Corresponding author at: Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
was read the article
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Rodas-Martinez, Josue R. Altamirano-Yupanqui" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Alicia K." "apellidos" => "Rodas-Martinez" ] 1 => array:2 [ "nombre" => "Josue R." 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"documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Vacunas. 2022;23 Supl 2:S88-S102" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "COVID-19 vaccines: Update of the vaccines in use and under development" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S88" "paginaFinal" => "S102" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Vacunas COVID-19: actualización de las vacunas en uso y en desarrollo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 522 "Ancho" => 3356 "Tamanyo" => 92669 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">COVID-19 vaccines in use and under development.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rafaela Angotti Marta, Gisele Emy Kondo Nakamura, Bruno de Matos Aquino, Paulo R. Bignardi" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Rafaela Angotti" "apellidos" => "Marta" ] 1 => array:2 [ "nombre" => "Gisele Emy Kondo" "apellidos" => "Nakamura" ] 2 => array:2 [ "nombre" => "Bruno" "apellidos" => "de Matos Aquino" ] 3 => array:2 [ "nombre" => "Paulo R." "apellidos" => "Bignardi" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2445146022001091?idApp=UINPBA00004N" "url" => "/24451460/00000023000000S2/v3_202404040650/S2445146022001091/v3_202404040650/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Third booster vaccination and stopping the Omicron, a new variant of concern" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S103" "paginaFinal" => "S110" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Kiarash Ghazvini, Mohsen Karbalaei, Masoud Keikha" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Kiarash" "apellidos" => "Ghazvini" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "af0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 1 => array:3 [ "nombre" => "Mohsen" "apellidos" => "Karbalaei" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "af0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 2 => array:4 [ "nombre" => "Masoud" "apellidos" => "Keikha" "email" => array:1 [ 0 => "masoud.keykha90@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "af0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cr0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran" "etiqueta" => "a" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran" "etiqueta" => "b" "identificador" => "af0010" ] 2 => array:3 [ "entidad" => "Department of Microbiology and Virology, Faculty of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran" "etiqueta" => "c" "identificador" => "af0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tercera vacuna de recuerdo y freno de ómicron, una nueva variante preocupante" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1237 "Ancho" => 1772 "Tamanyo" => 161523 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">the global status vaccine coverage against the SARS-CoV-2 infection, available at: <span class="elsevierStyleInterRef" id="ir0010" href="http://www.cbrc.kaust.edu.sa/covmt/">www.cbrc.kaust.edu.sa/covmt/</span>.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">The coronavirus disease 2019 (COVID-19) is atypical pneumonia that first discovered from Wuhan China in December 2019.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> To date, there were more than 440 million reported cases as well as 5.97 million deaths throughout the worldwide (<a href="https://covid19.who.int/">https://covid19.who.int/</a>). Unfortunately, there is no effective therapeutic agents various SARS-CoV-2 variants; however, strict traveling bans, physical distancing, mask wearing, convalescent plasma therapy, and mass vaccination are still main strategy to fighting with the SARS-CoV-2 pandemics.<a class="elsevierStyleCrossRefs" href="#bb0010"><span class="elsevierStyleSup">2–5</span></a> According to the literatures, the efficacy of two coronavirus vaccination doses not complete protects against the SARS-CoV-2 omicron variants.<a class="elsevierStyleCrossRefs" href="#bb0030"><span class="elsevierStyleSup">6–8</span></a> The aim of this study was review of the literature regarding the efficacy of the third booster vaccination against Omicron variant.</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">The emergence of the VOC Omicron</span><p id="p0010" class="elsevierStylePara elsevierViewall">One and a half years have passed since the emergence of SARS-CoV-2 (severe acute respiratory syndrome Coronavirus 2), while according to WHO, more than 418 million infected cases and 5.85 million deaths have been recorded globally due to different variants of this virus.<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a> Omicron is the latest variant of concern (VOC, Pango lineage B.1.1.529, Nextstrain clade identifier 21K) that was first characterized and reported on November 2, 2021 from Botswana, South Africa (GISAID sequence accession ID: EPI_ISL_8182767).<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a> According to the GISAID database, the VOC Omicron was first characterized simultaneously in contiguous geographical areas of Botswana (hCoV-19/Botswana/R42B90_BHP_000842207/2021), Hong Kong (hCoV-19/Hong Kong/VM21045145/2021) and South Africa (hCoV-19/South Africa/CERI-KRISP-K032250/2021). The Omicron variant seems to have evolved in the African population due to the poor vaccination rates in the African population and their weakened immune system due to HIV-infection. Gao <span class="elsevierStyleItalic">et al</span>. stated that the unvaccinated African HIV-infected population has become a reservoir for the evolution, multiplication and emergence of Omicron variants.<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a> Sequence analysis of the Omicron variant showed that this variant has only 30 mutations in its spike protein and genomic substitutions have caused it to have greater doubling time, infectivity, persistence and escape from immune system than previous variants.