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1.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21266109

Résumé

The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma during late 2020 and early 2021 in Brazilian settings with high seroprevalence raised some concern about the potential role of reinfections in driving the epidemic. Very few cases of reinfection associated with the VOC Gamma, however, have been reported. Here we describe 25 cases of SARS-CoV-2 reinfection confirmed by real-time RT-PCR twice within months apart in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected between March and December 2020 with distinct viral lineages, including B.1.1, B.1.1.28, B.1.1.33, B.1.195 and P.2, and then reinfected with the VOC Gamma between 3 to 12 months after primo-infection. The overall mean cycle threshold (Ct) value of the first (25.7) and second (24.5) episodes were roughly similar for the whole group and 14 individuals displayed mean Ct values < 25.0 at reinfection. Sera of 14 patients tested by plaque reduction neutralization test after reinfection displayed detectable neutralizing antibodies against Gamma and other SARS-CoV-2 variants (B.1.33, B.1.1.28 and Delta). All individuals have milder or no symptoms after reinfection and none required hospitalization. The present study demonstrates that the VOC Gamma was associated with reinfections during the second Brazilian epidemic wave in 2021 and raised concern about the potential infectiousness of reinfected subjects. Although individuals here analyzed failed to mount a long-term sterilizing immunity, they developed a high anti-Gamma neutralizing antibody response after reinfection that may provide some protection against severe disease.

2.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21266251

Résumé

The SARS-CoV-2 Variant of Concern (VOC) Delta was first detected in India in October 2020. The first imported cases of the Delta variant in Brazil were identified in April 2021 in the Southern region, followed by more cases in different country regions during the following months. By early September 2021, Delta was already the dominant variant in the Southeastern (87%), Southern (73%), and Northeastern (52%) Brazilian regions. This work aimed to understand the spatiotemporal dissemination dynamics of Delta in Brazil. To this end, we employed a combination of Maximum Likelihood (ML) and Bayesian methods to reconstruct the evolutionary relationship of 2,264 of VOC Delta complete genomes (482 from this study) recovered across 21 out of 27 Brazilian federal units. Our phylogeographic analyses identified three major transmission clusters of Delta in Brazil. The clade BR-I (n = 1,560) arose in Rio de Janeiro in late April 2021 and was the major cluster behind the dissemination of the VOC Delta in the Southeastern, Northeastern, Northern, and Central-Western regions. The clade BR-II (n = 207) arose in the Parana state in late April 2021 and aggregated the largest fraction of sampled genomes from the Southern region. Lastly, the clade BR-III emerged in the Sao Paulo state in early June 2021 and remained mostly restricted to this state. In the rapid turnover of viral variants characteristic of the SARS-CoV-2 pandemic, Brazilian regions seem to occupy different stages of an increasing prevalence of the VOC Delta in their epidemic profiles. This process demands continuous genomic and epidemiological surveillance toward identifying and mitigating new introductions, limiting their dissemination, and preventing the establishment of more significant outbreaks in a population already heavily affected by the COVID-19 pandemic.

3.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21265116

Résumé

The COVID-19 epidemic in Brazil experienced two major country-wide lineage replacements, the first driven by the lineage P.2, formerly classified as variant of interest (VOI) Zeta in late 2020 and the second by the variant of concern (VOC) Gamma in early 2021. To better understand how these SARS-CoV-2 lineage turnovers occurred in Brazil, we analyzed 11,724 high-quality SARS-CoV-2 whole genomes of samples collected in different country regions between September 2020 and April 2021. Our findings indicate that the spatial dispersion of both variants in Brazil was driven by short and long-distance viral transmission. The lineage P.2 harboring Spike mutation E484K probably emerged around late July 2020 in the Rio de Janeiro (RJ) state, which contributed with most ([~]50%) inter-state viral disseminations, and only became locally established in most Brazilian states by October 2020. The VOC Gamma probably arose in November 2020 in the Amazonas (AM) state, which was responsible for 60-70% of the inter-state viral dissemination, and the earliest timing of community transmission of this VOC in many Brazilian states was already traced to December 2020. We estimate that variant Gamma was 1.56-3.06 more transmissible than variant P.2 co-circulating in RJ and that the median effective reproductive number (Re) of Gamma in RJ and SP states (Re = 1.59-1.91) was lower than in AM (Re = 3.55). In summary, although the epicenter of the lineage P.2 dissemination in Brazil was the heavily interconnected Southeastern region, it displayed a slower rate of spatial spread than the VOC Gamma originated in the more isolated Northern Brazilian region. Our findings also support that the VOC Gamma was more transmissible than lineage P.2, although the viral Re of the VOC varied according to the geographic context.

