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1.
Biologicals ; 2022.
Article in English | ScienceDirect | ID: covidwho-2007466

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, is the causative agent of the coronavirus disease 2019 (COVID-19). Since its first notification in São Paulo state (SP) on 26th February 2020, more than 22,300,000 cases and 619,000 deaths were reported in Brazil. In early pandemic, SARS-CoV-2 spread locally, however, over time, this virus was disseminated to other regions of the country. Herein, we performed genomic sequencing and phylogenetic analysis of SARS-CoV-2 using 20 clinical samples of COVID-19 confirmed cases from 9 cities of Minas Gerais state (MG), in order to evaluate the molecular properties of circulating viral strains in this locality from March to May 2020. Our analyses demonstrated the circulation of B.1 lineage isolates in the investigated locations and nucleotide substitutions were observed into the genomic regions related to important viral structures. Additionally, sequences generated in this study clustered with isolates from SP, suggesting a dissemination route between these two states. Alternatively, monophyletic groups of sequences from MG and other states or country were observed, indicating independent events of virus introduction. These results reinforce the need of genomic surveillance for understand the ongoing spread of emerging viral pathogens.

3.
Cell Host Microbe ; 30(8): 1112-1123.e3, 2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-1894865

ABSTRACT

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


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Genome, Viral , Humans , Phylogeny , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics
4.
Nat Med ; 28(7): 1476-1485, 2022 07.
Article in English | MEDLINE | ID: covidwho-1830084

ABSTRACT

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


Subject(s)
COVID-19 , Aged , Aged, 80 and over , Bayes Theorem , Brazil/epidemiology , COVID-19/epidemiology , Hospitals , Humans , SARS-CoV-2
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308600

ABSTRACT

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.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292948

ABSTRACT

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

7.
Virus Evol ; 7(2): veab051, 2021.
Article in English | MEDLINE | ID: covidwho-1412522

ABSTRACT

Characterisation of severe acute respiratory syndrome coronavirus-2 (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 coronavirus-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, with differential degrees of persistence and national dissemination.

8.
Lancet Microbe ; 2(10): e527-e535, 2021 10.
Article in English | MEDLINE | ID: covidwho-1307293

ABSTRACT

BACKGROUND: 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. METHODS: 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. 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). FINDINGS: In 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 and 30 [<20-40] for P.1/30) than against the lineage B isolate (260 [160-400]), with a binominal model showing significant reductions in lineage P.1 isolates compared with the lineage B isolate (p≤0·0001). Efficient neutralisation of P.1 isolates was not seen with plasma samples collected from individuals vaccinated with a first dose of CoronaVac 20-23 days earlier (VNT50s below the limit of detection [<20] for most plasma samples), a second dose 17-38 days earlier (median VNT50 24 [IQR <20-25] for P.1/28 and 28 [<20-25] for P.1/30), or a second dose 134-260 days earlier (all VNT50s below limit of detection). Median VNT50s against the lineage B isolate were 20 (IQR 20-30) after a first dose of CoronaVac 20-23 days earlier, 75 (<20-263) after a second dose 17-38 days earlier, and 20 (<20-30) after a second dose 134-260 days earlier. In plasma collected 17-38 days after a second dose of CoronaVac, neutralising capacity against both P.1 isolates was significantly decreased (p=0·0051 for P.1/28 and p=0·0336 for P.1/30) compared with that against the lineage B isolate. All data were corroborated by results obtained through plaque reduction neutralisation tests. INTERPRETATION: 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. FUNDING: São Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Brazil/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2/genetics , United States , Vaccination
9.
Rev Inst Med Trop Sao Paulo ; 63: e36, 2021.
Article in English | MEDLINE | ID: covidwho-1288733

ABSTRACT

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.


Subject(s)
COVID-19 , Reinfection , SARS-CoV-2 , Brazil/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Humans , Reinfection/virology , SARS-CoV-2/isolation & purification
10.
Rev Inst Med Trop Sao Paulo ; 63: e36, 2021.
Article in English | MEDLINE | ID: covidwho-1206220

ABSTRACT

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.


Subject(s)
COVID-19 , Reinfection , SARS-CoV-2 , Brazil/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Humans , Reinfection/virology , SARS-CoV-2/isolation & purification
11.
Science ; 372(6544): 815-821, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1186201

ABSTRACT

Cases of severe acute respiratory syndrome coronavirus 2 (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 (angiotensin-converting enzyme 2) 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- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 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.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/virology , SARS-CoV-2/classification , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/metabolism , Brazil/epidemiology , Epidemiological Monitoring , Genome, Viral , Genomics , Humans , Models, Theoretical , Molecular Epidemiology , Mutation , Protein Binding , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/metabolism , Viral Load
13.
Sci Data ; 8(1): 73, 2021 03 04.
Article in English | MEDLINE | ID: covidwho-1117653

ABSTRACT

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


Subject(s)
COVID-19/prevention & control , Communicable Disease Control/methods , Brazil , COVID-19/transmission , Cities , Humans , Pandemics
14.
Emerg Infect Dis ; 27(3): 970-972, 2021 03.
Article in English | MEDLINE | ID: covidwho-1048946

ABSTRACT

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.


Subject(s)
COVID-19 , Phylogeny , SARS-CoV-2/isolation & purification , Travel , Adult , Brazil , COVID-19/epidemiology , COVID-19/virology , Female , Genome, Viral , Humans , Male , Young Adult
15.
Nat Hum Behav ; 4(8): 856-865, 2020 08.
Article in English | MEDLINE | ID: covidwho-690410

ABSTRACT

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.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections , Disease Transmission, Infectious , Influenza, Human , Pandemics , Pneumonia, Viral , Adult , Aged , Brazil/epidemiology , COVID-19 , COVID-19 Testing , Child , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/statistics & numerical data , Coinfection/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Disease Transmission, Infectious/prevention & control , Disease Transmission, Infectious/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Infant , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Influenza, Human/virology , Male , Mortality , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , SARS-CoV-2 , Socioeconomic Factors
16.
Science ; 369(6508): 1255-1260, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-675945

ABSTRACT

Brazil currently has one of the fastest-growing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics in the world. 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.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Basic Reproduction Number , Bayes Theorem , Betacoronavirus/classification , Brazil/epidemiology , COVID-19 , COVID-19 Testing , Cities/epidemiology , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Europe , Evolution, Molecular , Genome, Viral , Humans , Models, Genetic , Models, Statistical , Pandemics/prevention & control , Phylogeny , Phylogeography , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , SARS-CoV-2 , Spatio-Temporal Analysis , Travel , Urban Population
18.
Rev Inst Med Trop Sao Paulo ; 62: e30, 2020.
Article in English | MEDLINE | ID: covidwho-246727

ABSTRACT

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.


Subject(s)
Betacoronavirus/genetics , Communicable Diseases, Imported/transmission , Coronavirus Infections/transmission , Pandemics , Pneumonia, Viral/transmission , Aged , Brazil/epidemiology , COVID-19 , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/virology , Coronavirus Infections/epidemiology , Humans , Middle Aged , Phylogeny , Pneumonia, Viral/epidemiology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
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