positively correlated with high titers of late-stage IgG (≥5 weeks after symptom onset). Deaths were mostly observed in severely ill older patients (45.9%). Survival analyses revealed risk factors of patient age, baseline COVID-19 severity, and baseline IL-6 that affected survival time, especially in severely ill older patients.ConclusionEarly responses of elevated cytokines such as IL-6 reflect the active immune responses, leading to high titers of IgG antibodies against COVID-19.

Journal article

Nicolete VC, Rodrigues PT, Fernandes ARJ, Corder RM, Tonini J, Buss LF, Sales FC, Faria NR, Sabino EC, Castro MC, Ferreira MUet al., 2022, Epidemiology of COVID-19 after emergence of SARS-CoV-2 gamma variant, Brazilian Amazon, 2020-2021, Emerging Infectious Diseases, Vol: 28, Pages: 709-712, ISSN: 1080-6040

he 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.

Journal article

Prete CA, Buss LF, Buccheri R, Abrahim CMM, Salomon T, Crispim MAE, Oikawa MK, Grebe E, da Costa AG, Fraiji NA, Carvalho MDPSS, Whittaker C, Alexander N, Faria NR, Dye C, Nascimento VH, Busch MP, Sabino ECet al., 2022, Reinfection by the SARS-CoV-2 Gamma variant in blood donors in Manaus, Brazil, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334

BackgroundThe 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 Gamma during the second wave in Manaus and the protection conferred by previous infection, we identified anti-SARS-CoV-2 antibody boosting in repeat blood donors as a mean to infer reinfection.MethodsWe tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibodies using two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. Donors were required to have three or more donations, being at least one during each epidemic wave. We propose a strict serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants.ResultsFrom 3655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. We found 13.6% (95% CI 7.0–24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3–34.2%) and 39.3% (95% CI 29.5–50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3–92.

Journal article

Li SL, Acosta AL, Hill SC, Brady OJ, de Almeida MAB, Cardoso JDC, Hamlet A, Mucci LF, de Deus JT, Iani FCM, Alexander NS, Wint GRW, Pybus OG, Kraemer MUG, Faria NR, Messina JPet al., 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, Vol: 16, ISSN: 1935-2727

BackgroundYellow fever (YF) is an arboviral disease which is endemic to Brazil due to a sylvatic transmission cycle maintained by infected mosquito vectors, non-human primate (NHP) hosts, and humans. Despite the existence of an effective vaccine, recent sporadic YF epidemics have underscored concerns about sylvatic vector surveillance, as very little is known about their spatial distribution. Here, we model and map the environmental suitability of YF’s main vectors in Brazil, Haemagogus spp. and Sabethes spp., and use human population and NHP data to identify locations prone to transmission and spillover risk.Methodology/Principal findingsWe compiled a comprehensive set of occurrence records on Hg. janthinomys, Hg. leucocelaenus, and Sabethes spp. from 1991–2019 using primary and secondary data sources. Linking these data with selected environmental and land-cover variables, we adopted a stacked regression ensemble modelling approach (elastic-net regularized GLM, extreme gradient boosted regression trees, and random forest) to predict the environmental suitability of these species across Brazil at a 1 km x 1 km resolution. We show that while suitability for each species varies spatially, high suitability for all species was predicted in the Southeastern region where recent outbreaks have occurred. By integrating data on NHP host reservoirs and human populations, our risk maps further highlight municipalities within the region that are prone to transmission and spillover.Conclusions/SignificanceOur maps of sylvatic vector suitability can help elucidate potential locations of sylvatic reservoirs and be used as a tool to help mitigate risk of future YF outbreaks and assist in vector surveillance. Furthermore, at-risk regions identified from our work could help disease control and elucidate gaps in vaccination coverage and NHP host surveillance.

