SARS-CoV-2 variants, a still unfinished story

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Although the SARS-CoV-2 genome appears relatively stable&#44; this type of single-stranded RNA virus accumulates an estimated mutation rate of around 10<span class="elsevierStyleSup">&#8722;6</span>&#8211;10<span class="elsevierStyleSup">&#8722;4</span> per replicative cycle&#46; These mutations can affect the interaction of the spike antigen &#40;S&#41; with the host cellular receptor &#40;angiotensin-converting enzyme 2 &#91;ACE2&#93;&#41;&#44; affecting susceptibility to immune response&#44; the aggressiveness of the infection&#44; and&#47;or the transmission capacity of the virus&#46; Thus&#44; some mutations may confer evolutionary advantages that favour the selection of certain lineages or variants&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Variants can appear from genetic deletions &#40;characterised by the loss of a portion of the nucleic acid sequence&#41;&#44; synonymous mutations &#40;also known as silent or nonsense mutations&#44; which do not cause changes in amino acid synthesis&#41; or non-synonymous mutations &#40;associated with a change in amino acid coding&#41;&#46; The latter are the most relevant functionally&#46; Mutations that are termed &#8220;escape&#8221; subsequently expand under selective immunological pressure that limits&#44; but does not eliminate&#44; replication&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Different variants have emerged in recent months that are co-circulating worldwide&#44; and new variants are predicted to continue to emerge in the future&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises the main SARS-COV-2 variants currently circulating&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Nomenclature</span><p id="par0015" class="elsevierStylePara elsevierViewall">Although the terms strain and variant are usually used synonymously after mutations have occurred&#44; in a pure sense they should cover the induction or otherwise of changes in the behaviour of the virus&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> However&#44; these terms will be used interchangeably in this text&#46; The nomenclature of the different variants of SARS-CoV-2 that have gradually emerged uses a &#8220;colloquial&#8221; form that usually refers to the country or place where the variant was detected &#40;British strain&#41;&#44; a code from the Pangolin database<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> &#40;B&#46;1&#46;1&#46;7&#41;&#44; and one based on the Nextstrain page<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> &#40;20I&#47;501Y&#46;V1&#41;&#46; This multiple system can often lead to confusion&#46; To provide information&#44; the World Health Organisation &#40;WHO&#41; very recently adopted a simpler system based on letters of the Greek alphabet to denote the various variants&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the new nomenclature for the different variants&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The different mutations associated with changes in amino acids are named with an alpha-numeric key that indicates&#44; firstly&#44; the code of a capital letter of the amino acid that has been replaced&#44; a number that refers to the position of the change and finally the capital letter corresponding to the code of the new amino acid&#46; Thus&#44; for example&#44; the mutation N501Y indicates that the amino acid asparagine &#40;N&#41; has been replaced by a tyrosine &#40;Y&#41; at position 501&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Classification of the SARS-CoV-2 variants</span><p id="par0025" class="elsevierStylePara elsevierViewall">The different SARS-CoV-2 variants have been classified according to their level of importance<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#58;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Variants of Interest &#40;VOI&#41; are those that have been associated with changes to receptor binding&#44; reduced neutralisation by antibodies generated against previous natural infection or vaccination&#44; reduced efficacy of treatments&#44; potential diagnostic impact&#44; or predicted increase in transmissibility and&#47;or disease severity&#44; with clusters of cases and outbreaks&#44; but with limited prevalence in other countries&#46; Examples of variants of interest are B&#46;1&#46;525 &#40;20A&#47;S&#58;484K&#41; B&#46;1&#46;526 &#40;20C&#47;S&#58;484K&#41;&#44; B&#46;1&#46;526&#46;1 &#40;20C&#41;&#44; B&#46;1&#46;617 &#40;20A&#41;&#44; B&#46;1&#46;617&#46;1 &#40;20A&#47;S&#58;154K&#41;&#44; B&#46;1&#46;617&#46;2 &#40;20A&#47;S&#58;478K&#41;&#44; B&#46;1&#46;617&#46;3 &#40;20A&#41;&#44; and P&#46;2 &#40;20J&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Variants of Concern &#40;VOC&#41; include variants where there is evidence of an increase in transmissibility&#44; severity&#44; reduction in neutralisation by natural antibodies or those generated by vaccination&#44; reduced effectiveness of treatments or diagnostic test failures&#46; Examples of variants of concern are the British B&#46;1&#46;1&#46;7 &#40;20I&#47;501Y&#46;V1&#41;&#44; the South African B&#46;1&#46;351 &#40;20H&#47;501&#46;V2&#41;&#44; the Brazilian P&#46;1 &#40;20J&#47;501Y&#46;V3&#41;&#44; the Californian B&#46;1&#46;427 &#40;20C&#47;S&#58;452R&#41; and the Californian B&#46;1&#46;429 &#40;20C&#47;S&#58;452R&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Variants of High Consequence &#40;VOHC&#41; include those for which there is clear evidence that prevention and therapeutic measures have significantly reduced effectiveness relative to previously circulating variants&#46; Fortunately&#44; at present&#44; there are no known SARS-CoV-2 variants that fall into this category&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The