RESUMEN
Almost simultaneously, several studies reported the emergence of novel SARS-CoV-2 lineages characterized by their phylogenetic and genetic distinction (1), (2), (3), (4). .
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COVID-19 , Pandemias , SARS-CoV-2/genética , Brasil/epidemiología , COVID-19/epidemiología , COVID-19/virología , HumanosRESUMEN
Brazil currently ranks second in absolute deaths by COVID-19, even though most of its population has completed the vaccination protocol. With the introduction of Omicron in late 2021, the number of COVID-19 cases soared once again in the country. We investigated in this work how lineages BA.1 and BA.2 entered and spread in the country by sequencing 2173 new SARS-CoV-2 genomes collected between October 2021 and April 2022 and analyzing them in addition to more than 18,000 publicly available sequences with phylodynamic methods. We registered that Omicron was present in Brazil as early as 16 November 2021 and by January 2022 was already more than 99% of samples. More importantly, we detected that Omicron has been mostly imported through the state of São Paulo, which in turn dispersed the lineages to other states and regions of Brazil. This knowledge can be used to implement more efficient non-pharmaceutical interventions against the introduction of new SARS-CoV variants focused on surveillance of airports and ground transportation.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Brasil/epidemiología , Transportes , VacunaciónRESUMEN
During the first semester of 2021, all of Brazil has suffered an intense wave of COVID-19 associated with the Gamma variant. In July, the first cases of Delta variant were detected in the state of Rio de Janeiro. In this work, we have employed phylodynamic methods to analyse more than 1â600 genomic sequences of Delta variant collected until September in Rio de Janeiro to reconstruct how this variant has surpassed Gamma and dispersed throughout the state. After the introduction of Delta, it has initially spread mostly in the homonymous city of Rio de Janeiro, the most populous of the state. In a second stage, dispersal occurred to mid- and long-range cities, which acted as new close-range hubs for spread. We observed that the substitution of Gamma by Delta was possibly caused by its higher viral load, a proxy for transmissibility. This variant turnover prompted a new surge in cases, but with lower lethality than was observed during the peak caused by Gamma. We reason that high vaccination rates in the state of Rio de Janeiro were possibly what prevented a higher number of deaths.
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COVID-19 , SARS-CoV-2 , Brasil/epidemiología , COVID-19/epidemiología , Humanos , SARS-CoV-2/genéticaRESUMEN
In this study, we report the first case of intra-host SARS-CoV-2 recombination during a coinfection by the variants of concern (VOC) AY.33 (Delta) and P.1 (Gamma) supported by sequencing reads harboring a mosaic of lineage-defining mutations. By using next-generation sequencing reads intersecting regions that simultaneously overlap lineage-defining mutations from Gamma and Delta, we were able to identify a total of six recombinant regions across the SARS-CoV-2 genome within a sample. Four of them mapped in the spike gene and two in the nucleocapsid gene. We detected mosaic reads harboring a combination of lineage-defining mutations from each VOC. To our knowledge, this is the first report of intra-host RNA-RNA recombination between two lineages of SARS-CoV-2, which can represent a threat to public health management during the COVID-19 pandemic due to the possibility of the emergence of viruses with recombinant phenotypes.