Journal article

Mee P, Alexander N, Mayaud P, González FDJC, Abbott S, Santos AADS, Acosta AL, Parag KV, Pereira RHM, Prete CA, Sabino EC, Faria NR, LSHTM Centre for Mathematical Modelling of Infectious Disease COVID-19 working group, Brady OJet al., 2022, 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, Vol: 5, Pages: None-None, ISSN: 2667-193X

BACKGROUND: 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. METHODS: 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. FINDINGS: 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:8.9,13.2] 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. INTERPRETATION: This study demonstrates that platforms that monitor, standardise and analyse the epidemiological data at a local level can give useful real-time insights into outbreak dynamics that can be used to better adapt responses to the current and future pandemics. FUNDING: This project was supported by a Medical Research Council UK (MRC-UK) -São Paulo Research Foundation (FAPESP) CADDE partnership award (MR/S0195/1 and FAPESP 18/1438

Journal article

McCrone JT, Hill V, Bajaj S, Pena RE, Lambert BC, Inward R, Bhatt S, Volz E, Ruis C, Dellicour S, Baele G, Zarebski AE, Sadilek A, Wu N, Schneider A, Ji X, Raghwani J, Jackson B, Colquhoun R, O'Toole Á, Peacock TP, Twohig K, Thelwall S, Dabrera G, Myers R, COVID-19 genomics UK COG-UK consortium, Faria NR, Huber C, Bogoch II, Khan K, du Plessis L, Barrett JC, Aanensen DM, Barclay WS, Chand M, Connor T, Loman NJ, Suchard MA, Pybus OG, Rambaut A, Kraemer MUGet al., 2021, Context-specific emergence and growth of the SARS-CoV-2 Delta variant., medRxiv

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases 1-3 . The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions 4,5 . Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

Journal article

McCrone JT, Hill V, Bajaj S, Pena RE, Lambert BC, Inward R, Bhatt S, Volz E, Ruis C, Dellicour S, Baele G, Zarebski AE, Sadilek A, Wu N, Schneider A, Ji X, Raghwani J, Jackson B, Colquhoun R, O'Toole Á, Peacock TP, Twohig K, Thelwall S, Dabrera G, Myers R, COVID-19 genomics UK COG-UK consortium, Faria NR, Huber C, Bogoch II, Khan K, du Plessis L, Barrett JC, Aanensen DM, Barclay WS, Chand M, Connor T, Loman NJ, Suchard MA, Pybus OG, Rambaut A, Kraemer MUGet al., 2021, Context-specific emergence and growth of the SARS-CoV-2 Delta variant., Res Sq

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta’s invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

Journal article

Scott L, Hsiao N-Y, Moyo S, Singh L, Tegally H, Dor G, Maes P, Pybus OG, Kraemer MUG, Semenova E, Bhatt S, Flaxman S, Faria NR, de Oliveira Tet al., 2021, Track Omicron's spread with molecular data, Science, Vol: 374, Pages: 1454-1455, ISSN: 0036-8075

Journal article

Brito AF, Semenova E, Dudas G, Hassler GW, Kalinich CC, Kraemer MUG, Ho J, Tegally H, Githinji G, Agoti CN, Matkin LE, Whittaker C, Danish Covid-19 Genome Consortium, COVID-19 Impact Project, Network for Genomic Surveillance in South Africa NGS-SA, GISAID core curation team, Howden BP, Sintchenko V, Zuckerman NS, Mor O, Blankenship HM, de Oliveira T, Lin RTP, Siqueira MM, Resende PC, Vasconcelos ATR, Spilki FR, Aguiar RS, Alexiev I, Ivanov IN, Philipova I, Carrington CVF, Sahadeo NSD, Gurry C, Maurer-Stroh S, Naidoo D, von Eije KJ, Perkins MD, van Kerkhove M, Hill SC, Sabino EC, Pybus OG, Dye C, Bhatt S, Flaxman S, Suchard MA, Grubaugh ND, Baele G, Faria NRet al., 2021, Global disparities in SARS-CoV-2 genomic surveillance.

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.

