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Humoral Response to Third Dose of SARS-CoV-2 Vaccines in the CKD Spectrum

2022; Lippincott Williams & Wilkins; Volume: 17; Issue: 6 Linguagem: Inglês

10.2215/cjn.01770222

1555-905X

Borja Quiroga, María José Soler, Alberto Ortíz, Esther Orero, Sandra Tejedor, Carlos Jesús Jarava Mantecón, Virginia Olinda Gómez Pérez, Antonio Franco, Ana Sánchez Horrillo, Marta Carretero, Maria Teresa Jaldo Rodríguez, Manuel Antonio Carnerero Di Riso, Shaira Martínez, Carmen Calderón González, Michal Červienka, Nicolás Macías Carmona, David Arroyo, Katia M. Pérez del Valle, Gabriel de Arriba, Auxiliadora Mazuecos, Juan Manuel Cazorla, Mónica Pereira, Emilio González Parra, Marı́a Gabriela Márquez, Carolina Lancho Novillo, Carmen Toyos Ruiz, María Cinta Aguilar Cervera, Patricia Muñoz Ramos, Ana Sánchez Horrillo, Isabel Jimeno Martín, Néstor Toapanta, Secundino Cigarrán Guldris, Montserrat Folgueiras López, Rosalía Valero, Blanca Villacorta Linaza, Ignacio Minguela Pesquera, Raquel Santana Estupiñán, Rocío Zamora, Sagrario Soriano, E. Muñoz de Bustillo, Maria Soledad Pizarro-Sánchez, Ana Isabel Martínez Puerto, Alejandra Yugueros González, Laura Muñiz Pacios, Alba Leyva, José Antonio Muñoz Rojas, Ron T. Gansevoort, Patricia de Sequera,

