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Editorial
Autumn 2023 SARS-CoV-2 immunization: Who should be vaccinated and how?
Vacunación frente al SARS-CoV-2 en otoño de 2023: ¿a quién y cómo hay que vacunar?
Fernando Moraga-Llopa,b,
Corresponding author
fernandomoragallop@gmail.com

Corresponding author.
, Magda Campins-Martíc
a Societat Catalana de Pediatria, Barcelona, Spain
b Asociación Española de Vacunología, Barcelona, Spain
c Facultad de Medicina, Universidad Autónoma de Barcelona, Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0005" class="elsevierStylePara elsevierViewall">Although it is no longer a public health emergency of international concern&#44; the COVID-19 pandemic is not yet over and we must continue epidemiological surveillance and vaccination&#44; based on the current status of the infection&#46; The emergency was declared by the World Health Organisation &#40;WHO&#41; on 30 January 2020&#44; and ended on 5 May 2023&#44; after 3&#8239;years and 3&#8239;months&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> In Spain&#44; the end of the health crisis caused by COVID-19 was declared on 4 July 2023 &#40;BOE of 5 July 2023&#41;&#46;</p><p id="p0010" class="elsevierStylePara elsevierViewall">SARS-CoV-2 has remained endemic among us&#44; but does not&#44; for the moment&#44; show a seasonal pattern of spread similar to that of influenza&#46; In Spain&#44; the months with the highest mortality due to COVID-19 after the first wave of the onset of the pandemic in 2020&#44; were January and February 2021 and January and July 2022&#46;<a class="elsevierStyleCrossRefs" href="#bb0010"><span class="elsevierStyleSup">2&#8211;4</span></a> Therefore&#44; seasonal behaviour is not defined and the circulation of new&#44; much more transmissible variants&#44; such as omicron and its subvariants&#44; holiday movements&#44; and the relaxation of non-pharmacological protective measures are factors to be taken into account&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">The decreasing trend in the number of deaths&#44; hospitalisations and admissions to intensive care units &#40;ICU&#41;&#44; and the high levels of population immunity&#44; especially vaccine and hybrid immunity&#44; were the determining factors in the WHO&#39;s declaration of the end of the health emergency&#46; Nevertheless&#44; COVID-19 remains a health and social problem&#44; and the risks and uncertainties about its evolution are still a threat to global health&#46; The WHO declaration is accompanied by temporary recommendations for all member states&#44; including the integration of vaccination against COVID-19 into the lifelong vaccination programme&#44; especially in high-risk individuals&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">It is estimated that 14 billion doses of vaccine administered worldwide have prevented more than 20 million deaths from COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> However&#44; the virus continues to circulate and will continue to cause ICU admissions and deaths&#44; and millions of patients will continue to live with the sequelae of persistent long COVID-19&#46; In Spain&#44; life expectancy has been reduced by 1&#46;5&#8239;years&#44; and across the WHO European region 36 million people may have developed clinical symptoms of long COVID-19 during the first 3&#8239;years of the pandemic&#46;<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">In Spain&#44; hospitalisations due to COVID-19 during 2020 and 2021 were 498&#8239;789&#44; 10&#46;9&#37; in ICUs&#44; and the case fatality rate was 14&#46;3&#37; in admitted patients &#40;71&#8239;437 people&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> In 2022&#44; although confirmed COVID-19 mortality was 20&#37; lower than in 2021&#44; it represented for the third consecutive year the leading cause of death&#44; with 31&#8239;559 deaths&#44; corresponding to 6&#46;8&#37; of the total&#44; followed by ischaemic heart disease&#44; with 28&#8239;687 deaths&#44; and in third place by cerebrovascular disease&#44; with 24&#8239;558 deaths&#46;<a class="elsevierStyleCrossRefs" href="#bb0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="p0030" class="elsevierStylePara elsevierViewall">In this new post-emergency phase&#44; vaccination&#44; together with non-pharmacological measures&#44; remains the most effective preventive measure as outlined in the WHO