4.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21263755

Résumé

The SARS-CoV-2 has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by infection waves of viral lineages showing distinct fitness profiles. The simultaneous infection of a single individual by two distinct SARS-CoV-2 lineages provides a window of opportunity for viral recombination and the emergence of new lineages with differential phenotype. Several hundred SARS-CoV-2 lineages are currently well characterized but two main factors have precluded major coinfection/codetection analysis thus far: i) the low diversity of SARS-CoV-2 lineages during the first year of the pandemic which limited the identification of lineage defining mutations necessary to distinguish coinfecting viral lineages; and the ii) limited availability of raw sequencing data where abundance and distribution of intrasample/intrahost variability can be accessed. Here, we have put together a large sequencing dataset from Brazilian samples covering a period of 18 May 2020 to 30 April 2021 and probed it for unexpected patterns of high intrasample/intrahost variability. It enabled us to detect nine cases of SARS-CoV-2 coinfection with well characterized lineage-defining mutations. In addition, we matched these SARS-CoV-2 coinfections with spatio-temporal epidemiological data confirming their plausibility with the co-circulating lineages at the timeframe investigated. These coinfections represent around 0.61% of all samples investigated. Although our data suggests that coinfection with distinct SARS-CoV-2 lineages is a rare phenomenon, it is likely an underestimation and coinfection rates warrants further investigation. DATA SUMMARYThe raw fastq data of codetection cases are deposited on gisaid.org and correlated to gisaid codes: EPI_ISL_1068258, EPI_ISL_2491769, EPI_ISL_2491781, EPI_ISL_2645599, EPI_ISL_2661789, EPI_ISL_2661931, EPI_ISL_2677092, EPI_ISL_2777552, EPI_ISL_3869215. Supplementary data are available on https://doi.org/10.6084/m9.figshare.16570602.v1. The workflow code used in this study is publicly available on: https://github.com/dezordi/IAM_SARSCOV2.

5.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21263701

Résumé

All South American countries from the Southern cone (Argentina, Brazil, Chile, Paraguay and Uruguay) experienced severe COVID-19 epidemic waves during early 2021 driven by the expansion of variants Gamma and Lambda, however, there was an improvement in different epidemic indicators since June 2021. To investigate the impact of national vaccination programs and natural infection on viral transmission in those South American countries, we analyzed the coupling between population mobility and the viral effective reproduction number Rt. Our analyses reveal that population mobility was highly correlated with viral Rt from January to May 2021 in all countries analyzed; but a clear decoupling occurred since May-June 2021, when the rate of viral spread started to be lower than expected from the levels of social interactions. These findings support that populations from the South American Southern cone probably achieved the conditional herd immunity threshold to contain the spread of regional SARS-CoV-2 variants.

6.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21263453

Résumé

The Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated as Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly{Delta} 144 or{Delta} 141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we found no overrepresentation of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sub-lineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting new variants with higher infectivity are expected to increase.

7.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21261150

Résumé

Uruguay was able to control the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein we analyzed the country-wide genetic diversity of SARS-CoV-2 between November, 2020 and April, 2021. Our findings identified that the most prevalent viral variant during late 2020 was a B.1.1.28 sublineage carrying mutations Q675H+Q677H in the viral Spike, now designated as lineage P.6. This new lineage P.6 probably arose around November 2020, in Montevideo, Uruguays capital department and rapidly spread to other Uruguayan departments, with evidence of further local transmission clusters, also spread sporadically to the USA and Spain. The Q675H and Q677H mutations are in the proximity of the polybasic cleavage site at the S1/S2 boundary and also arose independently in many SARS-CoV-2 lineages circulating worldwide. Although the lineage P.6 was replaced by the Variant of Concern (VOC) P.1 as the predominant viral strain in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H+Q677H in VOCs should be of worldwide interest.