European Centre for Disease Prevention and Control &#40;ECDC&#41; envisages an additional category&#44; termed variants under monitoring&#44; for those with similar properties to variants of concern&#44; but for which there is only preliminary scientific evidence&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Wild type strain</span><p id="par0050" class="elsevierStylePara elsevierViewall">The original strain that started the COVID-19 pandemic in 2020 carried the 484E mutation&#46; This mutation is located in the epitope of the dominant region encoding the S protein&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Between January and February 2020&#44; a SARS-CoV-2 variant emerged with a D614G substitution in the gene encoding the S protein&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The original strain had the 614D precursor&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> This D614G mutation in the wild type strain enhanced its ability to drive the pandemic&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Over a period of several months the D614G mutant strain replaced the strain initially identified in China and by June 2020 it had become dominant&#46; This strain&#44; compared to its precursor&#44; showed increased infectivity and transmissibility&#46; However&#44; it was not associated with increased severity&#44; impaired effectiveness of laboratory diagnostic tests&#44; decreased neutralising capacity of antibodies or reduced therapeutic effectiveness&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">British variant</span><p id="par0055" class="elsevierStylePara elsevierViewall">The variant termed the British B&#46;1&#46;1&#46;7 &#40;20I&#47;501Y&#46;V1&#41; was detected at the end of 2020 in the UK and has rapidly spread to many countries&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> often supplanting the original wild type strain&#46; It has more than 20 mutations&#44; excluding those not associated with changes in amino acids&#44; almost half of which affect the S antigen coding regions &#40;the main target of neutralising antibodies&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> This variant maintains the D614G mutation and also shows the N501Y mutation that seems to increase the interaction of the S protein with the ACE2 receptor<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> as it affects the receptor binding domain &#40;RBD&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In addition&#44; it has the 69&#47;70 deletion&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;16</span></a> This deletion may decrease the diagnostic sensitivity of certain PCR tests that target the gene coding for the S antigen&#46; However&#44; since most PCR techniques combine multiple targets&#44; this may not be too problematic&#46; These molecular changes seem not to impact the performance of rapid antigen tests&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> This variant has been associated with increased transmissibility and severity&#46; Although the increased clinical severity of this and other variants may be questionable&#44;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;17</span></a> the increased mortality reported for this strain is 4&#46;1 deaths per 1000 cases detected &#40;compared to that of previously circulating strains estimated at 2&#46;5 per 1000 cases&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and it shows relative resistance to neutralisation by monoclonal antibodies to the S antigen&#46; However&#44; it is not more resistant to plasma from individuals exposed to natural infection or following vaccination&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">South African variant</span><p id="par0060" class="elsevierStylePara elsevierViewall">The B&#46;1&#46;351 variant &#40;20H&#47;501&#46;V2&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;13&#44;15</span></a> which may have appeared a few months earlier&#44; was reported in South Africa in December 2020&#46; This variant&#44; which emerged independently of B&#46;1&#46;1&#46;7&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> harbours several non-synonymous mutations and a deletion that mostly affects the S protein&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> It combines the D614G and N501Y<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> mutations with the K417N&#44; E484K<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> mutations&#46; Unlike the British strain&#44; it does not carry the 69&#47;70 deletion&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The N501Y mutation in the South African variant&#44; although also present in the UK variant&#44; appears to be phylogenetically distinct&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> There is uncertainty as to whether it is associated with greater severity or worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Compared to the wild type strain&#44; it appears to be markedly more resistant to neutralisation by serum from convalescent or vaccinated subjects&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;21&#44;22</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Brazilian variant</span><p id="par0065" class="elsevierStylePara elsevierViewall">The Brazilian variant P&#46;1 &#40;B&#46;1&#46;1&#46;28&#46;1&#44; 20J&#47;501Y&#46;V3&#41;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> was detected in Japan from travellers from Brazil&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> It contains several mutations&#44; including three affecting the S protein&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;16</span></a> The E484K mutation&#44; shared by both the Brazilian and South African variants&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> has triggered alarm due to its possible link to some immune evasiveness&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Both variants have been associated with increased transmissibility and a higher reinfection rate&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> The other two mutations of this variant that affect the S protein are K417T and N501Y&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> A way of distinguishing the South African variant from the Brazilian variant is that the Brazilian variant lacks the K417N mutation&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">B&#46;1&#46;1&#46;7 variant with E484K mutation</span><p id="par0070" class="elsevierStylePara elsevierViewall">The detection of the E484K mutation in B1&#46;1&#46;7&#46; sequences has also raised concerns about a loss of vaccine efficacy&#44; due to its combination with the other mutations of the British variant&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Californian variant</span><p id="par0075" class="elsevierStylePara elsevierViewall">Other emerging variants include strain B&#46;1&#46;429 &#40;20C&#47;S&#58;452R&#41;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;24&#44;25</span></a> and B&#46;1&#46;427 &#40;20C&#47;S&#58;452R&#41;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> circulating in California&#46; The B&#46;1&#46;429 variant&#44; which has the L452R&#44; D614G and W152C<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;25</span></a> mutations&#44; among others&#44; has spread rapidly in the US and other countries&#44; and is less susceptible to neutralisation by serum from convalescent or vaccinated subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> These variants have been classified as variants of concern by the CDC &#40;Centres for Disease Control and Prevention&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> whereas the WHO considers them only variants of interest&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Indian variant</span><p id="par0080" class="elsevierStylePara elsevierViewall">More recently&#44; there has been widespread alarm about the emergence and spread in India of the new variant B&#46;1&#46;617&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> also known as VUI &#40;Variant Under Investigation&#41;-21APR-01<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a> and 20A according to &#8220;Nextstrain&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> It is considered a variant of interest for the time being&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Some media are reporting this strain as a &#8220;double mutant&#8221; because it combines the L452R mutations of the California strain with the E484Q mutation&#46; The term &#8220;double mutant&#8221; is meaningless considering that the other SARS-CoV-2 variants also carry several mutations simultaneously&#46; Other related lineages are B&#46;1&#46;617&#46;1 &#40;20A&#47;S&#58;154K&#41;&#44; B&#46;1&#46;617&#46;2 &#40;20A&#47;S&#58;478K&#41;&#44; and B&#46;1&#46;617&#46;3 &#40;20A&#41;&#46; These three lineages have the L452R mutation in common&#46; The variants B&#46;1&#46;617&#46;1 and B&#46;1&#46;617&#46;3 &#40;both considered variants of interest by the CDC and the ECDC&#41;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> share the E484Q<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> mutation with B&#46;1&#46;617&#46; The B&#46;1&#46;617&#46;2 variant&#44; although still classified as a variant of interest by the CDC&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> has recently been considered a variant of concern by the ECDC&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">It is thought that mutations in the S protein&#44; which increase the transmissibility of the virus&#44; could favour replacement of wild type precursor strains by the new variants already circulating and by potential future mutations&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Variants and vaccination</span><p id="par0090" class="elsevierStylePara elsevierViewall">The impact of these variants on global vaccination programmes has raised concerns and the development of markers that correlate vaccine and protection is considered a priority&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> As we mention above&#44; it has been suggested that the new variants could escape the immune response more easily&#46; In general&#44; it is considered that since the vaccine-evoked response to the S antigen targets the entire protein and mutations only affect specific regions&#44; it does not appear that the new variants can completely evade the action generated after vaccination&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The results of immunisation in Israel are encouraging in this regard&#44; where the British variant is predominant&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Preliminary trials have also shown an acceptable vaccine-induced neutralising response to different variants&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;31&#44;32</span></a> The main SARS-CoV-2 vaccines include messenger RNA vaccines &#40;mRNA-1273&#59; Moderna and BNT162b2&#59; Pfizer&#41;&#44; vector vaccines &#40;ChAdOx1&#59; AstraZeneca and Ad26&#46;COV2&#46;S&#59; Janssen&#41;&#44; and the protein subunit vaccine NVX-CoV2373 &#40;Novavax&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Messenger RNA vaccines &#40;mRNA-1273&#59; Moderna and BNT162b2&#59; Pfizer&#41;&#44; vector vaccines &#40;ChAdOx1&#59; AstraZeneca and Ad26&#46;COV2&#46; Messenger RNA vaccines &#40;mRNA-1273&#59; Moderna and BNT162b2&#59; Pfizer&#41; appear to show only slightly lower efficacy against the UK variant&#46; However&#44; their neutralising capacity <span class="elsevierStyleItalic">is</span> significantly reduced against the South African variants and to a lesser extent against the Brazilian variant &#40;given the high titre of antibodies generated for the latter variant&#44; the decreased neutralising activity seems to have a lower impact than for the South African variant&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> It has recently been suggested that&#44; although the Indian B&#46;1&#46;617&#46;1 variant is also more resistant to neutralisation&#44; the Moderna and Pfizer messenger RNA vaccines may well retain their ability to protect against it&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> The vector vaccine ChAdOx1 &#40;AstraZeneca&#41;&#44; although it may show a limited loss of activity against the British variant&#44; maintains acceptable effectiveness against it&#46; However&#44; the efficacy of this vaccine against the South African variant seems to have been significantly reduced&#44; and its use in certain countries with a high prevalence of infection by this variant has been questioned&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> This vector vaccine&#44; despite producing an antibody response with a reduced neutralising capacity against the Indian B&#46;1&#46;617&#46;1 variant&#44; appears to maintain efficacy that limits the severity and mortality of the infection&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The vector vaccine Ad26&#46;COV2&#46;S &#40;Janssen&#41; shows less than 60&#37; efficacy for protection against moderate&#47;severe disease caused by the South African strain&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The protein subunit vaccine NVX-CoV2373 &#40;Novavax&#41; is more than 80&#37; effective against the British variant but less than 50&#37; effective against the South African variant&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The Californian variants may behave in a very similar way to the British variant towards the vaccines&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Existing data suggest that beyond the humoral immune response&#44; the cellular response is capable of recognising the new variants of SARS-CoV-2&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Thus&#44; in addition to the production of specific antibodies&#44; the vaccines could lead to the induction of a cellular response &#40;helper T cells and cytotoxic T cells&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The T-dependent immune response against the S protein of SARS-CoV-2 is characterised by high levels of interferon-gamma &#40;IFN-&#611;&#41; that can be detected by interferon-gamma release assays &#40;IGRAs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> These may be adjunct assays to determine immunostatus in the current pandemic&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Diagnosis of variants</span><p id="par0100" class="elsevierStylePara elsevierViewall">In addition to the major clinical-epidemiological implications&#44; a secondary consequence of the emergence of mutant strains is reduced performance of certain <span class="elsevierStyleItalic">in vitro</span> diagnostic tests&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Whole genome sequencing methods are the gold standard for identifying SARS-CoV-2 variants&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> However&#44; alternative&#44; simpler and faster procedures based on real-time PCR techniques to detect specific mutations have recently been developed for this purpose&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Certain combinations of mutant markers enable the main variants to be differentiated&#46; The combination 484E and 501N identifies the wild type strain&#46; The combination 484E and 501Y identifies the British strain&#46; The 484K and 501Y combination occurs concomitantly in the Brazilian and South African variants&#44; but the latter also carries the 417N mutation&#46; The Californian variants contain the L452R mutation&#46; The new Indian variants B&#46;1&#46;617&#44; B&#46;1&#46;617&#46;1 and B&#46;1&#46;617&#46;3 carry the latter mutation together with E484Q&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the mutation markers that distinguish between the most important variants&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">The mass vaccination that has begun in recent months may mark the beginning of the end of the current COVID-19 pandemic&#46; However&#44; it is foreseeable that new variants of the virus will continue to appear in the near future&#46; This means that mutations must be monitored to adapt the relevant Public Health measures&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Potential new emerging strains may entail changes in terms of their infectious capacity&#44; clinical evolution&#44; prognosis&#44; and vaccine effectiveness&#46; In the worst-case scenario&#44; we should be vigilant for the potential and feared emergence of highly significant variants &#40;as yet not identified&#41;&#46; For the time being&#44; standard preventive measures to reduce transmission&#44; based on limiting interpersonal contact and maintaining safe social distances&#44; remain in place&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Certain vaccines retain their protective efficacy against new variants and thus their extensive use can be highly successful&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">To avoid the possibility of selection of vaccine escape variants&#44; it is recommended that preparations be used that generate elevated levels of antibodies with high neutralising activity after only one dose and&#44; for vaccines that require two doses&#44; not to prolong for too long the interval between the first and second dose&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> Increasing the number of doses&#44; alternating vaccines&#44; and developing monovalent and polyvalent vaccines against different variants have been suggested as future strategies proposed for immunoprotection&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that they have received no funding for this study&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interests</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Mutations in the SARS-CoV-2 genome can affect the gene encoding the Spike &#40;S&#41; antigen&#44; which interacts with the host cell specific receptor&#44; selecting mutant variants with changes in their infective capacity&#44; pathogenic potential and resistance to neutralizing antibodies&#46; The nomenclature to design the variants uses a colloquial form referred to the country or place of detection&#44; a code from the &#8220;Pangolin&#8221; database and one from the &#8220;Nextstrain&#8221; page&#46; New variants that have spread include the British B&#46;1&#46;1&#46;7 &#40;20I&#47;501Y&#46;V1&#41;&#44; the South African B&#46;1&#46;351 &#40;20H&#47;501&#46;V2&#41;&#44; the Brazilian P&#46;1 &#40;20J&#47;501Y&#46;V3&#41;&#44; the Californians B&#46;1&#46;427 B&#46;1&#46;429 &#40;20C&#47;S&#58;452R&#41; and the most recent&#44; the Indian B&#46;1&#46;617 &#40;VUI-21APR-01&#41;&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The gold standard for the identification of the variants is whole genome sequencing&#46; However&#44; real-time PCR techniques have already been developed for the detection of specific mutations that can facilitate their presumptive identification&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The impact of these variants on global vaccination programs has raised concern&#46; It is generally thought that&#44; since the response evoked by the vaccine against the S antigen is directed at the entire protein and the mutations only affect specific regions&#44; the escape effect of the vaccine antibodies will be limited&#46; Among the future strategies proposed for immuno-protection&#44; the increase in the number of doses&#44; the alternation of vaccines and the development of specific vaccines against different variants has been suggested&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Las mutaciones en el genoma de SARS-CoV-2 pueden afectar al gen que codifica el ant&#237;geno espicular &#40;S&#41;&#44; que interact&#250;a con el receptor espec&#237;fico de la c&#233;lula hu&#233;sped&#44; seleccionando variantes mutantes con alteraciones en su capacidad infectiva&#44; potencial pat&#243;geno y resistencia a los anticuerpos neutralizantes&#46; En la nomenclatura de las variantes se utiliza una forma &#8220;coloquial&#8221; que suele hacer referencia al pa&#237;s o lugar de detecci&#243;n&#44; un c&#243;digo de la base de datos &#8220;Pangol&#237;n&#8221; y uno de la p&#225;gina &#8220;Nextstrain&#8221;&#46; Entre las nuevas variantes que se han ido propagando se incluyen la Brit&#225;nica B&#46;1&#46;1&#46;7 &#40;20I&#47;501Y&#46;V1&#41;&#44; la Sudafricana B&#46;1&#46;351 &#40;20H&#47;501&#46;V2&#41;&#44; la Brasile&#241;a P&#46;1 &#40;20J&#47;501Y&#46;V3&#41;&#44; las Californianas B&#46;1&#46;427 y B&#46;1&#46;429 &#40;20C&#47;S&#58;452R&#41; y la m&#225;s reciente&#44; la India B&#46;1&#46;617 &#40;VUI-21APR-01&#41;&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El m&#233;todo de referencia para la identificaci&#243;n de las variantes es la secuenciaci&#243;n del genoma completo&#46; Sin embargo&#44; ya se han desarrollado t&#233;cnicas de PCR en tiempo real para la detecci&#243;n de mutaciones espec&#237;ficas que pueden facilitar su identificaci&#243;n presuntiva&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El impacto de estas variantes en los programas globales de vacunaci&#243;n ha suscitado inquietud&#46; En general se piensa que&#44; dado que la respuesta evocada por la vacuna frente al ant&#237;geno S se dirige a la totalidad de la prote&#237;na y las mutaciones s&#243;lo afectan a regiones concretas&#44; el efecto de escape a los anticuerpos vacunales ser&#225; s&#243;lo limitado&#46; Entre las estrategias futuras propuestas para la inmuno-protecci&#243;n se ha sugerido el incremento del n&#250;mero de dosis&#44; la alternancia vacunal y el desarrollo de vacunas espec&#237;ficas frente a diferentes variantes&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; P&#233;rez-Abeledo M&#44; Sanz Moreno JC&#46; Variantes de SARS-CoV-2&#44; una historia todav&#237;a inacabada&#46; Vacunas&#46; 2021&#59;22&#58;167&#8211;173&#46;</p>"
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    ]
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          "tablatextoimagen" => array:1 [
            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="6" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#91;0&#44;3&#8211;8&#93;Variants</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Colloquial name&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Wild type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">British&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">South African&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Brazilian&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Californian&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Californian&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indian&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pangolin lineage name&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;351&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;427&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;429&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;617&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Name Nextstrain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20I&#47;501Y&#46;V1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20H&#47;501&#46;V2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20J&#47;501Y&#46;V3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20C&#47;S&#58;452R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20C&#47;S&#58;452R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mutations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D614G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#916;69&#47;70&#44; &#916;144 &#40;E484K<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#41;&#44; &#40;S494P<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#41;&#44; N501Y&#44; A570D&#44; D614G&#44; P681H&#44; T716I&#44; S982A&#44; D1118H &#40;K1191N<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D80A&#44; D215G&#44; &#916;241&#47;242&#47;243&#44; K417N&#44; E484K&#44; N501Y&#44; D614G&#44; A701V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L18F&#44; T20N&#44; P26S&#44; D138Y&#44; R190S&#44; K417T&#44; E484K&#44; N501Y&#44; D614G&#44; H655Y&#44; T1027I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L452R&#44; D614G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S13I&#44; W152C&#44; L452R&#44; D614G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L452R&#44; E484Q<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&#44; D614G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Associated characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37; increase in transmission capacity&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#37; increase in transmission capacity&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in convalescent and post-vaccination serum neutralisation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#37; increase in transmission capacity&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#37; increase in transmission capacity&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pending specification at the time of drafting this text&#46; Indications of increased transmissibility&#44; pathogenicity&#44; and potential reduction in post-vaccination serum neutralisation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased severity according to hospitalisation and mortality rates&#46; Minimal impact on convalescent and post-vaccination serum neutralisation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in convalescent and post-vaccination serum neutralisation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in convalescent and post-vaccination serum neutralisation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in convalescent and post-vaccination serum neutralisation&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Detected in some&#44; but not all sequences&#46;</p>"
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            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Also present in B&#46;1&#46;617&#46;1 and B&#46;1&#46;617&#46;3&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Main SARS-COV-2 variants currently circulating&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">WHO level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pangolin lineage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Nextstrain clade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GISAID clade&#47;lineage<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Variants of concern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alpha&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20I&#47;S&#58;501Y&#46;V1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GRY &#40;formerly GR&#47;501Y&#46;V1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Beta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;351&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20H&#47;S&#58;501Y&#46;V2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GH&#47;501Y&#46;V2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gamma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20J&#47;S&#58;501Y&#46;V3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GR&#47;501Y&#46;V3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Delta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;617&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21A&#47;S&#58;478K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">G&#47;452R&#46;V3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Variants of interest&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Epsilon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;427&#47;B&#46;1&#46;429&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20C&#47;S&#46;452R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GH&#47;452R&#46;V1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zeta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20B&#47;S&#46;484K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;525&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20A&#47;S484K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">G&#47;484K&#46;V3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Theta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">P&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20B&#47;S&#58;265C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Iota&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;526&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20C&#47;S&#58;484K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kappa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&#46;1&#46;617&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21A&#47;S&#58;154K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">G&#47;452R&#46;V3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2794056.