<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Global dissemination of Omicron variant and current status</span><p id="p0015" class="elsevierStylePara elsevierViewall">Due to the dramatic surge of the Omicron variant, WHO has intensified its efforts to prioritize the global dissemination and monitoring of the novel SARS-CoV-2 variant to prevent the spread of Omicron variant. However, based on the sequences uploaded to GISAID databases, Omicron has been reported in 151 different countries (<a href="https://www.gisaid.org/hcov19-variants/">https://www.gisaid.org/hcov19-variants/</a>). As many as 511 Omicron genome sequences have been recorded till February 17, 2022, 1,362, mostly being from UK, USA, Denmark, Germany and Canada. Although many countries now have banned travel from South Africa, continuous monitoring of Nextstrain databases reflects the unbridled expansion of the VOC Omicron around the world so that it has replaced the earlier Delta variant (<a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a>).</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0020" class="elsevierStylePara elsevierViewall">Although disease severity has been shown to be lower in the Omicron than in the delta variant, ICU admission and mortality rates are increasing in most countries, especially considering that this variant is more prevalent among younger age groups.<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> To cope with the uncontrollable surge of Omicron, the U.S. Food and Drug Administration (FDA) has recently approved seven spike protein-targeted monoclonal antibodies, including Tixagevimab (COV2-2196), Cilgavimab (COV2-2130), Sotrovimab (S309), Bamlanivimab (LY-CoV555), Etesevimab (CB6), Casirivimab (REG) and Imdevimab (REGN10987) for clinical use.<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a> It has also been suggested that double-dose vaccination with BNT162b2 (Pfizer – BioNTech) and ChAdOx1 nCoV-19 (Oxford – AstraZeneca), mRNA-1273 (Moderna), and Ad26.COV2S (Johnson & Johnson) vaccines may also be useful in reducing and controlling the surge of Omicron as well as novel SARS-CoV-2. However, global vaccination coverage is poor and the need for mass vaccination intensifies with the emergence of the novel COVID-19 variant (<a class="elsevierStyleCrossRef" href="#f0010">Fig. 2</a>).</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0025" class="elsevierStylePara elsevierViewall">The rapid spread of Omicron in Western European countries with a high proportion of vaccinated population shows that the current vaccination is not a sufficient and effective strategy to stop the spread of Omicron globally. The increasing trend of Omicron re-infection in fully vaccinated individuals and inadequate neutralizing antibodies against this variant in fully vaccinated or previous natural infection by SARS-CoV-2 indicate its high ability to escape from immune system.<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> While we need new formulations of prophylactic vaccine to control Omicron, three important challenges are exacerbating global concern: 1) The emergence and evolution of new SARS-CoV-2 carrying novel mutations confer substantial resistance against vaccines. 2) Neutralizing antibodies titer waned months after administration, and 3) We need a span of 6-9 months to produce an effective vaccine against the new variant.</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Overview of Pfizer vaccine</span><p id="p0030" class="elsevierStylePara elsevierViewall">According to the literature, RNA viruses are more dangerous to human life than DNA viruses, so that the continuous mutations in RNA molecules create new variants of RNA viruses such as SARS-CoV-2.<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> Pfizer vaccine is an mRNA-based vaccine that upon injection and uptake, its S protein is expressed by local cells, and this phenomenon eventually led to the generation of immune system response; the vaccine is now available to people over the age of 16 in several countries including the United Kingdom, the United States, the European Union and Canada.<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> The effectiveness of mRNA-BNT162b2 vaccine after the second dose is 95% and it should be noted that the Pfizer vaccine can be stored for up to 10 days at -70 °C.<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a></p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Overview of Moderna vaccine</span><p id="p0035" class="elsevierStylePara elsevierViewall">The Moderna mRNA-1273 vaccine is also an mRNA-based vaccine encapsulated in nanoparticle liposome.<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> Like Pfizer vaccine, this vaccine is usable in individuals 16 years and older, as well as the effectiveness of this vaccine is 94.1% after the second dose.<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> Unlike the Pfizer vaccine, the Moderna vaccine is less sensitive to temperature changes; this vaccine requires -20 °C for shipping, and potentially is stable for 6 months in this temperature; it can be stored at 2-8 °C for 30 days.<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a></p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Overview of AstraZeneca vaccine</span><p id="p0040" class="elsevierStylePara elsevierViewall">The AZD1222 (ChAdOx1 nCoV-19) vaccine from Oxford-AstraZeneca is based on a recombinant adenovirus expressing the full-length spike protein of SARS-CoV-2 virus.<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> The interval between the first and second doses of this vaccine can be changed from four to 12 weeks, which in turn affects the flexibility of vaccination in European countries.<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> Thrombotic events are considered as the serious side effects of this vaccine, so that a cerebral venous sinus thrombosis may occur 4-16 days after vaccination.