8.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21259760

Résumé

During the first nine months of the SARS-CoV-2 pandemic, Uruguay successfully kept it under control, even when our previous studies support a recurrent viral flux across the Uruguayan-Brazilian border that sourced several local outbreaks in Uruguay. However, towards the end of 2020, a remarkable exponential growth was observed and the TETRIS strategy was lost. Here, we aimed to understand the factors that fueled SARS-CoV-2 viral dynamics during the first epidemic wave in the country. We recovered 84 whole viral genomes from patients diagnosed between November, 2020 and February, 2021 in Rocha, a sentinel eastern Uruguayan department bordering Brazil. The lineage B.1.1.28 was the most prevalent in Rocha during November-December 2020, P.2 became the dominant one during January-February 2021, while the first P.1 sequences corresponds to February, 2021. The lineage replacement process agrees with that observed in several Brazilian states, including Rio Grande do Sul (RS). We observed a one to three month delay between the appearance of P.2 and P.1 in RS and their subsequent detection in Rocha. The phylogenetic analysis detected two B.1.1.28 and one P.2 main Uruguayan SARS-CoV-2 clades, introduced from the southern and southeastern Brazilian regions into Rocha between early November and mid December, 2020. One synonymous mutation distinguishes the sequences of the main B.1.1.28 clade in Rocha from those widely distributed in RS. The minor B.1.1.28 cluster, distinguished by several mutations, harbours non-synonymous changes in the Spike protein: Q675H and Q677H, so far not concurrently reported. The convergent appearance of S:Q677H in different viral lineages and its proximity to the S1/S2 cleavage site raise concerns about its functional relevance. The observed S:E484K-VOI P.2 partial replacement of previously circulating lineages in Rocha might have increased transmissibility as suggested by the significant decrease in Ct values. Our study emphasizes the impact of Brazilian SARS-CoV-2 epidemics in Uruguay and the need of reinforcing real-time genomic surveillance on specific Uruguayan border locations, as one of the key elements for achieving long-term COVID-19 epidemic control.

10.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21253946

Résumé

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the SARS-CoV-2 Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil is generating new viral lineages that might be more resistant to neutralization than parental variants of concern.

11.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-434969

Résumé

The SARS-CoV-2 epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. Two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved within lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North and Northeast regions.

12.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20249026

Résumé

BackgroundUruguay is one of the few countries in the Americas that successfully contained the COVID-19 epidemic during the first half of 2020. Nevertheless, the intensive human mobility across the dry border with Brazil is a major challenge for public health authorities. We aimed to investigate the origin of SARS-CoV-2 strains detected in Uruguayan localities bordering Brazil as well as to measure the viral flux across this [~]1,100 km uninterrupted dry frontier. MethodsUsing complete SARS-CoV-2 genomes from the Uruguayan-Brazilian bordering region and phylogeographic analyses, we inferred the virus dissemination frequency between Brazil and Uruguay and characterized local outbreak dynamics during the first months (May-July) of the pandemic. FindingsPhylogenetic analyses revealed multiple introductions of SARS-CoV-2 Brazilian lineages B.1.1.28 and B.1.1.33 into Uruguayan localities at the bordering region. The most probable sources of viral strains introduced to Uruguay were the Southeast Brazilian region and the state of Rio Grande do Sul. Some of the viral strains introduced in Uruguayan border localities between early May and mid-July were able to locally spread and originated the first outbreaks detected outside the metropolitan region. The viral lineages responsible for Uruguayan suburban outbreaks were defined by a set of between four and 11 mutations (synonymous and non-synonymous) respect to the ancestral B.1.1.28 and B.1.1.33 viruses that arose in Brazil, supporting the notion of a rapid genetic differentiation between SARS-CoV-2 subpopulations spreading in South America. InterpretationAlthough Uruguayan borders have remained essentially closed to non-Uruguayan citizens, the inevitable flow of people across the dry border with Brazil allowed the repeated entry of the virus into Uruguay and the subsequent emergence of local outbreaks in Uruguayan border localities. Implementation of coordinated bi-national surveillance systems are crucial to achieve an efficient control of the SARS-CoV-2 spread across this kind of highly permeable borderland regions around the world. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of coronavirus disease 19 (COVID-19), was first detected in South America on February 26, 2020, it has rapidly spread through the region, causing nearly 350,000 deaths by December, 2020. In contrast to most American countries, Uruguay avoided an early exponential growth of SARS-CoV-2 cases and during the first six months of the pandemic it registered the lowest incidence of SARS-CoV-2 cases and deaths among South American countries. The intensive cross-border human mobility through the [~]1,100 km uninterrupted dry frontier between Uruguay and Brazil, might poses a major challenge for long-term control of the epidemic in Uruguay. Previous genomic studies conducted in Uruguay have analyzed sequences mostly sampled at the capital city, Montevideo, and detected prevalent SARS-CoV-2 lineages different from those described in Brazil, thus finding no evidence of frequent viral exchanges between these countries. Added value of this studyHere we present the first genomic study of SARS-CoV-2 strains detected in different Uruguayan and Brazilian localities along the bordering region. The samples analyzed include 30% (n = 59) of all laboratory confirmed SARS-CoV-2 cases from Uruguayan departments at the Brazilian border between March and July, 2020, as well as 68 SARS-CoV-2 sequences from individuals diagnosed in the southernmost Brazilian state of Rio Grande do Sul between March and August, 2020. We demonstrate that SARS-CoV-2 viral lineages that widely spread in the Southeastern Brazilian region (B.1.1.28 and B.1.1.33) were also responsible for most viral infections in Rio Grande do Sul and neighboring Uruguayan localities. We further uncover that major outbreaks detected in Uruguayan localities bordering Brazil in May and June, 2020, were originated from two independent introduction events of the Brazilian SARS-CoV-2 lineage B.1.1.33, unlike previous outbreaks in the Uruguayan metropolitan region that were seeded by European SARS-CoV-2 lineages. Implications of all the available evidenceOur findings confirm that although Uruguayan borders have remained essentially closed to non-Uruguayan citizens, dissemination of SARS-CoV-2 across the Uruguayan-Brazilian frontier was not fully suppressed and had the potential to ignite local transmission chains in Uruguay. These findings also highlight the relevance of implementing bi-national public health cooperation workforces combining epidemiologic and genomic data to monitor the viral spread throughout this kind of highly permeable dry frontiers around the world.

13.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-158006

Résumé

Despite all efforts to control the COVID-19 spread, the SARS-CoV-2 reached South America within three months after its first detection in China, and Brazil became one of the hotspots of COVID-19 in the world. Several SARS-CoV-2 lineages have been identified and some local clusters have been described in this early pandemic phase in Western countries. Here we investigated the genetic diversity of SARS-CoV-2 during the early phase (late February to late April) of the epidemic in Brazil. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. This SARS-CoV-2 Brazilian lineage was probably established during February 2020 and rapidly spread through the country, reaching different Brazilian regions by the middle of March 2020. Our study also supports occasional exportations of this Brazilian B.1.1 lineage to neighboring South American countries and to more distant countries before the implementation of international air travels restrictions in Brazil.

14.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20073007

Résumé

The SARS-CoV-2 rapidly spread around the world during 2020, but the precise time in which the virus began to spread locally is currently unknown for most countries. Here, we estimate the probable onset date of the community spread of SARS-CoV-2 from the cumulative number of deaths reported during the early stage of the epidemic in Western Europe and the Americas. Our results support that SARS-CoV-2 probably started to spread locally in all western countries analyzed between the middle of January and early February 2020, thus long before community transmission was officially recognized and control measures were implemented.

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