Heparin-Induced Thrombocytopenia and Thrombosis

Information on the effect of a third dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in advanced CKD is incomplete (1). We assessed the humoral response up to 6 months after receipt of two or three doses of the SARS-CoV-2 vaccine across the CKD spectrum. SENCOVAC is a prospective, multicentric study of four cohorts of patients with CKD: kidney transplant, hemodialysis (HD), peritoneal dialysis (PD), and nondialysis CKD (eGFR <30 ml/min per 1.73 m2) (2,3). Patients were vaccinated against SARS-CoV-2 during routine clinical care. Some patients received a third dose of an mRNA vaccine. This depended on the timing of vaccination drives by local health authorities. We assessed anti-Spike antibodies (CLIA, Covid-19 Spike Quantitative Virclia IgG Monotest; Vircell SL, Spain) kinetics at a prespecified 6-month time point after completing the original vaccination schedule (2,3). The study was approved by the ethics committee of Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD) (February 2021). Antibody titers were assessed at 28 days in 1736 patients, 3 months in 1371 patients, and 6 months in 1008 patients. At 6 months, 175 (17%) were kidney transplant recipients, 64 (6%) were on PD, 698 (70%) were on HD, and 71 (7%) were patients with CKD. Patients had received two doses of BNT162b2 (Pfizer-BioNTech; 305, 30%) or mRNA-1273 (Moderna; 703, 70%). Additionally, 624 (65%) patients received a third dose (26% BNT162b2, 74% mRNA-1273): 118 (71%) kidney transplant recipients, 20 (37%) patients on PD, 451 (67%) patients on HD, and 35 (51%) patients with CKD. The third dose was given a median of 144 (111–170) days after the second dose (125 [85–156] days in kidney transplant recipients, 145 [125–183] days in patients on PD, 147 [115–174] days in patients on HD, and 148 [125–188] days in patients with CKD). Six months after completing the initial vaccination schedule, anti-Spike titers were lower in kidney transplant recipients than in patients on HD (P<0.001) (Figure 1A). Similarly, among patients with negative baseline anti-Spike antibodies, kidney transplant recipients had lower anti-Spike antibodies titers at 6 months than patients on HD (P<0.001). Anti-Spike antibody titers were lower in patients on PD than in those on HD (P=0.001). At 6 months, patients who had received a third vaccine dose had higher anti-Spike antibody titers than those without the third dose (P<0.001) in all CKD cohorts. Among patients who did not receive a third dose, antibody titers decreased significantly from 3 to 6 months (P 36 IU/ml). The table shows the sample size of each CKD group across each time point. Only significant P values are shown. HD, hemodialysis; PD, peritoneal dialysis.According to the manufacturer, a positive humoral response was defined as anti-Spike IgG titers >36 U/ml. A positive response at 6 months among those receiving versus not receiving a third dose, by CKD subgroup, was as follows: 94 of 118 (80%) versus 25 of 47 (53%; P=0.002) kidney transplant recipients, respectively; 20 of 20 (100%) versus 24 of 34 (71%; P=0.01) patients on PD, respectively; 432 of 451 (96%) versus 138 of 217 (64%; P<0.001) patients on HD, respectively; and 34 of 35 (97%) versus 24 of 33 (73%; P=0.02) patients with CKD, respectively (Figure 1B). These responses were higher than in patients without a third dose (P<0.001). Among patients without humoral response at 3 months, 72 (69%) seroconverted after the third dose. The percentage of seroconverted patients was numerically higher with a third dose of mRNA-1273 (58%) than of BNT162b2 (38%; P=0.07). Among the CKD cohorts, 36 of 58 (62%) kidney transplant recipients, 34 of 45 (76%) patients on HD, and two of two (100%) patients with CKD seroconverted after the third dose. In an adjusted multivariable model using logistic regression, a positive humoral response at 6 months was associated with initial mRNA-1273 vaccine (hazard ratio [HR], 1.78; 95% confidence intervals [95% CI], 1.11 to 2.88; P=0.02), a positive humoral response at 3 months (HR, 26.2; P<0.001), having received a third dose (HR, 22.9; 95% CI, 8.06 to 65.2; P<0.001), and not being a kidney transplant recipient (HR for kidney transplant recipients, 0.26; 95% CI, 0.09 to 0.73; P=0.01). In patients with 3-month negative humoral response, a third dose (HR, 27.8; 95% CI, 5.12 to 150.0; P<0.001) and not being a kidney transplant recipient (HR for kidney transplant recipients, 0.11; 95% CI, 0.02 to 0.74; P=0.02) were associated with a humoral response at 6 months in a model adjusted for age, type of initial and subsequent mRNA vaccine, and baseline anti-Spike antibodies. The limitations are a small sample size, especially for some of the CKD subgroups that did not receive a third dose; that the timing of the third dose (between the third and sixth months) was variable and not accounted for in describing these results; and that the study did not assess cellular immunity or clinical efficacy (4). In conclusion, the pragmatic analysis of the SENCOVAC study reveals that anti-Spike antibodies continue to decrease from 3 to 6 months after vaccination in patients with CKD. A third dose of SARS-CoV-2 vaccine induces seroconversion in a high percentage of antibody-negative patients with CKD after two doses, although responses were poorer in kidney transplant recipients. Disclosures C. Alfaro Sánchez and E. Orero report employment with Diaverum. D. Arroyo reports consultancy agreements with Vifor Pharma; honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gillead, GSK, Otsuka, UCB Pharma, and Vifor Pharma; and honoraria for conferences, consulting fees, and advisory boards from Amgen, AstraZeneca, Baxter, Boehringer Ingelheim, Eli Lilly, Esteve, Otsuka, Sanofi-Genzyme, and Vifor-Pharma. J.M. Cazorla has received honoraria for conferences from Astellas and AstraZeneca. S. Cigarrán Guldris reports consultancy agreements with Abbott, Boehringer, Nipro, Novartis, and