<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> AstraZeneca vaccine is authorized for active immunization to prevent COVID-19 in individuals ≥<span class="elsevierStyleHsp" style=""></span>18 years old.<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a> Considering the four-week interval between two doses, the effectiveness of this vaccine is 76% two weeks after receiving the second dose; the AstraZeneca vaccine remains stable at normal refrigerator temperatures between 2-8 °C.<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a></p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Advantages of heterologous prime-boost strategy</span><p id="p0045" class="elsevierStylePara elsevierViewall">According to the literature, the administration of a heterologous of vaccination regimen is better than homologous regimen.<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a> In a study by Barros-Martins et al., they found that a heterologous regimen of vaccination with AstraZeneca’s ChAdOx1-nCov-19 vaccine (first dose) followed by BNT162b2 vaccine (second dose) could significantly induce higher levels of cellular and humoral immunities against the Alpha (B.1.1.7), Beta (B.1.351) and Gamma (P.1) variants of concern of SARS-CoV-2 than only homologous vaccination.<a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a> In a study conducted by Schmidt et al., they observed that heterologous priming with the ChAdOx1-nCoV-19 vector vaccine followed by boosting with the mRNA vaccines (BNT162b2 or mRNA-1273) could induce a high level of immune responses e.g. spike-specific IgG, spike-specific CD4<span class="elsevierStyleHsp" style=""></span>+ T<span class="elsevierStyleHsp" style=""></span>cells, as well as neutralizing antibodies compared to homologous vector vaccine boost.<a class="elsevierStyleCrossRef" href="#bb0160"><span class="elsevierStyleSup">32</span></a> The findings of a study by Liu et al. showed that anti-spike IgG titer was higher in the ChAd/BNT schedule compared with ChAd/ChAd.<a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a> Pozzetto et al. also demonstrated that the heterologous vaccination of ChAd/BNT regimen could induce a stronger protective immunity than the homologous BNT/BNT schedule.<a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a></p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Interval between doses of COVID-19 vaccines</span><p id="p0050" class="elsevierStylePara elsevierViewall">Studies show that about AstraZeneca vaccine, a 12-week interval between two doses can be more effective in inducing the immune system compared with a 4- to 8-week interval.<a class="elsevierStyleCrossRef" href="#bb0175"><span class="elsevierStyleSup">35</span></a> On the other hand, for Moderna and Pfizer vaccines, the best time interval between two doses is at least 9 weeks, so that a 9-week interval significantly reduces hospitalization and death compared with a 3- or 4-week interval.<a class="elsevierStyleCrossRef" href="#bb0180"><span class="elsevierStyleSup">36</span></a></p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Is the third booster vaccination an effective option against SARS-CoV-2 Omicron variant?</span><p id="p0055" class="elsevierStylePara elsevierViewall">During the immune-pathogenesis of SARS-CoV-2 infection, humoral immunity blocks viral attachment and hampers entry of virus to host cell via neutralizing specific antibodies.<a class="elsevierStyleCrossRef" href="#bb0185"><span class="elsevierStyleSup">37</span></a> In addition, T cells play an important role in diminishing viral spread to other susceptible host cells by producing interferon gamma.<a class="elsevierStyleCrossRef" href="#bb0190"><span class="elsevierStyleSup">38</span></a> Neutralizing antibodies titers are typically weaned after a few months of vaccination, and Omicron mutations cause neutralizing titers to escape and confer, while mutations in immunodominant epitopes are less likely to affect T cell responses, which leads to superiority of mRNA vaccine against SARS. -CoV-2 variants.<a class="elsevierStyleCrossRef" href="#bb0195"><span class="elsevierStyleSup">39</span></a> Some recent reports have suggested that heterologous vaccination or the third dose may stimulate the immune system or cross-reactivity of neutralizing antibodies against new SARS-CoV-2 variants; thus, the potential effect of the third booster heterologous vaccination for effective immunity against the VOC Omicron has been investigated by numerous scientists. We conducted a systematic search using the ISI Web of Science, PubMed, Scopus, and Google scholar databases to retrieve all articles related to the third booster vaccination dose against SARS-CoV-2 Omicron using the keywords "Omicron", "B.1.1.529", "Vaccine", "Booster", "Neutralization" and "Antibodies". Then conclusive remarks of each study were extracted in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>.<a class="elsevierStyleCrossRefs" href="#bb0200"><span class="elsevierStyleSup">40–62</span></a></p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0060" class="elsevierStylePara elsevierViewall">Planas <span class="elsevierStyleItalic">et al</span>. (2021) revealed that Sera collected from previous COVID-19 convalescent patients had little or no neutralizing activity against Omicron, while a booster with BNT162b2 can induce the production of neutralizing antibodies against the Omicron variant.<a class="elsevierStyleCrossRef" href="#bb0315"><span class="elsevierStyleSup">63</span></a> Lee <span class="elsevierStyleItalic">et al</span>. (2022) have also recently found that heterologous vaccination with ChAdOx1 followed by BNT162b2 provides an immune response equivalent to homologous BNT162b2 vaccination.