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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">It is well-documented that genetic expression is the most complex and varied process in the various animal viruses<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; It is an issue of special focus for virologists and as a consequence&#44; it is one of the most studied and better-defined areas&#44; with widespread repercussions on clinical pathology&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Viruses develop a multitude of strategies to achieve the expression of their genes and efficient replication of their genomes&#46; To do so&#44; they depend on the possibilities offered by the parasitized cells<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; From a practical point of view&#44; they have short generation times and&#44; at least in the case of RNA viruses&#44; have replication enzymes that are prone to making mistakes&#46; In consequence&#44; they evolve much more quickly than other organisms&#44; which provides unique opportunities to study changes in circulating virus populations<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Though SARS-CoV-2 undergoes mutations every time it performs an intracellular replication process&#44; the stability of its sequence is greater than that of other riboviria because it has an intrinsic error correction mechanism&#46; This is based on a protein codified in the ORF1ab gene called nsp14 &#40;ExoN&#41;&#44; with 3&#8242;&#8211;5&#8242; exonuclease activity that maintains stability of the virus genome by minimizing modifications&#46; Therefore&#44; coronaviruses generally accumulate mutations much more slowly than other RNA viruses<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; Even still&#44; genomic variation regarding complete genomes&#44; analyzed according to place and time&#44; allow for analyzing the chain of transmission of isolates&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the process of host cell recognition&#44; SARS-CoV-2 uses the S protein&#44; which binds to the host cell&#8217;s angiotensin-converting enzyme 2 receptor<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; In addition&#44; this protein&#44; and in particular the S1 subunit&#44; has a receptor-binding domain that is an essential element with regard to inducing an immune response to both natural infection and vaccination strategies<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; It has been noted that variability in the gene that codifies this protein would affect both vaccine effectiveness&#44; the response to the use of monoclonal antibody therapies&#44; and innate immunity<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The study of evolution by means of SARS-CoV-2 genome sequencing in order to quickly identify substitutions&#44; insertions&#44; or deletions that may induce a change in viral behavior is an essential task in monitoring the pandemic and its consequences for clinical management and the approach to prevention&#46; This task includes at least five areas<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">First&#44; it is important to describe phenotypic modifications that lend the virus greater capacity for transmission and&#44; in consequence&#44; increase the speed of its spread&#46; Second&#44; it is necessary to determine its pathogenic power in terms of severity and thus define its potential to cause not only infection&#44; but also to cause disease and lead to severe illness and death&#46; Third&#44; its interference in the immune response after natural infection and in various vaccination models should be defined&#46; Fourth&#44; it should be evaluated whether they entail some type of change in the use of diagnostic tests&#44; whether these tests are direct&#44; based on antigen detection or molecular techniques&#44; or indirect&#44; which indicate the innate or adaptive response&#46; Lastly&#44; its repercussions on treatment with antivirals or monoclonal antibodies prescribed to those infected or those who have the disease should be established&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A temporal description of virus mutations in different geographical areas can contribute to monitoring its propagation and determining possible routes and dynamics of transmission&#46; It is possible to reconstruct a pathogen&#8217;s evolutionary history by means of phylogenetic and phylodynamic studies that generate information which serve to guide the healthcare response to epidemic outbreaks and pandemics&#46; In this scenario&#44; massive sequencing and bioinformatics emerge as essential elements for its study<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">After having designated variants in accordance with their geographical origin&#44; in order not to stigmatize countries or areas of the planet&#44; an agreement was adopted to establish their names using letters of the Greek alphabet<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#44; as is done in other sciences&#46; Thirteen variants have been designated to date&#58; alpha &#40;B&#46;1&#46;1&#46;7&#41;&#44; beta &#40;B&#46;1&#46;351&#41;&#44; gamma &#40;P&#46;1&#41;&#44; delta &#40;B&#46;1&#46;617&#46;2&#41;&#44; epsilon &#40;B&#46;1&#46;427&#47;B&#46;1&#46;429&#41;&#44; zeta &#40;P&#46;2&#41;&#44; eta &#40;B&#46;1&#46;525&#41;&#44; theta &#40;P&#46;3&#41;&#44; iota &#40;B&#46;1&#46;526&#41;&#44; kappa &#40;B&#46;1&#46;617&#46;1&#41;&#44; lambda &#40;<span class="elsevierStyleSmallCaps">C</span>&#46;37&#41;&#44; mu &#40;B&#46;1&#46;621&#41;&#44; and omicron &#40;B&#46;1&#46;1&#46;529&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The first recognized variant appeared in September 2020 and was designated the British or alpha variant &#40;B&#46;1&#46;1&#46;7&#41;&#46; It was described as a &#8220;variant of concern&#8221; &#40;VOC&#41; on December 18&#44; 2020&#46; Two other variants from Commonwealth countries caused high levels of concern&#46; They are the South African or beta