Working paper

Nicolete VC, Rodrigues PT, Johansen IC, Corder RM, Tonini J, Cardoso MA, de Jesus JG, Claro IM, Faria NR, Sabino EC, Castro MC, Ferreira MUet al., 2021, Interacting Epidemics in Amazonian Brazil: Prior Dengue Infection Associated With Increased Coronavirus Disease 2019 (COVID-19) Risk in a Population-Based Cohort Study, CLINICAL INFECTIOUS DISEASES, Vol: 73, Pages: 2045-2054, ISSN: 1058-4838

Journal article

de Souza WM, Muraro SP, Souza GF, Amorim MR, Sesti-Costa R, Mofatto LS, Forato J, Barbosa PP, Toledo-Teixeira DA, Bispo-dos-Santos K, Parise PL, Brunetti NS, Moreira JCO, Costa VA, Cardozo DM, Moretti ML, Barros-Mazon S, Marchesi GF, Ambrosio C, Spilki FR, Almeida VC, Vieira AS, Zambon L, Farias AS, Addas-Carvalho M, Benites BD, Marques RE, Sabino EC, Von Zuben AB, Weaver SC, Faria NR, Granja F, Angerami RN, Proenca-Modena JLet al., 2021, Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccines, VIRUSES-BASEL, Vol: 13

Journal article

de Souza WM, Fumagalli MJ, Carrera JP, de Araujo J, Cardoso JF, de Carvalho C, Durigon EL, Queiroz LH, Faria NR, Murcia PR, Figueiredo LTMet al., 2021, Paramyxoviruses from neotropical bats suggest a novel genus and nephrotropism, INFECTION GENETICS AND EVOLUTION, Vol: 95, ISSN: 1567-1348

Journal article

Brizzi A, Whittaker C, Servo LMS, Hawryluk I, Prete Jr CA, de Souza WM, Aguiar RS, Araujo LJT, Bastos LS, Blenkinsop A, Buss LF, Candido D, Castro MC, Costa SF, Croda J, de Souza Santos A, Dye C, Flaxman S, Fonseca PLC, Geddes VEV, Gutierrez B, Lemey P, Levin AS, Mellan T, Bonfim DM, Miscouridou X, Mishra S, Monod M, Moreira FRR, Nelson B, Pereira RHM, Ranzani O, Schnekenberg RP, Semenova E, Sonnabend R, Souza RP, Xi X, Sabino EC, Faria NR, Bhatt S, Ratmann Oet al., 2021, Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals

The SARS‐CoV‐2 Gamma variant spread rapidly across Brazil, causing substantial infection and death wa ves. We use individual‐level patient records following hospitalisation with suspected or confirmed COVID‐19 to document the extensive shocks in hospital fatality rates that followed Gamma’s spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time pe riods. We show that extensive fluctuations in COVID‐19 in‐hospital fatality rates also existed prior to Gamma’s detection, and were largely transient after Gamma’s detection, subsiding with hospital d emand. Using a Bayesian fatality rate model, we find that the geo‐graphic and temporal fluctuations in Brazil’s COVID‐19 in‐hospital fatality rates are primarily associated with geo‐graphic inequities and shortages in healthcare c apacity. We project that approximately half of Brazil’s COVID‐19 deaths in hospitals 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 trans‐missible and deadly pathogens such as SARS‐CoV‐2, especially in low‐ and middle‐income countries.