<a class="elsevierStyleCrossRef" href="#bb0320"><span class="elsevierStyleSup">64</span></a> As shown in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>, we summarized 24 eligible studies in which the mRNA-1273, BNT162b2, ADZ1222, Spikevax, Ad26.COV2S, BBIBP-CorV, and VX-CoV2373 vaccines had been used as boosters. Various studies have attempted to stimulate the immune system with heterologous or heterologous vaccination to produce an efficient neutralizing antibody titer. All included studies have reported a decreased neutralization of SARS-CoV-2 Omicron variant from 122 folds to absence of neutralization. However, the third booster vaccination induced the increased Omicron neutralization titers in most studies, but the absence of neutralization was also investigated in some studies. According to <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>, the third booster using mRNA vaccine can induce neutralizing antibodies titer more effectively. In addition, some studies have shown that booster vaccination reduces vaccine effectiveness and the incidence of Omicron (B.1.1.529) variant. It should, however, be noted that the neutralizing antibodies titer was significantly lower against the delta variant in most studies. In a recent study in the Israeli population, On <span class="elsevierStyleItalic">et al</span>. (2022) showed that the 4 dose with BNT162b2 reduces COVID-19 cases and disease severity.<a class="elsevierStyleCrossRef" href="#bb0325"><span class="elsevierStyleSup">65</span></a> Thus, a review of similar studies suggests that a third dose of vaccination can be advisable for reducing the risk of VOC Omicron breakthrough infection particularly in vulnerable populations.</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Conclusion and future perspective</span><p id="p0065" class="elsevierStylePara elsevierViewall">The VOC Omicron variant has a shorter doubling time and its mutations have caused it to spread faster and confer neutralizing antibodies, so that it has become the predominant variant in most countries/territories. Although disease severity is lower in Omicron, ICU admission and mortality rates are rising in most countries. In addition, re-infection with the Omicron variant in the fully vaccinated population has exacerbated global concern. Recent studies have shown that the third dose of vaccination leads to the cross-reactivity of antibodies and an increase in the neutralizing antibody titer. Thus, the third booster vaccination can provide better protection in vulnerable populations e.g. immunocompromised individuals. Based on studies, while administration of a third dose of vaccine can be benefit in some immunocompromised patients such as recipients of solid-organ transplants or hemodialysis patients, a partial response of immune system to SARS-CoV-2 is seen in patients with B cell lymphoproliferative disease.<a class="elsevierStyleCrossRef" href="#bb0330"><span class="elsevierStyleSup">66</span></a> According to randomized clinical trial studies, administration of monoclonal antibodies significantly reduces (70-80%) hospitalizations and mortality in immunosuppressed patients.<a class="elsevierStyleCrossRef" href="#bb0335"><span class="elsevierStyleSup">67</span></a> Recent studies have shown that the third booster was safe and well tolerated. The booster administration after the double-dose vaccination is an advisable strategy to reduce the risk of infection and spread of the Omicron variant. However, the efficacy of the third booster vaccination in fully vaccinated subjects has not been confirmed yet, nor has the role of heterologous or homologous vaccination in increasing neutralizing antibodies against Omicron been determined yet. We have no complete detailed information on the vaccine type, booster dosing, optimal dosing intervals and vaccination timeline yet. The third booster vaccination particularly in vulnerable subjects as well as the world mass vaccination to efficient vaccine production can be a critical step in regressing the surge of the new SARS-CoV-2 variant and controlling the Omicron pandemic.</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Conflict of interest statement</span><p id="p0070" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres2117962" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "as0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1804121" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2117961" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "as0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1804122" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "s0010" "titulo" => "The emergence of the VOC Omicron" ] 6 => array:2 [ "identificador" => "s0015" "titulo" => "Global dissemination of Omicron variant and current status" ] 7 => array:2 [ "identificador" => "s0020" "titulo" => "Overview of Pfizer vaccine" ] 8 => array:2 [ "identificador" => "s0025" "titulo" => "Overview of Moderna vaccine" ] 9 => array:2 [ "identificador" => "s0030" "titulo" => "Overview of AstraZeneca vaccine" ] 10 => array:2 [ "identificador" => "s0035" "titulo" => "Advantages of heterologous prime-boost strategy" ] 11 => array:2 [ "identificador" => "s0040" "titulo" => "Interval between doses of COVID-19 vaccines" ] 12 => array:2 [ "identificador" => "s0045" "titulo" => "Is the third booster vaccination an effective option against SARS-CoV-2 Omicron variant?" ] 13 => array:2 [ "identificador" => "s0050" "titulo" => "Conclusion and future perspective" ] 14 => array:2 [ "identificador" => "s0055" "titulo" => "Conflict of interest statement" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-02-24" "fechaAceptado" => "2022-05-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1804121" "palabras" => array:4 [ 0 => "SARS-CoV-2" 1 => "COVID-19" 2 => "Omicron" 3 => "Vaccine" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1804122" "palabras" => array:4 [ 0 => "SARS-CoV-2" 1 => "COVID-19" 2 => "Ómicron" 3 => "Vacuna" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">The SARS-CoV-2 omicron variant is recent member of variant of concerns that confer neutralizing antibodies and escape immune system due to harboring more than 40 mutations. Current evidences suggest two dosages SARS-CoV-2 vaccine dose not efficient protects against new variants of SARS-CoV-2; however, recent studies declare that the third booster vaccination can elicit higher antibodies concentration as well as cross-reaction between neutralizing antibodies and new SARS-CoV-2 variants. On the other hand, although a third booster vaccination seems to be benefit in some immunocompromised patients such as recipients of solid-organ transplants or hemodialysis patients, but in other immunosuppressed patients, for instance patients with B cell lymphoproliferative disease partially respond to SARS-CoV-2. Herein, we evaluate the effectiveness of the third booster vaccination against Omicron variant using comprehensive literature review.