statement<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> and needs to be integrated into the life-long immunization programme&#46; Efforts should be maintained to increase vaccination coverage in individuals in high-risk groups with the recommended vaccines and to continue to actively address uptake and demand issues with communities&#46; To this end&#44; a document has been published in Spain&#44; <span class="elsevierStyleItalic">Recommendations for vaccination against influenza and COVID-19 in the 2023&#8211;2024 season in Spain&#44;</span> approved by the Public Health Commission on 12 July 2023&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a></p><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0005">Who should be vaccinated&#63;</span><p id="p0035" class="elsevierStylePara elsevierViewall">Given the current epidemiological situation&#44; the vaccination strategy in autumn 2023 should include&#44; first and foremost&#44; the groups at greatest risk by age&#44; i&#46;e&#46; people aged 60&#8239;years and older&#46; Mortality from COVID-19 in Spain in 2022 was concentrated in the elderly&#58; 95&#46;9&#37; were aged 60&#8239;years and older &#40;70&#46;8&#37; aged 80&#8239;years and older&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bb0010"><span class="elsevierStyleSup">2&#8211;4</span></a> In the period 2020&#8211;2021&#44; hospitalisations in those aged 64&#8239;years and older &#40;267&#8239;110 cases&#41; accounted for 53&#46;5&#37; of all admissions and 44&#46;9&#37; of those requiring ICU admission&#59; furthermore&#44; case fatality was highest in patients admitted to ICUs aged 74&#8239;years and older &#40;27&#46;1&#37; in 2020 and 31&#37; in 2021&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a></p><p id="p0040" class="elsevierStylePara elsevierViewall">In second place are people from the age of 6&#8239;months with some type of immunocompromise&#44; including severe immunosuppression and inborn immunity impairment&#44; and also those suffering from chronic diseases&#44; especially those affecting the vascular endothelium&#44; such as diabetes and cardiovascular diseases&#44; with a list of more than 20 risk conditions&#44; according to the document approved by the Public Health Commission&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">Thirdly&#44; the vaccination strategy should cover people living and working in nursing homes&#44; homes for the disabled and the chronically ill and institutionalised&#59; pregnant women in any trimester of pregnancy&#59; health and social care staff&#59; and all contacts of patients belonging to at-risk groups&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a></p><p id="p0050" class="elsevierStylePara elsevierViewall">Furthermore&#44; vaccination should be available to all persons who request it&#44; even if they do not belong to the groups in which vaccination is recommended&#44; provided that at least 5&#8239;months have elapsed since a previous dose of vaccine was administered or infection has occurred&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Which vaccines should be administered&#63;</span><p id="p0055" class="elsevierStylePara elsevierViewall">In September 2022&#44; the European Medicines Agency &#40;EMA&#41; approved the first adapted or modified vaccines&#44; which are part of the second-generation group of vaccines and are messenger RNA vaccines&#58; Comirnaty Original&#47;Omicron BA&#46;1 &#40;Pfizer&#47;BioNTech&#41;&#44; Comirnaty Original&#47;Omicron BA&#46;4&#8211;5 &#40;Pfizer&#47;BioNTech&#41;&#44; Spikevax bivalent Original&#47;Omicron BA&#46;1 &#40;Moderna&#41;&#44; and Spikexax bivalent&#47;Omicron BA&#46;4&#8211;5 &#40;Moderna&#41;&#46; A new group of vaccines&#44; recombinant protein vaccines&#44; has also been added&#58; Nuvaxovid &#40;Novavax&#41;&#44; VidPrevtiyn Beta &#40;Sanofi&#47;GSK&#41;&#44; and Bimervax &#40;HIPRA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0060" class="elsevierStylePara elsevierViewall">These second-generation vaccines have shown additional protection&#44; compared to vaccines made with the original strain&#44; against hospitalisation&#44; severe forms of the disease and death from COVID-19 caused by omicron subvariants&#46;<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">Worldwide&#44; since the beginning of 2023&#44; more than 90&#37; of SARS-CoV-2 infections have been caused by XBB-descendant sub-lineages &#40;data as of 29 July 