Humoral Response To BNT162b2 MRNA SARS-CoV-2 Vaccine in Patients With Nondialysis Chronic Kidney Disease

Delphine Kervella,Pierre Braud, Claire Garandeau, Celine Phelizot, Xavier Ambrosi,Gilles Blancho, Maryvonne Hourmant, Lucile Figueres ,  and the Divat Consortium* CJASN 16: 1872–1874, 2021. 

Patients with severe CKD have been excluded from major vaccine trials (1). So far, immune response to coronavirus disease 2019 vaccination in non-transplanted, nondialyzed patients with CKD has not been determined and raises questions given their known under-responsiveness to vaccination.

We assessed the serologic response of patients with CKD from our center 1 month after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination (BNT162b2 Pfifizer/BioNTech Comirnaty, two doses, 3 to 6 weeks apart). Kidney transplant recipients and patients undergoing maintenance dialysis were excluded. Patients with CKD stage 3b, 4, or 5 (eGFR below 45 ml/min per 1.73 m2 ) with a negative pre-vaccinal anti-protein N serology and monitoring of anti-Spike receptor-binding domain (RBD) IgGs (Electrochemiluminescence Immunoassay; Roche Elecsys) 1 month after the second dose were included. Patients were classified as “responders” (anti-Spike RBD IgGs above 30 binding antibody units [BAU]/ml) and “nonresponders.”

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We retrospectively collected serology results and biological and clinical data from patients vaccinated between January and May 2021, including the use of immunosuppressive therapy at the time of vaccination and rituximab therapy within 6 months before vaccination. The Wilcoxon test (quantitative variables, P#0.05 considered as significant) and the Fisher exact test (qualitative variables, P#0.05 considered as significant) were performed using “R studio version 1.3.1056.”

Seventy-five patients were included in the study. The median time between the two BNT162b2 injections was 28 days (interquartile range [IQR], 26–28), whereas the median time between the second injection and anti-Spike RBD IgGs measurement was 31 days (IQR, 31–37). Anti-Spike RBD IgGs were detectable in 69 patients (92%), six patients had a negative postvaccinal serology (8% of the cohort), and six (8%) had a low immune response (anti-Spike RBD IgGs below 30 BAU/ml). Thus, nonresponders represent 16% of our cohort (12 patients). All nonresponders had signifies- cantly lower lymphocyte counts than responders, despite similar white blood cell counts (Table 1) (P50.003). There was a strong association between chronic immunosuppressive treatment and nonresponse (P,0.001). All nonresponders had lymphopenia, even in patients without chronic immunosuppressive therapy (median lymphocytes count in these five patients was 1.27 G/L; IQR, 0.99–1.45).

All six patients with a negative postvaccinal serology had significant comorbidities: two were solid organ transplant recipients (liver and heart-lung), one suffered from a neuroendocrine tumor, and three were treated with rituximab (two for ANCA-associated vasculitis, and one for lymphoma). Two patients treated with rituximab therapy received the treatment in the month preceding vaccination, and one received it 6 months before. There were no responders with a history of solid organ transplantation or treatment with rituximab within the past 6 months.

On the basis of our data, lymphocyte count below 1.3 G/L associated with chronic immunosuppressive therapy was highly predictive of a poor immune response in patients with CKD (receiver operating characteristic curve analysis to set the lymphocytes count threshold; sensitivity, 45%; specificity, 100%; positive predictive value, 100%; negative predictive value, 91%).

In this first description of SARS-CoV-2 mRNA vaccine serologic response in nondialyzed, non-transplanted patients with CKD, we report a high rate of immunization following two doses of BNT162b2. Although we cannot conclude yet on vaccine efficacy in this population (lack of postvaccination SARS-CoV- 2 infection rate in patients with CKD), these data are encouraging. They are consistent with those reported in patients on dialysis, showing an overall good serologic response to two BNT162b2 injections (2). Effifi- ciency of SARS-CoV-2 mRNA vaccination needs to be studied in larger cohorts of patients with CKD (3). Moreover, ongoing studies are trying to define protective thresholds for anti-Spike RBD IgGs by correlating serology results with neutralizing antibodies (4). The emergence of variants may, however, change those thresholds. Postvaccinal serology may help to point out high-risk patients with CKD and immunity system impairment due to their comorbidities or treatment who may need the same management as transplanted patients (three to four vaccine injections).

Disclosures

G. Blancho reports consultancy agreements with Astellas and Novartis, receiving honoraria from Astellas and Novartis, and serving as a scientific advisor or member of Novartis. M. Hourm ant reports ownership interest in Sanofifi. All remaining authors have nothing to disclose.

Funding

None.

References

1. Windpessl M, Bruchfeld A, Anders H-J, Kramer H, Waldman M, Renia L, Ng LFP, Xing Z, Kronbichler A: COVID-19 vaccines and kidney disease. Nat Rev Nephrol 17: 291–293, 2021

2. Attias P, Sakhi H, Rieu P, Soorkia A, Assayag D, Bouhroum S, Nizard P, El Karoui K: Antibody response to the BNT162b2 vaccine in maintenance hemodialysis patients. Kidney Int 99: 1490–1492, 2021 

3. Kho MML, Reinders MEJ, Baan CC, van Baarle D, Bemelman FJ, Diavatopoulos DA, Gansevoort RT, van der Klis FRM, Koopmans MPG, Messchendorp AL, van der Molen RG, Remmerswaal EBM, Rots N, Vart P, de Vries RD, Hilbrands LB, Sanders JF; RECOVAC Collaborators: The RECOVAC IR study: The immune response and safety of the mRNA-1273 COVID-19 vaccine in patients with chronic kidney disease, on dialysis, or living with a kidney transplant - A prospective, controlled, multicenter observational cohort by the REnal patient's COVID-19 VACcination (RECOVAC) consortium COVID-19 VACcination (RECOVAC) consortium [published online ahead of print May 26, 2021]. Nephrol Dial Transplant

4. Trougakos IP, Terpos E, Zirou C, Sklirou AD, Apostolakou F, Gumeni S, Charitaki I, Papanagnou ED, Bagratuni T, Liacos CI, Scorilas A, Korompoki E, Papassotiriou I, Kastritis E, Dimopoulos MA: Comparative kinetics of SARS-CoV-2 anti-spike protein RBD IgGs and neutralizing antibodies in convalescent and naïve recipients of the BNT162b2 mRNA vaccine versus COVID-19 patients. BMC Med 19: 208, 2021 

*The Divat Consortium members include Gilles Blancho, Julien Branchereau, Diego Cantarovich, Agnes Chapelet, Jacques Dantal, Clement Deltombe, Lucile Figueres, Raphael Gaisne, Claire Garandeau, Magali Giral, Caroline Gourraud-Vercel, Maryvonne Hourmant, Georges Karam, Clarisse Kerleau, Delphine Kervella, Christophe Masset, Aurelie Meurette, Simon Ville, Christine Kandell, Anne Moreau, Karine Renaudin, Florent Delbos, Alexandre Walencik, and Anne Devis. M.H. and L.F. contributed equally to this work. Published online ahead of print. Publication date available at www.cjasn.org

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