Report

Lima STSD, Souza WMD, Cavalcante JW, da Silva Candido D, Fumagalli MJ, Carrera J-P, Simões Mello LM, de Carvalho Araújo FM, Cavalcante Ramalho IL, de Almeida Barreto FK, de Melo Braga DN, Simião AR, Miranda da Silva MJ, Oliveira RDMAB, Lima CPS, Sousa Lins CD, Barata RR, Melo MNP, de Souza MPC, Franco LM, Távora FRF, Queiroz Lemos DR, Alencar CHMD, Jesus RD, Souza Fonseca VD, Dutra LH, Abreu ALD, Araújo ELL, Ribas Freitas AR, Gonçalves Vianez Júnior JLDS, Pybus OG, Moraes Figueiredo LT, Faria NR, Teixeira Nunes MR, Góes Cavalcanti LPD, Miyajima Fet al., 2021, Fatal outcome of chikungunya virus infection in Brazil., Clinical Infectious Diseases, Vol: 73, Pages: e2436-e2443, ISSN: 1058-4838

BACKGROUND: Chikungunya virus (CHIKV) emerged in the Americas in 2013 and has caused ~2.1 million cases and over 600 deaths. A retrospective investigation was undertaken to describe clinical, epidemiological and virus genomic features associated with deaths caused by CHIKV in Ceará state, northeast Brazil. METHODS: 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). Clinical, epidemiological and death reports were obtained for patients with confirmed CHIKV infection. Logistic regression analysis was undertaken to identify independent factors associated with risk of death during CHIKV infection. Phylogenetic analysis was conducted using whole genomes from a subset of cases. RESULTS: 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 were 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 circulation of two CHIKV-East Central South African (ECSA) lineages in Ceará and revealed no unique virus genomic mutation associated with fatal outcome. CONCLUSION: The investigation of the largest cross-sectional cohort of CHIKV-deaths to date reveals that CHIKV-ECSA strains can cause death in individuals from both risk and non-risk groups, including young adults.

Journal article

Whittaker C, Ratmann O, Dye C, Sabino EC, Faria NRet al., 2021, Altered demographic profile of hospitalizations during the second COVID-19 wave in Amazonas, Brazil, The Lancet Regional Health - Americas, Vol: 2, ISSN: 2667-193X

Journal article

Souza WM, Amorim MR, Sesti-Costa R, Coimbra LD, Brunetti NS, Toledo-Teixeira DA, de Souza GF, Muraro SP, Parise PL, Barbosa PP, Bispo-dos-Santos K, Mofatto LS, Simeoni CL, Claro IM, Duarte ASS, Coletti TM, Zangirolami AB, Costa-Lima C, Gomes ABSP, Buscaratti LI, Sales FC, Costa VA, Franco LAM, Candido DS, Pybus OG, de Jesus JG, Silva CAM, Ramundo MS, Ferreira GM, Pinho MC, Souza LM, Rocha EC, Andrade PS, Crispim MAE, Maktura GC, Manuli ER, Santos MNN, Camilo CC, Angerami RN, Moretti ML, Spilki FR, Arns CW, Addas-Carvalho M, Benites BD, Vinolo MAR, Mori MAS, Gaburo N, Dye C, Marques-Souza H, Marques RE, Farias AS, Diamond MS, Faria NR, Sabino EC, Granja F, Proença-Módena JLet al., 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, The Lancet Microbe, Vol: 2, Pages: e527-e535, ISSN: 2666-5247

BackgroundMutations 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.MethodsWe did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17–38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134–230 days after the second dose). Antibody neutralisation of P.1/28, P.1/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT50, defined as the reciprocal value of the sample dilution that showed 50% protection against cytopathic effects).FindingsIn terms of VNT50, plasma from individuals previously infected with SARS-CoV-2 had an 8·6 times lower neutralising capacity against the P.1 isolates (median VNT50 30 [IQR <20–45] for P.1/28

Journal article

Claro IM, Ramundo MS, Coletti TM, da Silva CAM, Valenca IN, Candido DS, Sales FCS, Manuli ER, de Jesus JG, de Paula A, Felix AC, Andrade PDS, Pinho MC, Souza WM, Amorim MR, Proenca-Modena JL, Kallas EG, Levi JE, Faria NR, Sabino EC, Loman NJ, Quick Jet al., 2021, Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing, Wellcome Open Research, Vol: 6, Pages: 241-241