variant &#40;B&#46;1&#46;351&#41;&#44; which was detected in May 2020 and designated a VOC on January 14&#44; 2021&#44; and the first Indian or delta &#40;B&#46;1&#46;617&#46;2&#41; variant&#44; which was detected in October 2020 and designated a VOC on May 6&#44; 2021&#46; It displaced the alpha variant in our country during the summer of 2021 and became responsible for practically 100&#37; of cases&#46; In addition to these three VOC&#44; the Brazilian or gamma variant &#40;P&#46;1&#41;&#44; first detected on January 6&#44; 2021&#44; merits mention&#46; It has not spread as extensively worldwide and is the only one of these four that had its origin outside of countries of British influence&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The new South African strain called omicron &#40;B&#46;1&#46;1&#46;529&#41; emerged on November 9&#44; 2021 and was designated a VOC by the WHO on November 24&#46; Experts predict its spread given the large number of mutations that have accumulated in the gene that codes the spike &#40;between 26 and 32&#41;&#46; In this regard&#44; it must be clarified that although a set of mutations defines a line&#44; different genomes of a single strain contain mutations that differentiate them&#46; In fact&#44; two sublines of this new omicron variant have already been proposed&#58; BA&#46;1 and BA&#46;2&#44; with 20 and 27 characteristic mutations&#44; respectively&#46; It is notable that the new BA&#46;2 subline does not have the 69&#47;70del deletion and therefore&#44; it is not detectable due to a failure in the S gene target used in the PCR detection system&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Though it is true that the importance of this new variant will be determined by the repercussion it has on the five aforementioned areas&#44; the real evaluation of its impact on the disease and public health requires a certain amount of time and the launch of cohort studies that allow for adding knowledge in this field&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Meanwhile&#44; in our setting&#44; continuing with established vaccination plans and maintaining the healthcare measures of precaution&#44; social distancing&#44; and healthcare where required will be decisive<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; At the same time&#44; we must not overlook the profound changes in the composition of the virus&#8217; 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Editorial
The evolution of SARS-CoV-2 variants and their clinical and healthcare implications
La evolución en variantes del SARS-CoV-2 y su repercusión clínica y sanitaria
J.M. Eirosa,
Corresponding author
jmeiros@uva.es

Corresponding author.
, M. Hernándezb
a Servicio de Microbiología, Área de Microbiología, Hospital Universitario Río Hortega, Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain
b Laboratorio de Biología Molecular y Microbiología, Instituto Tecnológico Agrario de Castilla y León, Valladolid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">It is well-documented that genetic expression is the most complex and varied process in the various animal viruses<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; It is an issue of special focus for virologists and as a consequence&#44; it is one of the most studied and better-defined areas&#44; with widespread repercussions on clinical pathology&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Viruses develop a multitude of strategies to achieve the expression of their genes and efficient replication of their genomes&#46; To do so&#44; they depend on the possibilities offered by the parasitized cells<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>&#46; From a practical point of view&#44; they have short generation times and&#44; at least in the case of RNA viruses&#44; have replication enzymes that are prone to making mistakes&#46; In consequence&#44; they evolve much more quickly than other organisms&#44; which provides unique opportunities to study changes in circulating virus populations<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Though SARS-CoV-2 undergoes mutations every time it performs an intracellular replication process&#44; the stability of its sequence is greater than that of other riboviria because it has an intrinsic error correction mechanism&#46; This is based on a protein codified in the ORF1ab gene called nsp14 &#40;ExoN&#41;&#44; with 3&#8242;&#8211;5&#8242; exonuclease activity that maintains stability of the virus genome by minimizing modifications&#46; Therefore&#44; coronaviruses generally accumulate mutations much more slowly than other RNA viruses<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; Even still&#44; genomic variation regarding complete genomes&#44; analyzed according to place and time&#44; allow for analyzing the chain of transmission of isolates&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In the process of host cell recognition&#44; SARS-CoV-2 uses the S protein&#44; which binds to the host cell&#8217;s angiotensin-converting enzyme 2 receptor<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; In addition&#44; this protein&#44; and in particular the S1 subunit&#44; has a receptor-binding domain that is an essential element with regard to inducing an immune response to both natural infection and vaccination strategies<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a>&#46; It has been noted that variability in the gene that codifies this protein would affect both vaccine effectiveness&#44; the response to the use of monoclonal antibody therapies&#44; and innate immunity<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The study of evolution by means of SARS-CoV-2 genome sequencing in order to quickly identify substitutions&#44; insertions&#44; or deletions that may induce a change in viral behavior is an essential task in monitoring the pandemic and its consequences for clinical management and the approach to prevention&#46; This task includes at least five