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COVID-19 , Coinfección , Humanos , Pandemias , Filogenia , SARS-CoV-2/genéticaRESUMEN
The sharp increase of COVID-19 cases in late 2020 has made Brazil the new epicenter of the ongoing SARS-CoV-2 pandemic. The novel viral lineages P.1 (Variant of Concern Gamma) and P.2, respectively identified in the Brazilian states of Amazonas and Rio de Janeiro, have been associated with potentially higher transmission rates and antibody neutralization escape. In this study, we performed the whole-genome sequencing of 185 samples isolated from three out of the five Brazilian regions, including Amazonas (North region), Rio Grande do Norte, Paraíba and Bahia (Northeast region), and Rio de Janeiro (Southeast region) in order to monitor the spread of SARS-CoV-2 lineages in Brazil in the first months of 2021. Here, we showed a widespread dispersal of P.1 and P.2 across Brazilian regions and, except for Amazonas, P.2 was the predominant lineage identified in the sampled states. We estimated the origin of P.2 lineage to have happened in February, 2020 and identified that it has differentiated into new clades. Interstate transmission of P.2 was detected since March, but reached its peak in December, 2020 and January, 2021. Transmission of P.1 was also high in December and its origin was inferred to have happened in August 2020. We also confirmed the presence of lineage P.7, recently described in the southernmost region of Brazil, to have spread across the Northeastern states. P.1, P.2 and P.7 are descended from the ancient B.1.1.28 strain, which co-dominated the first phase of the pandemic in Brazil with the B.1.1.33 strain. We also identified the occurrence of a new lineage descending from B.1.1.33 that convergently carries the E484K mutation, N.9. Indeed, the recurrent report of many novel SARS-CoV-2 genetic variants in Brazil could be due to the absence of effective control measures resulting in high SARS-CoV2 transmission rates. Altogether, our findings provided a landscape of the critical state of SARS-CoV-2 across Brazil and confirm the need to sustain continuous sequencing of the SARS-CoV-2 isolates worldwide in order to identify novel variants of interest and monitor for vaccine effectiveness.
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COVID-19/epidemiología , COVID-19/virología , Genoma Viral , Genómica/métodos , SARS-CoV-2 , Brasil/epidemiología , COVID-19/transmisión , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Filogenia , SARS-CoV-2/clasificación , SARS-CoV-2/genéticaRESUMEN
Long-term infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a challenge to virus dispersion and the control of coronavirus disease 2019 (COVID-19) pandemic. The reason why some people have prolonged infection and how the virus persists for so long are still not fully understood. Recent studies suggested that the accumulation of intra-host single nucleotide variants (iSNVs) over the course of the infection might play an important role in persistence as well as emergence of mutations of concern. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during prolonged infection. Thirty-three patients who remained reverse transcription polymerase chain reaction (RT-PCR) positive in the nasopharynx for on average 18 days from the symptoms onset were included in this study. Whole-genome sequences were obtained for each patient at two different time points. Phylogenetic, populational, and computational analyses of viral sequences were consistent with prolonged infection without evidence of coinfection in our cohort. We observed an elevated within-host genomic diversity at the second time point samples positively correlated with cycle threshold (Ct) values (lower viral load). Direct transmission was also confirmed in a small cluster of healthcare professionals that shared the same workplace by the presence of common iSNVs. A differential accumulation of missense variants between the time points was detected targeting crucial structural and non-structural proteins such as Spike and helicase. Interestingly, longitudinal acquisition of iSNVs in Spike protein coincided in many cases with SARS-CoV-2 reactive and predicted T cell epitopes. We observed a distinguishing pattern of mutations over the course of the infection mainly driven by increasing AâU and decreasing GâA signatures. GâA mutations may be associated with RNA-editing enzyme activities; therefore, the mutational profiles observed in our analysis were suggestive of innate immune mechanisms of the host cell defense. Therefore, we unveiled a dynamic and complex landscape of host and pathogen interaction during prolonged infection of SARS-CoV-2, suggesting that the host's innate immunity shapes the increase of intra-host diversity. Our findings may also shed light on possible mechanisms underlying the emergence and spread of new variants resistant to the host immune response as recently observed in COVID-19 pandemic.
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In the present study, we provide a retrospective genomic epidemiology analysis of the SARS-CoV-2 pandemic in the state of Rio de Janeiro, Brazil. We gathered publicly available data from GISAID and sequenced 1927 new genomes sampled periodically from March 2021 to June 2021 from 91 out of the 92 cities of the state. Our results showed that the pandemic was characterized by three different phases driven by a successive replacement of lineages. Interestingly, we noticed that viral supercarriers accounted for the overwhelming majority of the circulating virus (>90%) among symptomatic individuals in the state. Moreover, SARS-CoV-2 genomic surveillance also revealed the emergence and spread of two new variants (P.5 and P.1.2), firstly reported in this study. Our findings provided important lessons learned from the different epidemiological aspects of the SARS-CoV-2 dynamic in Rio de Janeiro. Altogether, this might have a strong potential to shape future decisions aiming to improve public health management and understanding mechanisms underlying virus dispersion.