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">GISAID&#58; Global initiative on sharing all influenza data&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">WHO nomenclature&#44; proposed for naming variants of concern and variants of interest&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="7" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#91;0&#44;2&#8211;8&#93;Marker</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">484E&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">E484K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">501N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N501Y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">K417N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">L452R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">E484Q&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wild type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">British B&#46;1&#46;1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&#47;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">South African B&#46;1&#46;351&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brazilian P&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Californian B&#46;1&#46;427 y B&#46;1&#46;429&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Indian B&#46;1&#46;617&#44; B&#46;1&#46;617&#46;1 and B&#46;1&#46;617&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "imagenFichero" => array:1 [
                0 => "xTab2794055.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Markers of the mutations that enable differentiating between the main variants currently circulating&#46;</p>"
        ]
      ]
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                    0 => array:2 [
                      "titulo" => "The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "I&#46;G&#46; Ovsyannikova"
                            1 => "I&#46;H&#46; Haralambieva"
                            2 => "S&#46;N&#46; Crooke"
                            3 => "G&#46;A&#46; Poland"
                            4 => "R&#46;B&#46; Kennedy"
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                    0 => array:2 [
                      "doi" => "10.1111/imr.12897"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Rev&#46;"
                        "fecha" => "2020"
                        "volumen" => "296"
                        "paginaInicial" => "205"
                        "paginaFinal" => "219"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32658335"
                            "web" => "Medline"
                          ]
                        ]
                      ]
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              "identificador" => "bib0010"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SARS-CoV-2 vaccines and the growing threat of viral variants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;P&#46; Moore"
                            1 => "P&#46;A&#46; Offit"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2021.1114"
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                        "tituloSerie" => "JAMA&#46;"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33507218"
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              "identificador" => "bib0015"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutaciones&#44; variantes y cepas de SARS-CoV-2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;J&#46; Gamero-de-Luna"
                            1 => "E&#46; Gamero-Est&#233;vez"
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                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.semerg.2021.01.001"
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                        "tituloSerie" => "Semergen&#46;"
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                        "volumen" => "47"
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                0 => array:1 [
                  "referenciaCompleta" => "PANGO Lineages&#58; Latest epidemiological lineages of SARS-CoV-2&#58; <a target="_blank" href="https://cov-lineages.org/">https&#58;&#47;&#47;cov-lineages&#46;org&#47;</a>&#46;"
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                  "referenciaCompleta" => "Nextstrain SARS-CoV-2 resources&#58; <a target="_blank" href="https://nextstrain.org/sars-cov-2">https&#58;&#47;&#47;nextstrain&#46;org&#47;sars-cov-2</a>&#46;"
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                  "referenciaCompleta" => "World Health Organization &#40;WHO&#41; Tracking SARS-CoV-2 variants &#91;Accessed 3 Jun 2021&#93;&#46;"
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              "identificador" => "bib0035"
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                  "referenciaCompleta" => "Centers for Disease Control and Prevention &#40;CDC&#41; SARS-CoV-2 Variant Classifications and Definitions &#91;Accessed 2 June 2021&#93;&#46; <a target="_blank" href="https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html">https&#58;&#47;&#47;www&#46;cdc&#46;gov&#47;coronavirus&#47;2019-ncov&#47;cases-updates&#47;variant-surveillance&#47;variant-info&#46;html</a>&#46;"
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                  "referenciaCompleta" => "European Centre for Disease Prevention and Control &#40;ECDC&#41; SARS-CoV-2 variants of concern as of 24 May 2021 &#91;Accessed 2 Jun 2021&#93;&#46;"
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                      "titulo" => "SARS-CoV-2 501Y&#46;V2 variants lack higher infectivity but do have immune escape"
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                          "etal" => true
                          "autores" => array:6 [
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                            2 => "J&#46; Wu"
                            3 => "L&#46; Zhang"
                            4 => "R&#46; Ding"
                            5 => "H&#46; Wang"
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                    0 => array:2 [
                      "doi" => "10.1016/j.cell.2021.02.042"
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