<ns3:p>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.</ns3:p><ns3:p> 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.</ns3:p><ns3:p> This work demonstrates that SMART-9N and Rapid SMART-9N are sensitive, low input, and long-read compatible alternatives for RNA virus detection and

Journal article

O'Toole Á, Hill V, Pybus OG, Watts A, Bogoch II, Khan K, Messina JP, Tegally H, Lessells RR, Giandhari J, Pillay S, Tumedi KA, Nyepetsi G, Kebabonye M, Matsheka M, Mine M, Tokajian S, Hassan H, Salloum T, Merhi G, Koweyes J, Geoghegan JL, de Ligt J, Ren X, Storey M, Freed NE, Pattabiraman C, Prasad P, Desai AS, Vasanthapuram R, Schulz TF, Steinbrück L, Stadler T, Parisi A, Bianco A, García de Viedma D, Buenestado-Serrano S, Borges V, Isidro J, Duarte S, Gomes JP, Zuckerman NS, Mandelboim M, Mor O, Seemann T, Arnott A, Draper J, Gall M, Rawlinson W, Deveson I, Schlebusch S, McMahon J, Leong L, Lim CK, Chironna M, Loconsole D, Bal A, Josset L, Holmes E, St George K, Lasek-Nesselquist E, Sikkema RS, Oude Munnink B, Koopmans M, Brytting M, Sudha rani V, Pavani S, Smura T, Heim A, Kurkela S, Umair M, Salman M, Bartolini B, Rueca M, Drosten C, Wolff T, Silander O, Eggink D, Reusken C, Vennema H, Park A, Carrington C, Sahadeo N, Carr M, Gonzalez G, de Oliveira T, Faria N, Rambaut A, Kraemer MUGet al., 2021, Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y-V2 with grinch, Wellcome Open Research, Vol: 6, Pages: 121-121

<ns3:p>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.</ns3:p>

Journal article

Gutierrez B, Marquez S, Prado-Vivar B, Becerra-Wong M, Jose Guadalupe J, Da Silva Candido D, Carlos Fernandez-Cadena J, Morey-Leon G, Armas-Gonzalez R, Madeleiny Andrade-Molina D, Bruno A, De Mora D, Olmedo M, Portugal D, Gonzalez M, Orlando A, Drexler JF, Moreira-Soto A, Sander A-L, Bruenink S, Kuhne A, Patino L, Carrazco-Montalvo A, Mestanza O, Zurita J, Sevillano G, Du Plessis L, McCrone JT, Coloma J, Trueba G, Barragan V, Rojas-Silva P, Grunauer M, Kraemer MUG, Faria NR, Escalera-Zamudio M, Pybus OG, Cardenas Pet al., 2021, Genomic epidemiology of SARS-CoV-2 transmission lineages in Ecuador, VIRUS EVOLUTION, Vol: 7

Journal article

Kraemer MUG, Hill V, Ruis C, Dellicour S, Bajaj S, McCrone JT, Baele G, Parag KV, Battle AL, Gutierrez B, Jackson B, Colquhoun R, O'Toole Á, Klein B, Vespignani A, COVID-19 Genomics UK CoG-UK consortium, Volz E, Faria NR, Aanensen D, Loman NJ, du Plessis L, Cauchemez S, Rambaut A, Scarpino SV, Pybus OGet al., 2021, Spatiotemporal invasion dynamics of SARS-CoV-2 lineage B.1.1.7 emergence, Science, Vol: 373, Pages: 889-895, ISSN: 0036-8075

Understanding the causes and consequences of the emergence of SARS-CoV-2 variants of concern is crucial to pandemic control yet difficult to achieve, as they arise in the context of variable human behavior and immunity. We investigate the spatial invasion dynamics of lineage B.1.1.7 by jointly analyzing UK human mobility, virus genomes, and community-based PCR data. We identify a multi-stage spatial invasion process in which early B.1.1.7 growth rates were associated with mobility and asymmetric lineage export from a dominant source location, enhancing the effects of B.1.1.7's increased intrinsic transmissibility. We further explore how B.1.1.7 spread was shaped by non-pharmaceutical interventions and spatial variation in previous attack rates. Our findings show that careful accounting of the behavioral and epidemiological context within which variants of concern emerge is necessary to interpret correctly their observed relative growth rates.

