Letter to the Editor
Suboptimal humoral immunological response to the 2nd dose of anti-COVID19 mRNA-1273 vaccine (Moderna) in kidney transplant patients
Respuesta inmunológica humoral insuficiente a la 2.a dosis de vacuna anti-COVID19 mRNA-1273 (Moderna) en pacientes portadores de trasplante renal
Jesús Martín-García
, Gilda Carreño Cornejo, Rosario Manzanedo Bueno, Consolación Rosado Rubio, David Menéndez González, Dolores Barreda Grande, Carmen Felipe Fernández
Corresponding author
Sección de Nefrología, Complejo asistencial de Ávila, Ávila, Spain
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] ] ] 1 => array:2 [ "nombre" => "Gilda" "apellidos" => "Carreño Cornejo" ] 2 => array:2 [ "nombre" => "Rosario" "apellidos" => "Manzanedo Bueno" ] 3 => array:2 [ "nombre" => "Consolación" "apellidos" => "Rosado Rubio" ] 4 => array:2 [ "nombre" => "David" "apellidos" => "Menéndez González" ] 5 => array:2 [ "nombre" => "Dolores" "apellidos" => "Barreda Grande" ] 6 => array:2 [ "nombre" => "Carmen" "apellidos" => "Felipe Fernández" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sección de Nefrología, Complejo asistencial de Ávila, Ávila, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Respuesta inmunológica humoral insuficiente a la 2.<span class="elsevierStyleSup">a</span> dosis de vacuna anti-COVID19 mRNA-1273 (Moderna) en pacientes portadores de trasplante renal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1880 "Ancho" => 2497 "Tamanyo" => 156263 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Titres of anti-Spike SARS-CoV-2 antibodies of patients and controls 8 weeks after the 2nd dose of mRNA-1273 (Moderna) vaccine. Mean and 95% CI.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Since the start of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), various groups of researchers have found a weak immune response in patients with solid organ transplants.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> This finding and the fact that some transplant patients have suffered from COVID-19 after being fully vaccinated with two doses, has led to the recommendation, in some countries, of a third dose of vaccine in these patients.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We prospectively studied the humoural response to the mRNA-1273 (Moderna) vaccine in 73 kidney transplant recipients by quantitatively determining anti-Spike IgG antibodies to SARS-CoV-2, immediately before the second dose and eight weeks after vaccine administration, analysed by microparticle chemiluminescence (Abbott Alinity system [ref. value + >50 AU/ml]). The results were compared with the response to the same mRNA-1273 vaccine administered to 30 patients on haemodialysis (HD), 12 on peritoneal dialysis (PD), 21 pre-dialysis (pre-D) and 47 controls, who were healthy hospital workers.</p><p id="par0015" class="elsevierStylePara elsevierViewall">As this was a prospective study, it was approved by the Independent Ethics Committee for Clinical Trials with medicines (IECm) of the institution, Gerencia de Asistencia Sanitaria de Ávila [Ávila Healthcare Management].</p><p id="par0020" class="elsevierStylePara elsevierViewall">The mean age of the transplant recipients was 60.12 ± 10.4 and the time since transplantation was 123–11,888 days; 56.1% were male. Four patients who had previous SARS-CoV-2 infection and three patients who had been in close contact and had a high suspicion of infection had very high titres (40,374.6 ± 55,211.5 AU/ml) and were excluded from the analysis. The response to the first dose of the vaccine, defined by IgG levels >50 AU/ml, was only found in 16.4% (11 patients) with a mean anti-Spike IgG antibody (Ab) titre of 270.8 ± 322.0 (median: 172.9; r = 52.6–19,650.3); 79.8% had levels below 50 AU/ml, and 21 (28.7%) were anergic (0–<1 AU/ml). Eight patients on HD, one on PD and two pre-D had already had clinical SARS-CoV-2 infection and all developed a strong anti-Spike Ab response to the first dose of vaccine (patients on HD: 42,181 ± 22,798; PD: 35,418.4 AU/ml; pre-D: 36,934.3 ± 35,026.7). Of the rest, 90.9% of patients on HD, 72.7% of those on PD and 78.9% of the pre-D developed an Ab response >50 AU/ml, with mean figures of 377.5 ± 350.4 AU/ml (median: 314.9) in HD; 1176.5 ± 1823.8 (median: 646.7) in PD and 1158.3 ± 1431.1 (median: 683.6) in pre-D, with significant differences compared to the transplant recipients (p = 0.004). The transplant recipients with IgG anti-Spike <50 AU/ml were older, 63.7 ± 9 vs 58.5 ± 10 (p = 0.1), with more lymphopenia 1568 ± 731 vs 2060 ± 680 (p = 0.05); and there was a correlation between IgG anti-Spike and lymphocytes: R = 0.32 (p = 0.007); a certain negative correlation was also detected with tacrolimus, R = −0.24, and prednisone, R = −0.14, although not statistically significant (p = 0.1). Eight weeks after the second dose of mRNA-1273, another antibody determination was performed; 35 transplant recipients already had levels >50 AU/ml, (53.03% vs 100% of patients on HD, PD, pre-D and healthy controls) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The anti-Spike Ab titre was also lower than the rest of the groups: mean 1544.11 ± 4279.58 AU/ml (95% CI: 2576.58–511.6) vs 4000.3 ± 5567.2 (95% CI: 6683.62–1317.03) on HD; 3709.3 ± 2889.6 (95% CI: 5650.61–1768.03) on PD; 7288.4 ± 7849.1 (95% CI: 12,031.6–2545.2) in pre-D; and significantly lower than those of healthy controls: mean 16,226.3 ± 11,319.8 (95% CI: 19,462.5–2545.2) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). There was no evidence of any serious events after the first or second doses, or any rejection phenomenon or variation in serum creatinine. In the follow-up period, none of the patients or controls developed COVID-19 infection, despite having a low antibody titre, perhaps related to a certain degree of cellular immunity.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">This study shows that, in transplant recipients, the immunisation achieved with the second dose of mRNA-1273 (Moderna) vaccine improves considerably, but without reaching a prevalence of at least 70% in this population, with anti-Spike anti-IgG Ab titres significantly lower than the controls and the rest of the groups of patients with advanced chronic kidney disease (ACKD). As a large proportion of transplant recipients remain at risk of COVID-19, another third dose of vaccine should be provided as soon as possible, as is already being done in other countries.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1338 "Ancho" => 2380 "Tamanyo" => 129987 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Percentage of patients and controls who had developed anti-Spike SARS-CoV-2 Ab, at a titre above 50 AU/ml, at eight weeks after administration of the second dose of mRNA-1273 (Moderna) vaccine.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1880 "Ancho" => 2497 "Tamanyo" => 156263 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Titres of anti-Spike SARS-CoV-2 antibodies of patients and controls 8 weeks after the 2nd dose of mRNA-1273 (Moderna) vaccine. Mean and 95% CI.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.J. Boyarsky" 1 => "W.A. Werbel" 2 => "R.K. Avery" 3 => "A.A.R. Tobian" 4 => "A. Massie" 5 => "D.L. 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Izopet" 4 => "A. del Bello" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMc2108861" "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "2021" "volumen" => "38" "paginaInicial" => "661" "paginaFinal" => "662" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000004300000003/v1_202309041339/S2013251423001190/v1_202309041339/en/main.assets" "Apartado" => array:4 [ "identificador" => "35436" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000004300000003/v1_202309041339/S2013251423001190/v1_202309041339/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251423001190?idApp=UINPBA000064" ]
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