Novo Nordisk; research funding from Abbott, AbbVie, Chiesi, Fresenius Medical Care, Maltrom, MSD, Nipro, and Shire; honoraria from Abbott, AbbVie, Chiesi, Fresenius Medical Care, Maltrom, MSD, Nipro, and Shire; honoraria for conferences, consulting fees, and advisory boards from Amgen, Astellas, AstraZeneca, Boehringer, Chemo-Centrix, Chiesi, Novartis, Novo Nordisk, Otsuka, Rovi, Sanofi-Genzyme, and Vifor-Pharma; serving in an advisory or leadership role for AbbVie, Maltrom, MSD, and Shire; serving on the editorial board of Journal of Diabetes Research; speakers bureau for AbbVie, AstraZeneca, MSD, Nipro, and Shire; and other interests or relationships with Sociedad Española de Nefrología. P. de Sequera reports consultancy agreements with Alexion, Astellas, AstraZeneca, Baxter, Nipro, and Vifor Pharma; research funding from Baxter; honoraria from Amgen, AstraZeneca, Baxter, Fresenius, Nipro, and Vifor Pharma; serving in an advisory or leadership role for Astellas, AstraZeneca, Baxter, and Vifor Pharma; and speakers bureau for Alexion, Amgen, AstraZeneca, Baxter, Braun, Fresenius, Nipro, and Vifor Pharma. P. de Sequera reports honoraria for conferences, consulting fees, and advisory boards from Amgen, Astellas, AstraZeneca, Baxter, Braun, Fresenius, Nipro, and Vifor-Pharma. She is the present president of the Spanish Society of Nephrology. R.T. Gansevoort reports consultancy agreements with AstraZeneca, Bayer, Galapagos, Otsuka Pharmaceutical, and Sanofi-Genzyme; research funding from AstraZeneca, Bayer, Galapagos, Otsuka Pharmaceuticals, and Sanofi-Genzyme; honoraria from Bayer, Galapagos, Mironid, Otsuka Pharmaceuticals, and Sanofi-Genzyme; and serving in an advisory or leadership role for American Journal of Kidney Diseases, CJASN, Journal of Nephrology, Kidney360, Nephrology Dialysis Transplantation, and Nephron Clinical Practice. C.C. González reports honoraria for conferences, consulting fees, and advisory boards from AstraZeneca and Fresenius and speakers bureau for AstraZeneca. C.J.J. Mantecón reports employment with Diaverum and honoraria for one conference from Vifor-Pharma. A.J. Marin Franco reports employment with and honoraria from Diaverum Servicios Renales SL. A. Mazuecos has received honoraria for conferences, consulting fees, and advisory boards from Astellas, Chiesi, GSK, Novartis, and Sanofi-Genzyme. She is a member of the Board of the Spanish Society of Nephrology and the Spanish Society of Transplantation. A. Ortiz is the director of the Catedra Mundipharma Universidad Autónoma de Madrid (UAM) of diabetic kidney disease and the Catedra AstraZeneca UAM of CKD and electrolytes; reports consultancy agreements with Genzyme, Retrophin, and Sanofi; reports research funding from AstraZeneca, Mundipharma, and Sanofi Genzyme; reports honoraria from Advicciene, Alexion, Amgen, Amicus, Astellas, AstraZeneca, Bayer, Chiesi, Fresenius Medical Care, Idorsia, Kyowa Kirin, Menarini, Otsuka, Sanofi-Genzyme, and Vifor Fresenius Medical Care Renal Pharma; reports serving in an advisory or leadership role for the Dutch Kidney Foundation Scientific Advisory Board, European Renal Association (ERA) and Sociedad Madrileña de Nefrología (SOMANE) councils, and the board of directors of Instituto de Investigación Sanitaria (IIS)-Fundacion Jimenez Diaz UAM; reports serving as a Spanish Society of Nephrology member and as Clinical Kidney Journal Editor-in-Chief; reports serving on the editorial boards of JASN, Journal of Nephrology, and Peritoneal Dialysis International; and reports speaker engagements for Advicciene, Alexion, Amgen, Amicus, Astellas, AstraZeneca, Bayer, Chiesi, Fresenius Medical Care, Idorsia, Kyowa Kirin, Menarini, Otsuka, Sanofi-Genzyme, and Vifor Fresenius Medical Care Renal Pharma. M.S. Pizarro Sánchez reports honoraria from AstraZeneca. B. Quiroga reports consultancy agreements with Amgen, Astellas, AstraZeneca, Bial, Esteve, Ferrer, Laboratorios Bial, Novartis, Otsuka, Sandoz, Sanofi-Genzyme, and Vifor-Pharma; honoraria from Amgen, Astellas, AstraZeneca, Bial, Esteve, Ferrer, Laboratorios Bial, Novartis, Otsuka, Sandoz, Sanofi-Genzyme, and Vifor-Pharma; serving in an advisory or leadership role for Amgen, Astellas, AstraZeneca, Bial, Esteve, Ferrer, Novartis, Laboratorios Bial, Otsuka, Sandoz, Sanofi-Genzyme, and Vifor-Pharma; and other interests or relationships as the secretary of the Spanish Society of Nephrology. J. Rojas report employment with Vircell SL. M.J. Soler reports consultancy agreements with AstraZeneca, Bayer, Boehringer, Esteve, ICU Medical, Jansen, Mundipharma, Novo Nordisk, and Travere Therapeutics; research funding from Abbvie and Boehringer; honoraria from AstraZeneca, Bayer, Boehringer, Esteve, FMC, ICU Medical, Ingelheim Lilly, Jansen, Mundipharma, Novo Nordisk, Otsuka, Travere, and Vifor; patents or royalties for U691ES00; serving in an advisory or leadership role on the board of American Society of Nephrology news, for Ex BMC Nephrology, for CKJ, as elected Editor-in-Chief (EIC) of Clinical Kidney Journal (CKJ), as Ex ERA-EDTA council member, as Ex-Scientific Advisory Board (SAB) the European Renal Association and the European Dialysis and Transplant Association (ERA-EDTA), for Kidney and Blood Pressure Research, and as a council member of the Spanish Society of Nephrology; speakers bureau for AstraZeneca, Bayer, Boehringer, Esteve, FMC, Jansen, Mundipharma, Novo Nordisk, and Vifor; and other interests or relationships with Sociedad Catalana de Nefrologia (member) and Sociedad Española de Nefrología. S. Soriano reports honoraria for conferences and advisory boards from Astellas, Baxter, and Vifor-Pharma. S. Tejedor reports employment with Diaverum Gamapal SL. C. Toyos Ruiz reports employment with Sociedad Española de Nefrología. All remaining authors have nothing to disclose. Funding This project has been supported by Diaverum, Fresenius Medical Care, Fundación Renal Iñigo Álvarez de Toledo, Vifor Pharma, and Vircell.