A prospective observational study for justification, safety, and efficacy of a third dose of mRNA vaccine in patients receiving maintenance hemodialysis.

Anne Ovize, Olivier Thaunat, Cécile Couchoud, Denis Fouque, Laurent Juillard, Emmanuel Morelon, Laurence Pellegrina, Christine Bouz, Emmanuelle Cart-Tanneur, Maxime Espi, Virginie Mathias, Emilie Kalbacher, Elodie Chalencon, Laetitia Koppe, Caroline Pelletier, Cyrille Mathieu, Thomas Barba, Xavier Charmetant

Journal: Kidney international 2022;101(2):390-402

PMID: 34856313

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Abstract

The level of protection achieved by the standard two doses of COVID-19 mRNA vaccines in patients receiving maintenance hemodialysis (MHD) remains unclear. To study this we used the French Renal Epidemiology and Information Network (REIN) Registry to compare the incidence and severity of 1474 cases of COVID-19 diagnosed in patients receiving MHD after none, one or two doses of vaccine. Vaccination significantly reduce COVID-19 incidence and severity, but 11% of patients infected after two doses still died. Lack of vaccinal protection in patients naïve for SARS-CoV-2 could be due to defective Tfh response [38% of patients with negative spike-specific CD4 T-cell interferon gamma release assay] and failure to generate viral neutralizing titers of anti-spike receptor binding domain (RBD) IgGs (63% of patients with titer at or under 997 BAU/ml, defining low/no responders) after two doses of vaccine. To improve protection, a third dose of vaccine was administered to 75 patients [57 low/no responders, 18 high responders after two doses] from the ROMANOV cohort that prospectively enrolled patients receiving MHD vaccinated with BNT162b2 (Pfizer). Tolerance to the third dose was excellent. High responders to two doses did not generate more anti-RBD IgGs after three doses but had more side effects. Importantly, 31 (54%) of low/no responders to two doses reached neutralizing titers of anti-RBD IgGs after three doses. A positive interferon gamma release assay and/or suboptimal titer of anti-RBD IgGs after two doses were the only predictive variables for response to three doses in multivariate analysis. Thus, the standard scheme of vaccination insufficiently protects patients receiving MHD. Anti-RBD IgG and specific CD4 T-cell response after two doses can guide personalized administration of the third dose, which improves the humoral response of SARS-CoV-2-naïve patients receiving MHD.

Address: Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Claude Bernard Lyon I, Centre National de la Recherche Scientifique Unité Mixte de Recherch 5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France; Department of Nephrology, Nutrition, and Hemodialysis, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France.; Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Claude Bernard Lyon I, Centre National de la Recherche Scientifique Unité Mixte de Recherch 5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France.; Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Claude Bernard Lyon I, Centre National de la Recherche Scientifique Unité Mixte de Recherch 5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France; Department of Internal Medicine, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France; Medical School, Claude Bernard University (Lyon 1), Villeurbanne, France.; Department of Nephrology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.; Department of Nephrology, Nutrition, and Hemodialysis, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Medical School, Claude Bernard University (Lyon 1), Villeurbanne, France.; Department of Nephrology, Nutrition, and Hemodialysis, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France.; Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Claude Bernard Lyon I, Centre National de la Recherche Scientifique Unité Mixte de Recherch 5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France; Human Leukocyte Antigen Laboratory, French National Blood Service, Décines-Charpieu, France.; Eurofins Biomnis Laboratory, Lyon, France.; Medical School, Claude Bernard University (Lyon 1), Villeurbanne, France; Department of Transplantation, Nephrology, and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.; Medical School, Claude Bernard University (Lyon 1), Villeurbanne, France; Department of Nephrology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.; REIN Registry, Agence de la Biomédecine, Saint-Denis La Plaine, France; Biostatistique Santé Department, Laboratoire de Biométrie et Biologie Evolutive, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5558, Université Lyon I, Villeurbanne, France.; Centre International de Recherche en Infectiologie, Institut National de la Santé et de la Recherche Médicale U1111, Université Claude Bernard Lyon I, Centre National de la Recherche Scientifique Unité Mixte de Recherch 5308, Ecole Normale Supérieure de Lyon, Université Lyon, Lyon, France; Medical School, Claude Bernard University (Lyon 1), Villeurbanne, France; Department of Transplantation, Nephrology, and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. Electronic address: [email protected].

DOI: 10.1016/j.kint.2021.10.040