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="as0010" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">La variante ómicron de SARS-CoV-2 es un miembro reciente de variantes preocupantes, que confiere anticuerpos neutralizantes y escapa al sistema inmune debido a que alberga más de 40 mutaciones. Las evidencias actuales sugieren que dos dosis de la vacuna contra la SARS-CoV-2 no protegen eficientemente frente a las nuevas variantes de SARS-CoV-2. Sin embargo, los estudios recientes afirman que la tercera vacuna de refuerzo puede suscitar una mayor concentración de anticuerpos, así como una reacción cruzada entre los anticuerpos neutralizantes y las nuevas variantes de SARS-CoV-2. Por otro lado, aunque la tercera vacuna de refuerzo parece ser beneficiosa para algunos pacientes inmunocomprometidos, tales como los receptores de trasplantes de órganos sólidos, o los pacientes de hemodiálisis, otros pacientes inmunosuprimidos, como por ejemplo los pacientes con enfermedad linfoproliferativa de células B, responden parcialmente a la SARS-CoV-2. Por tanto, evaluamos la efectividad de la tercera vacuna de refuerzo frente a la variante ómicron, utilizando una revisión amplia de la literatura.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="np0005">Represents co-first author</p>" "identificador" => "fn0005" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1815 "Ancho" => 2031 "Tamanyo" => 342993 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">the rising trend of the VOC omicron (B.1.1.529) throughout the worldwide, available at: <span class="elsevierStyleInterRef" id="ir0005" href="https://www.gisaid.org/hcov19-variants/">https://www.gisaid.org/hcov19-variants/</span>.</p>" ] ] 1 => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1237 "Ancho" => 1772 "Tamanyo" => 161523 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">the global status vaccine coverage against the SARS-CoV-2 infection, available at: <span class="elsevierStyleInterRef" id="ir0010" href="http://www.cbrc.kaust.edu.sa/covmt/">www.cbrc.kaust.edu.sa/covmt/</span>.</p>" ] ] 2 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">First author \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">vaccine type \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reduced Omicron neutralization (folds)/primary VE% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Booster vaccination type \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Increased Omicronneutralization after booster (folds)/second VE% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Omicron infection rate with two vs. three booster \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ref \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Beltran et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273, BNT162b, and Ad26.COV2.S \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 fold for mRNA-1273, 12 fold for BNT162b, and 17 fold for Ad26.COV2.S \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273, and BNT162b \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 fold for mRNA-1273 and 27 fold for BNT162b \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0200"><span class="elsevierStyleSup">40</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dejnirattisai et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADZ1222, and BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.7 fold for ADZ1222 and 14.2 fold for BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADZ1222, and BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.7-fold for ADZ1222 and 34.2 fold for BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0205"><span class="elsevierStyleSup">41</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Edara et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273, and BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No detectable titer \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273, and BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.4 fold for mRNA-1273 and 14 fold for BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0210"><span class="elsevierStyleSup">42</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hoffmann et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0215"><span class="elsevierStyleSup">43</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Andrews et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2, and ChAdOx1 dose \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88.0% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.5% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">44</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hansen et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2, and mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55.2% for BNT162b2 and 36.7% for mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.6% BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0225"><span class="elsevierStyleSup">45</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Muik et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.8 fold for BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.4 fold for BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0230"><span class="elsevierStyleSup">46</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Then et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CoronaVac \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.3 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.4 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0235"><span class="elsevierStyleSup">47</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tada