2023&#44; GISAID&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> Omicron XBB is the sublineage with the highest immune escape to date&#59; relative to Omicron BA&#46;5&#44; the subvariants XBB&#46;1&#46;5 and XBB&#46;1&#46;16 have 20 and 23 mutations&#44; respectively&#44; which justifies updating the composition of the vaccines&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a></p><p id="p0070" class="elsevierStylePara elsevierViewall">The need for new preparations responds to the decreasing effectiveness of available vaccines due to the progressive loss of immunity over time &#40;waning immunity&#41;&#44; due to the emergence of variants with increased vaccine escape&#44; i&#46;e&#46; evading neutralising antibodies&#44; especially against infection and mild disease&#46;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> The administration of a booster dose of adapted BA&#46;4&#8211;5 vaccines increases the neutralising antibody titre and cellular immunity against XBB&#44; but with much lower titres than those achieved against the previous subvariants&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> The safety and reactogenicity profiles of the booster doses are similar to those of primovaccination&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">In May and June 2023&#44; recommendations for new vaccines for the coming autumn were communicated by various agencies&#46;</p><p id="p0080" class="elsevierStylePara elsevierViewall">On 8 May&#44; the International Coalition of Medicines Regulatory Authorities &#40;ICMRA&#41;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> discussed the future of SARS-CoV-2 vaccination and especially the composition of vaccines for the coming autumn&#46; The representative of the US Food and Drug Administration &#40;FDA&#41; reported that the spike protein of XBB&#46;1&#46;5 is similar to that of XBB&#46;1&#46;16 &#40;only a difference of 2 mutations in the receptor binding domain &#91;RBD&#93; and in the N-terminal domain of the protein &#91;NTD&#93;&#41; and to that of XBB&#46;1&#46;9&#46; For their part&#44; the EMA representative at ICMRA stated that the evidence presented supports the value of having monovalent vaccines tailored to the circulating variants&#44; and that pending further data&#44; they should contain XBB&#44; although not all approved platforms in the EU will be available by next autumn&#46;</p><p id="p0085" class="elsevierStylePara elsevierViewall">The WHO Technical Advisory Group &#40;TAG-CO-VAC&#41;&#44; in a report dated 18 May&#44;<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> also issued recommendations on the composition of future vaccines&#46; Noting that current vaccines remain highly protective against severe disease and death&#44; and that protection against symptomatic disease is limited and less durable&#44; it recommends upgrading to XBB&#46;1 lineages&#44; such as XBB&#46;1&#46;5 or XBB&#46;1&#46;16 in monovalent formulation&#46; These vaccines may be administered as primary or booster vaccination&#46; This recommendation is based on the following considerations&#58; &#40;a&#41; the ancestral virus and its closest derivatives are no longer circulating&#44; &#40;b&#41; the vaccine antigens of the ancestral virus induce undetectable or very low titres of antibodies against currently circulating SARS-CoV-2 variants&#44; and &#40;c&#41; the inclusion in bivalent vaccines of the ancestral virus reduces the immune response to the new antigens compared to monovalent vaccines &#40;a phenomenon known as immune imprinting or &#8220;original antigenic sin&#8221;&#41;&#46; This explains the progressive decline in the effectiveness of current bivalent vaccines as new variants of SARS-CoV-2 emerge&#46;</p><p id="p0090" class="elsevierStylePara elsevierViewall">The EMA and the European Centre for Disease Prevention and Control &#40;ECDC&#41; have published a joint statement&#44; dated 6 June 2023&#44; on the update of adapted COVID-19 vaccines and considerations for use in autumn this year&#46;<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> A monovalent XBB&#46;1&#46;5 vaccine is recommended to provide protection against current dominant and emerging strains&#44; or other formulations that achieve an immune response against this subvariant&#46; The following simplified vaccination schedule is proposed&#44; although the recommendations of national health authorities should always be followed&#58; &#40;a&#41; persons