Journal article

Dellicour S, Gill MS, Faria NR, Rambaut A, Pybus OG, Suchard MA, Lemey Pet al., 2021, Relax, Keep Walking - A Practical Guide to Continuous Phylogeographic Inference with BEAST, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 38, Pages: 3486-3493, ISSN: 0737-4038

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Iani FCM, Giovanetti M, Fonseca V, Souza WM, Adelino TER, Xavier J, Jesus JG, Pereira MA, Silva MVF, Costa AVB, Silva EC, Mendes MCO, Filippis AMB, Albuquerque CFC, Abreu AL, Oliveira MAA, Alcantara LCJ, Faria NRet al., 2021, Epidemiology and evolution of Zika virus in Minas Gerais, Southeast Brazil, INFECTION GENETICS AND EVOLUTION, Vol: 91, ISSN: 1567-1348

Journal article

Whittaker C, Watson OJ, Alvarez-Moreno C, Angkasekwinai N, Boonyasiri A, Triana LC, Chanda D, Charoenpong L, Chayakulkeeree M, Cooke GS, Croda J, Cucunubá ZM, Djaafara BA, Estofolete CF, Grillet ME, Faria NR, Costa SF, Forero-Peña DA, Gibb DM, Gordon AC, Hamers RL, Hamlet A, Irawany V, Jitmuang A, Keurueangkul N, Kimani TN, Lampo M, Levin AS, Lopardo G, Mustafa R, Nayagam S, Ngamprasertchai T, Hannah Njeri NI, Nogueira ML, Ortiz-Prado E, Perroud MW, Phillips AN, Promsin P, Qavi A, Rodger AJ, Sabino EC, Sangkaew S, Sari D, Sirijatuphat R, Sposito AC, Srisangthong P, Thompson HA, Udwadia Z, Valderrama-Beltrán S, Winskill P, Ghani AC, Walker PGT, Hallett TBet al., 2021, Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The unprecedented 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.</jats:p></jats:sec><jats:sec><jats:title>Methods and Findings</jats:title><jats:p>We develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>There is a global asymmetry in who is likely to benefit from advances in the treatment of

Journal article

Mendes-Correa MC, Ghilardi F, Salomão MC, Villas-Boas LS, Vicente de Paula A, Tozetto-Mendoza TR, Freire W, Sales FC, Romano CM, Claro IM, de Souza LM, Ramos JF, Paiao HGO, Szor RS, Kallas EG, Sabino EC, Witkin SS, Faria NRet al., 2021, SARS-CoV-2 shedding, infectivity and evolution in an immunocompromised adult patient

<jats:title>Abstract</jats:title><jats:p>This report describes a persistent SARS-CoV-2 infection of at least 218 days in a male, in his 40’s who had undergone a prior autologous hematopoietic stem cell transplant due to a diffuse large B-cell lymphoma. He did not manifest a humoral immune response to the virus. Whole-genome sequencing and viral cultures confirmed a continual infection with a replication-positive virus that had undergone genetic variation for at least 196 days following symptom onset.</jats:p>

Journal article

Moreira FRR, Bonfim DM, Zauli DAG, Silva JP, Lima AB, Malta FSV, Ferreira ACS, Pardini VC, Magalhaes WCS, Queiroz DC, Souza RM, Geddes VEV, Costa WC, Moreira RG, Faria NR, Voloch CM, Souza RP, Aguiar RSet al., 2021, Epidemic spread of SARS-CoV-2 lineage B.1.1.7 in Brazil, Viruses-Basel, Vol: 13, Pages: 1-4, ISSN: 1999-4915

Journal article

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