et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 and mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6-8 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0240"><span class="elsevierStyleSup">48</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zeng et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21.3-fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.1 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0245"><span class="elsevierStyleSup">49</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Willett et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2, ChAdOx1 or mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 fold for BNT162b2, 14 fold for ChAdOx1 and 74 fold for mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 or mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not significant \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0250"><span class="elsevierStyleSup">50</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zuo et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2, mRNA-127 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2, mRNA-127 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.3 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0255"><span class="elsevierStyleSup">51</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leung et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0260"><span class="elsevierStyleSup">52</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chaguza et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ad26.COV2.S \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273 or BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7% to 2.2% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0265"><span class="elsevierStyleSup">53</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kislaya et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cominarty, Spikevax, Vaxzevria and Janssen COVID-19 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cominarty andSpikevax \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.1; CI 95% :1.8 to 2.4 vs. OR<span class="elsevierStyleHsp" style=""></span>= 5.2; CI 95%: 3.1 to 8.8 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0270"><span class="elsevierStyleSup">54</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chemaitelly et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 and mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61.9% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 and mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55% \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0275"><span class="elsevierStyleSup">55</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tan et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ad26.COV2.S or BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0280"><span class="elsevierStyleSup">56</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Accorsi et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 or mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 or mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.34; CI 95%: 0.32-0.36 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0285"><span class="elsevierStyleSup">57</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rose et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.9 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mRNA-1273 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.6 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0290"><span class="elsevierStyleSup">58</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Then et al., 2022 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CoronaVac \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.1 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.4 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0295"><span class="elsevierStyleSup">59</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ai et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BBIBP-CorV \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.9 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BBIBP-CorV after 28 days \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.6 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0300"><span class="elsevierStyleSup">60</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Schmidt et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">127 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BNT162b2 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42.1 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0305"><span class="elsevierStyleSup">61</span></a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mallory et al., 2021 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NVX-CoV2373 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.2 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VX-CoV2373 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.8 fold \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NA \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bb0310"><span class="elsevierStyleSup">62</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3501808.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Characteristics of included studies.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:67 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lancet COVID-19 Commission Statement on the occasion of the 75th session of the UN General Assembly" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.D. Sachs" 1 => "S.A. Karim" 2 => "L. Aknin" 3 => "J. Allen" 4 => "K. Brosbøl" 5 => "G.C. Barron" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(20)31927-9" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2020" "volumen" => "396" "numero" => "10257" "paginaInicial" => "1102" "paginaFinal" => "1124" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32941825" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "What are the clinical benefits of tocilizumab for COVID-19 patients? 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