over 5&#8239;years of age&#44; 1 dose of the matched monovalent vaccine&#44; &#40;b&#41; children under 5&#8239;years of age with no history of vaccination or previous SARS-CoV-2 infection&#44; a primary series consisting of 2 or 3 doses&#44; depending on the matched monovalent vaccine administered &#40;as with first generation vaccines&#41;&#44;<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> and &#40;c&#41; persons with immunosuppression&#44; administer additional doses according to national recommendations&#46; For revaccinations&#44; a minimum interval of 3&#8211;4&#8239;months since the last dose or since the onset of infection should be expected&#46;</p><p id="p0095" class="elsevierStylePara elsevierViewall">The FDA&#39;s Vaccines Related Biological Products Advisory Committee &#40;VRBPAC&#41; at its meeting on 15 June 2023&#44;<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> selected the omicron subvariant XBB&#46;1&#46;5 &#40;whose structural characteristics are quite similar to those of others currently circulating&#44; such as XBB&#46;1&#46;16 and XBB&#46;2&#46;3&#41; as a unique vaccine candidate for use in the autumn of this year&#46; The following is a summary of the data on the investigational vaccines presented at this meeting by Moderna&#44; Pfizer&#44; and Novavax&#46; The other 2 recombinant protein vaccines available in Spain &#40;Sanofi&#47;GSK and HIPRA&#41; will not present any adapted vaccine for the 2023&#8211;2024 season and will remain the originals&#46;</p><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Monovalent messenger RNA vaccine XBB&#46;1&#46;5 adapted from Moderna &#40;Spikevax&#44; designation of the original&#41;</span><p id="p0100" class="elsevierStylePara elsevierViewall">Immunogenicity studies conducted to test the neutralising capacity of antibodies generated by a booster dose of bivalent Original &#40;Wuhan&#41;&#47;Omicron BA&#46;4&#8211;5 vaccine in individuals with or without previous infection showed very low titres against XBB&#46;1&#46;5 &#40;geometric mean neutralising antibody titres &#91;GMT&#93; of 556 and 298&#44; respectively&#41;&#46; Preclinical studies with monovalent matched XBB&#46;1&#46;5 vaccine used as primary series show very high induction of neutralising antibody titres &#40;GMT of 16&#8239;672 versus XBB&#46;1&#46;5 and 20&#8239;915 versus XBB&#46;1&#46;16&#41;&#46; A Phase 2&#47;3 immunogenicity and safety clinical trial of the monovalent XBB&#46;1&#46;5 vaccine &#40;third booster&#41; in adults aged 18&#8239;years and older who had received 4 doses of mRNA vaccine showed a greater than 16-fold increase in neutralising antibody titre over the pre-booster value against XBB&#46;1&#46;5 and a 10-fold increase against XBB&#46;1&#46;16 &#40;GMT of 2579 and 2263&#44; respectively&#41;&#46; The safety profile was similar to that observed with already licenced vaccines&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a></p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Monovalent messenger RNA vaccine XBB&#46;1&#46;5 adapted from Pfizer &#40;Comirnaty&#44; designation of original&#41;</span><p id="p0105" class="elsevierStylePara elsevierViewall">Based on data from clinical trials with the bivalent Original &#40;Wuhan&#41;&#47;Omicron BA&#46;4&#8211;5 and the monovalent Original vaccine administered as a fourth dose in persons with or without previous infection&#44; the neutralising antibody titres induced by both vaccines against the Omicron subvariants XBB&#46;1&#46;5 and XBB&#46;1&#46;16 were lower &#40;GMT of 111 and 93&#44; respectively&#41; than those against BA&#46;4&#8211;5 &#40;GMT between 1076 and 1197&#41;&#46; In contrast&#44; results from preclinical studies show that a booster dose with the adapted monovalent vaccine XBB&#46;1&#46;5 induces a high neutralising response against the sub-lines XBB&#46;1&#46;5&#44; XBB&#46;1&#46;16&#44; and XBB&#46;2&#46;3 &#40;GMT of 1800&#44; 3766&#44; and 3020&#44; respectively&#41;&#46; Similar results have been obtained with this vaccine used as a primary vaccination&#46; The safety profile was also similar to that observed with already licenced vaccines&#46;<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Monovalent XBB&#46;1&#46;5 adjuvanted recombinant protein vaccine adapted from Novavax &#40;Nuvaxovid&#44; designation of original&#41;</span><p id="p0110" class="elsevierStylePara elsevierViewall">Preclinical studies in mice primovaccinated