areas<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">First&#44; it is important to describe phenotypic modifications that lend the virus greater capacity for transmission and&#44; in consequence&#44; increase the speed of its spread&#46; Second&#44; it is necessary to determine its pathogenic power in terms of severity and thus define its potential to cause not only infection&#44; but also to cause disease and lead to severe illness and death&#46; Third&#44; its interference in the immune response after natural infection and in various vaccination models should be defined&#46; Fourth&#44; it should be evaluated whether they entail some type of change in the use of diagnostic tests&#44; whether these tests are direct&#44; based on antigen detection or molecular techniques&#44; or indirect&#44; which indicate the innate or adaptive response&#46; Lastly&#44; its repercussions on treatment with antivirals or monoclonal antibodies prescribed to those infected or those who have the disease should be established&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A temporal description of virus mutations in different geographical areas can contribute to monitoring its propagation and determining possible routes and dynamics of transmission&#46; It is possible to reconstruct a pathogen&#8217;s evolutionary history by means of phylogenetic and phylodynamic studies that generate information which serve to guide the healthcare response to epidemic outbreaks and pandemics&#46; In this scenario&#44; massive sequencing and bioinformatics emerge as essential elements for its study<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">After having designated variants in accordance with their geographical origin&#44; in order not to stigmatize countries or areas of the planet&#44; an agreement was adopted to establish their names using letters of the Greek alphabet<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#44; as is done in other sciences&#46; Thirteen variants have been designated to date&#58; alpha &#40;B&#46;1&#46;1&#46;7&#41;&#44; beta &#40;B&#46;1&#46;351&#41;&#44; gamma &#40;P&#46;1&#41;&#44; delta &#40;B&#46;1&#46;617&#46;2&#41;&#44; epsilon &#40;B&#46;1&#46;427&#47;B&#46;1&#46;429&#41;&#44; zeta &#40;P&#46;2&#41;&#44; eta &#40;B&#46;1&#46;525&#41;&#44; theta &#40;P&#46;3&#41;&#44; iota &#40;B&#46;1&#46;526&#41;&#44; kappa &#40;B&#46;1&#46;617&#46;1&#41;&#44; lambda &#40;<span class="elsevierStyleSmallCaps">C</span>&#46;37&#41;&#44; mu &#40;B&#46;1&#46;621&#41;&#44; and omicron &#40;B&#46;1&#46;1&#46;529&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The first recognized variant appeared in September 2020 and was designated the British or alpha variant &#40;B&#46;1&#46;1&#46;7&#41;&#46; It was described as a &#8220;variant of concern&#8221; &#40;VOC&#41; on December 18&#44; 2020&#46; Two other variants from Commonwealth countries caused high levels of concern&#46; They are the South African or beta variant &#40;B&#46;1&#46;351&#41;&#44; which was detected in May 2020 and designated a VOC on January 14&#44; 2021&#44; and the first Indian or delta &#40;B&#46;1&#46;617&#46;2&#41; variant&#44; which was detected in October 2020 and designated a VOC on May 6&#44; 2021&#46; It displaced the alpha variant in our country during the summer of 2021 and became responsible for practically 100&#37; of cases&#46; In addition to these three VOC&#44; the Brazilian or gamma variant &#40;P&#46;1&#41;&#44; first detected on January 6&#44; 2021&#44; merits mention&#46; It has not spread as extensively worldwide and is the only one of these four that had its origin outside of countries of British influence&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The new South African strain called omicron &#40;B&#46;1&#46;1&#46;529&#41; emerged on November 9&#44; 2021 and was designated a VOC by the WHO on November 24&#46; Experts predict its spread given the large number of mutations that have accumulated in the gene that codes the spike &#40;between 26 and 32&#41;&#46; In this regard&#44; it must be clarified that although a set of mutations defines a line&#44; different genomes of a single strain contain mutations that differentiate them&#46; In fact&#44; two sublines of this new omicron variant have already been proposed&#58; BA&#46;1 and BA&#46;2&#44; with 20 and 27 characteristic mutations&#44; respectively&#46; It is notable that the new BA&#46;2 subline does not have the 69&#47;70del deletion and therefore&#44; it is not detectable due to a failure in the S gene target used in the PCR detection system&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Though it is true that the importance of this new variant will be determined by the repercussion it has on the five aforementioned areas&#44; the real evaluation of its impact on the disease and public health requires a certain amount of time and the launch of cohort studies that allow for adding knowledge in this field&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Meanwhile&#44; in our setting&#44; continuing with established vaccination plans and maintaining the healthcare measures of precaution&#44; social distancing&#44; and healthcare where required will be decisive<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46; At the same time&#44; we must not overlook the profound changes in the composition of the virus&#8217; genome that condition its structure and functionality&#44; given that they will cause the current vaccines and acquired immunity to lose effectiveness<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46; Therefore&#44; it is necessary to minimize virus replication by limiting new infections&#44; maintain virological surveillance of cases by means of massive sequencing and reporting of the results<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#44; and promote the development of effective antiviral treatments as much as possible&#46;</p></span>"
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ISSN: 22548874
Original language: English
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