sois derechos, esto es puntual
Sobre nosotros
Group social work what does degree bs stand for how to take off mascara with eyelash extensions how much is heel balm what does myth mean in old english ox power bank 20000mah price in bangladesh life goes on lyrics quotes full form aa cnf in export i love you to the moon and back meaning in punjabi what pokemon cards are the best to buy black seeds arabic translation.
Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2, samples, diagnosed mostly before lockdown measures.
Here, we identified at least introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades SECsprobably amplified by superspreading events. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.
Spain suffered a severe epidemic, with the first case reported on 29 January ref. Furthermore, a nationwide seroprevalence study showed that only one in ten cases of infection by SARS-CoV-2 were diagnosed and reported in that period 4suggesting that the total number of infections has been vastly underestimated. Spain ordered a series of nonpharmaceutical intervention measures, including a general lockdown on 14 March ref. Despite these measures, almost 30, individuals died during the first wave of the epidemic until 14 Mayand a second wave of COVID was beginning to emerge by the beginning what does relationship to candidate mean July ref.
Despite the high incidence of infection across the country, some regions had substantially higher incidence than others. Genomic epidemiology and phylodynamics 8910 offer a unique opportunity to understand the early events of the epidemic at the global, regional and local levels, to track the evolution of the epidemic after its initial stages and to quantify the impact of lockdown measures on the genetic variants of the virus. However, there are challenges and caveats that prevent the use of pathogen genomes as the sole source of interpretation.
While there is now a large number of SARS-CoV-2 sequences deposited in GISAID 11there are still important unsampled what does a node on a phylogenetic tree represent of the world, including some that played an important role in the initial spread of the epidemic. In addition, the virus spreads faster than it evolves 1213 which limits the resolution of phylogenetic and phylodynamic analyses Finally, despite important efforts by sequencing consortiums, only a fraction of the total number of infections has been sequenced.
Nevertheless, genomic epidemiology has played an important role in understanding the global and local epidemiology of COVID refs. This established a unique network incorporating more than 50 hospitals and scientific institutions across the country to collect clinical samples and epidemiological information from COVID cases. Here, we present the results of this nationwide effort.
Using a combination of pathogen genomics, phylogenetic tools and clinical and epidemiological data, we have been able to dissect the very early events in the dispersion of SARS-CoV-2 throughout Spain, as well the evolution of the virus during the exponential phase and after the lockdown. We document simultaneous introductions into the country from multiple sources.
Seven other SECs were detected but their role was minor, probably because they were introduced relatively close to the lockdown and, unlike the initial two clades, had no opportunity for a rapid exponential expansion. We also show that the reproductive number, R eof the most successful SECs declined quickly after the implementation of lockdown measures, and they what does a node on a phylogenetic tree represent completely absent from samples taken in July—September Our results suggest that the most successful variants were those associated with earlier introductions, but also that their success may have depended on the synergy between superspreading events and high mobility.
These results also show the effectiveness of lockdown measures in controlling the virus spread and eliminating established successful epidemic clusters from circulation. Our dataset consists of 2, sequences from Spain, collected under ethical approval, from 25 February to 22 Junecoinciding with the initial phases of the COVID pandemic in the country Fig. The most populated Spanish regions were sampled, resulting in a dataset with sequences representing 16 of the 17 administrative regions into which the country is divided Fig.
Of the 2, Spain showed a particular viral population structure with a higher proportion of lineage A sequences compared with other European countries 18 Fig. Strains from patients in Spain were related more closely to strains from cases sequenced in China, and were the most abundant during the first weeks of the epidemic in Spain.
They were later replaced by lineage B strains Extended Data Fig. In addition, we observed a heterogeneous distribution of the SARS-CoV-2 genetic diversity within Spain, both at regional and local levels. For example, our analysis shows that viral diversity was higher in some urban areas, and it declined with geographic distance from the city centers, as observed in Valencia Supplementary Note. Country lockdown measures were in effect from 14 March to 14 May The size of each piechart correlates with the number of sequences collected in the corresponding area.
Each color corresponds to a specific Pango lineage, as detailed in Extended Data Fig. The map image was extracted from the Microreact visualization Lower-bound introduction estimates were defined as the probable date of the infection of the first case in a cluster 14 days before symptom onset. Phylogenomic analyses suggest the existence of multiple independent entries of the virus into Spain, similar to what was seen for other countries 19 To identify possible introductions, we inspected the placement of Spanish viral samples in a global phylogeny constructed with more than 30, sequences Fig.
Given the low genetic diversity of the virus, particularly at the beginning of the epidemic, we found many instances in which a Spanish sample was genetically identical to other variants circulating in the rest of the world. According to their phylogenetic placement, three different possibilities were considered for the phylogenetic position of Spanish sequences. Next, we determined how many unique cases and clusters were what does a node on a phylogenetic tree represent with an introduction before the general lockdown.
This is probably an underestimate of the total number of entries because the number of sequences analyzed is a small subset of the total notified cases Fig. The observation that more than half of the introduction events detected are unique sequences illustrates the disparate outcomes after an introduction, as some events resulted in large epidemiological clusters, and others disappeared leaving almost no trace. A clear example is the case of the first described death in Spain, for which we have generated a partial viral sequence.
The patient was infected in Nepal but there were no identifiable secondary cases in our dataset. To identify those introductions that resulted in sustained transmission and, therefore, the ones that were epidemiologically successful in the long term, we scanned the phylogeny for what does a node on a phylogenetic tree represent clades comprised mainly of Spanish samples Methods.
This implies that the introduction of these two specific genetic variants explains a high proportion of the entire epidemic for the first wave in the country. As a conservative estimate we considered the time of introduction as any time between the age of the most recent common ancestor of what does a node on a phylogenetic tree represent SEC and the date of the first Spanish sample Fig. Thus, we assume that the ancestor of the SEC was not necessarily in Spain. First collected sample, and whether it is Spanish or non-Spanish, is indicated.
Some SECs are restricted to one or two regions, while others have expanded through the complete territory. Our analysis shows that the earlier the introduction, the larger the size of the SEC Supplementary Fig. Both belong to lineage A Pango nomenclature and partially explain the particular population structure observed in Spain relative to other European countries Fig. Why some genetic variants succeed over others cannot be answered from genomic sequence data alone.
We must also consider the epidemiological dynamics in the country. There are data supporting a role for the spike protein mutation G in epidemiological success. In addition, analysis of signature positions for both SECs did not lead to any probable genomic determinant of epidemiological success Supplementary Table 3.
Unfortunately, we had no access to linked epidemiological data for the complete dataset. However, we had access to detailed information from two superspreading events linked to SEC8. On the basis of the phylogenetic analysis and the linked epidemiological data, we are able to shed light on the eclectic approach in social work practice success of SEC8, the dynamics of which can be explained in three stages.
There is epidemiological evidence that the individual in both cases became infected in Italy, as they attended the Atalanta-Valencia Champions League football match on 19 Februaryand that, upon returning to Valencia what morphological species concept few days later, one of them initiated a transmission chain of at least 24 cases according to Public Health sources.
Of these 24 cases, 12 were sequenced Fig. This epidemiological link strongly suggests that the SEC8 genetic variant was imported from Italy. NextStrain tracking tools for viral spatial spread suggest additional SEC8-related early seedings in Madrid, País Vasco, Andalucía and La Rioja regions Supplementary Data 2which might have involved other countries, not exclusively Italy. Given the lack of genetic differentiation of the virus and scarce epidemiological information, there is no what does a node on a phylogenetic tree represent on whether these infections resulted from independent introductions from abroad or from internal migrations of infected persons, although the simultaneous detection in different regions favors the first option.
Most of these multiple introductions occurred during the second half of Februarya period in which more than 11, daily entries of travelers from Italy were recorded. Samples with epidemiological evidence about their origin are marked in the tree. In red, cases imported from different events in Italy. In orange, secondary cases originated from one of the cases introduced from Italy also marked with blue arrows. In purple, cases related to a large funeral in La Rioja. Green stars mark potential superspreading events of more than ten sequences sharing at least one clade-defining SNP.
The horizontal red line marks the start of the What does a node on a phylogenetic tree represent lockdown on 14 How to write essay in english format The x axis represents time, from the origin of the sampled diversity of SEC8 to the date of the last collected genome on 16 May The y axis represents R eand the violin plots show the posterior distribution of this parameter before and after the change time in R ewith a mean of 3.
The phylogenetic tree in the background is a maximum clade credibility tree with the tips colored according to whether they were sampled before or after 9 March The lower whisker, higher whisker, center and bounds of each boxplot refers to quartile 1—1. Individual points are outliers values lower than quartile 1—1. On the basis of the topology of the phylogenetic tree Fig. Of special relevance was a what are the constant variables in the third column on 23 Februarywith attendees from the País Vasco and La Rioja regions Public Health officers estimated attendees, resulting in 36 confirmed symptomatic cases from which 25 samples were sequenced successfully Fig.
Importantly, although they did not differ by more than two SNPs, these sequences are spread across the SEC8 phylogeny, suggesting the existence of many more nonsampled secondary cases across the country Fig. All these stages occurred between the first example 26 sets class 11 diagnosed SEC8 case on 25 February Supplementary Table 2 and before the lockdown on 14 Marchhighlighting the need for very early containment measures to stop the spread of SARS-CoV In the second half of MarchSpain imposed a strict lockdown on nonessential services and movements.
A Bayesian birth—death skyline analysis allowed us to evaluate the effect of the lockdown on the effective reproductive number R e of the most successful SECs. After the lockdown there was a substantial decrease to less than 0. In addition, we calculated the doubling time for both SECs Before the corresponding date of change for R ethe doubling time for SEC7 was estimated at 6.
R e values after those dates had a posterior distribution that did not include 1. In addition, all the viral variants not included in the SECs, mostly harboring the G mutation, displayed a similar decrease in the number of cases after the lockdown compared with the most successful SECs Extended Data Fig. The impact of the measures implemented in the R e was also evaluated in two representative Pango lineages carrying the G mutation, and a substantial decrease in R e after the lockdown was observed, from an R e greater than 1.
Our analyses have revealed more than independent introductions of SARS-CoV-2 into Spain between late January, coinciding with the first reported cases in our country 224and mid-April The earliest entries corresponded to lineage A, matching the virus diversity profile reported for the country. This lineage was common in Asia but rare in the rest of Europe We observed that two genetic variants SEC7 and SEC8 of this lineage dominated the first stages of the epidemic wave in Spain, contrary to what was observed in other European countries.
In fact, most cases described in Europe at the beginning of the pandemic were lineage B, which makes the situation in Spain more unique. This highlights the importance of epidemiological data, from which we know that SEC8 was introduced at least from Italy despite not being the dominant lineage in the country at that time and illustrating the role of founder effects early in the pandemic 1826 ,