with 2 doses of monovalent XBB&#46;1&#46;5 vaccine show high titres of neutralising antibodies to the XBB&#46;1&#46;5 and XBB&#46;1&#46;16 subvariants &#40;GMT of 4554 and 4156&#44; respectively&#41;&#46; Studies in mice primed with bivalent vaccine &#40;Original&#47;Omicron BA&#46;5&#41; and given a dose of monovalent XBB&#46;1&#46;5 showed similar results &#40;GMT of 5816 and 8413&#44; respectively&#41;&#46; Concordant data have been observed in preclinical studies in macaques&#46; Induction of cell-mediated immune responses against the XBB26 variant has also been demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a></p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">HIPRA vaccine</span><p id="p0115" class="elsevierStylePara elsevierViewall">The current vaccine is bivalent&#44; with a Beta-Alpha dimer&#44; and adjuvanted &#40;Bimervax&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> An adapted form&#44; a monovalent dimer of an omicron XBB subvariant&#44; is under development and the clinical trial is scheduled to start in November 2023 &#40;source&#58; HIPRA&#41;&#46; Based on preliminary data from 2 sub-cohorts of individuals participating in the initial Bimervax clinical trial &#40;1 receiving 3 prior doses of Comirnaty mRNA vaccine and the other 2 doses of Comirnaty mRNA and 1 dose of Bimervax&#41;&#44; administration of a fourth dose induced neutralising antibody titres to XBB&#46;1&#46;5 at 14&#8239;days &#40;GMT between 257 and 307&#44; respectively&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a></p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Sanofi&#47;GSK vaccine</span><p id="p0120" class="elsevierStylePara elsevierViewall">The current vaccine &#40;VidPrevtiyn Beta&#41; will not be available in an adapted form for the time being&#46; There is some preliminary immunogenicity data for this vaccine against XBB&#44; but it is not published &#40;source&#58; Sanofi&#41;&#46;</p></span></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Conclusions</span><p id="p0125" class="elsevierStylePara elsevierViewall">Recommendations regarding which persons should be vaccinated with which vaccines will have to be modified according to the epidemiological evolution of the pandemic &#40;emergence of new variants&#44; according to transmissibility&#44; and degree of vaccine escape&#41; and the availability of new vaccines &#40;mucosal&#44; broad-spectrum&#44; or other&#41;&#46; In addition&#44; epidemiological surveillance and monitoring of vaccine safety and effectiveness&#44; as well as vaccination coverage&#44; should continue&#46; COVID-19&#44; for the moment&#44; is not a seasonal disease like influenza&#44; as SARS-CoV-2 is behaving very differently and time will tell&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">On the same day as this article was being finalised&#44; a WHO communiqu&#233; was published&#44; dated 9 August 2023&#44; indicating that several variants of interest &#40;VOIs&#41; are currently being analysed&#44; including EG&#46;5 &#40;also called Eris&#41;&#44; an omicron variant lineage descended from XBB&#46;1&#46;9&#46;2 and XBB&#46;1&#46;5&#44; with a subvariant EG&#46;5&#46;1 accounting for 88&#37; of the sequences available for EG&#46;5&#46; This new variant is already present in more than 50 countries&#44; its incidence is increasing and has led to an increase in the number of infections&#46; Its most relevant characteristics are greater transmissibility and more immune escape than XBB&#44; although it does not seem to be associated with greater severity&#46;<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a></p><p id="p0135" class="elsevierStylePara elsevierViewall">Therefore&#44; as we have already pointed out several times&#44; epidemiological surveillance &#40;diagnostic tests&#44; case reporting&#44; and virus sequencing&#41; must continue and the WHO Director-General has reminded us that &#8220;the risk remains that a more dangerous variant could emerge that could cause a sudden increase in cases and deaths&#8221;&#46;</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Funding</span><p id="p0140" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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ISSN: 24451460
Original language: English
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es en pt

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Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos