The RECOVAC Immune-response Study: The Immunogenicity, Tolerability, and Safety of COVID-19 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant
Jan-Stephan F Sanders, Frederike J Bemelman, A Lianne Messchendorp, Carla C Baan, Debbie van Baarle, Rob van Binnendijk, Dimitri A Diavatopoulos, Sophie C Frölke, Daryl Geers, Corine H GeurtsvanKessel, Gerco den Hartog, Marieke van der Heiden, Celine Imhof, Marcia M L Kho, Marion P G Koopmans, S Reshwan K Malahe, Wouter B Mattheussens, Renate van der Molen, Djenolan van Mourik, Ester B M Remmerswaal, Nynke Rots, Priya Vart, Rory D de Vries, Ron T Gansevoort, Luuk B Hilbrands, Marlies E J Reinders, RECOVAC Collaborators, Jan-Stephan F Sanders, Frederike J Bemelman, A Lianne Messchendorp, Carla C Baan, Debbie van Baarle, Rob van Binnendijk, Dimitri A Diavatopoulos, Sophie C Frölke, Daryl Geers, Corine H GeurtsvanKessel, Gerco den Hartog, Marieke van der Heiden, Celine Imhof, Marcia M L Kho, Marion P G Koopmans, S Reshwan K Malahe, Wouter B Mattheussens, Renate van der Molen, Djenolan van Mourik, Ester B M Remmerswaal, Nynke Rots, Priya Vart, Rory D de Vries, Ron T Gansevoort, Luuk B Hilbrands, Marlies E J Reinders, RECOVAC Collaborators
Abstract
Background: In kidney patients COVID-19 is associated with severely increased morbidity and mortality. A comprehensive comparison of the immunogenicity, tolerability, and safety of COVID-19 vaccination in different cohorts of kidney patients and a control cohort is lacking.
Methods: This investigator driven, prospective, controlled multicenter study included 162 participants with chronic kidney disease (CKD) stages G4/5 (eGFR < 30 mL/min/1.73m2), 159 participants on dialysis, 288 kidney transplant recipients, and 191 controls. Participants received 2 doses of the mRNA-1273 COVID-19 vaccine (Moderna). The primary endpoint was seroconversion.
Results: Transplant recipients had a significantly lower seroconversion rate when compared with controls (56.9% versus 100%, P < 0.001), with especially mycophenolic acid, but also, higher age, lower lymphocyte concentration, lower eGFR, and shorter time after transplantation being associated with nonresponder state. Transplant recipients also showed significantly lower titers of neutralizing antibodies and T-cell responses when compared with controls. Although a high seroconversion rate was observed for participants with CKD G4/5 (100%) and on dialysis (99.4%), mean antibody concentrations in the CKD G4/5 cohort and dialysis cohort were lower than in controls (2405 [interquartile interval 1287-4524] and 1650 [698-3024] versus 3186 [1896-4911] BAU/mL, P = 0.06 and P < 0.001, respectively). Dialysis patients and especially kidney transplant recipients experienced less systemic vaccination related adverse events. No specific safety issues were noted.
Conclusions: The immune response following vaccination in patients with CKD G4/5 and on dialysis is almost comparable to controls. In contrast, kidney transplant recipients have a poor response. In this latter, patient group development of alternative vaccination strategies are warranted.
Trial registration: ClinicalTrials.gov NCT04741386.
Conflict of interest statement
The authors declare no conflicts of interest
Copyright © 2021 The Author(s).
Figures
References
- Williamson EJ, Walker AJ, Bhaskaran K, et al. . Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584:430–436.
- ERA-EDTA Council; ERACODA Working Group. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA. Nephrol Dial Transplant. 2021;36:87–94.
- Baden LR, El Sahly HM, Essink B, et al. ; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384:403–416.
- Polack FP, Thomas SJ, Kitchin N, et al. ; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603–2615.
- Reddy S, Chitturi C, Yee J. Vaccination in chronic kidney disease. Adv Chronic Kidney Dis. 2019;26:72–78.
- Marinaki S, Adamopoulos S, Degiannis D, et al. . Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients. Am J Transplant. 2021;21:2913–2915.
- Grupper A, Sharon N, Finn T, et al. . Humoral response to the pfizer BNT162b2 vaccine in patients undergoing maintenance hemodialysis. Clin J Am Soc Nephrol. 2021;16:1037–1042.
- Bertrand D, Hamzaoui M, Lemée V, et al. . Antibody and T cell response to SARS-CoV-2 messenger RNA BNT162b2 vaccine in kidney transplant recipients and hemodialysis patients. J Am Soc Nephrol. 2021;32:2147–2152.
- Boyarsky BJ, Werbel WA, Avery RK, et al. . Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021;325:1784–1786.
- Kho MML, Reinders MEJ, Baan CC, et al. ; 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. Nephrol Dial Transplant. 2021;36:1761–1764.
- den Hartog G, Schepp RM, Kuijer M, et al. . SARS-CoV-2-specific antibody detection for seroepidemiology: a multiplex analysis approach accounting for accurate seroprevalence. J Infect Dis. 2020;222:1452–1461.
- den Hartog G, Vos ERA, van den Hoogen LL, et al. . Persistence of antibodies to SARS-CoV-2 in relation to symptoms in a nationwide prospective study. Clin Infect Dis. 2021;73:2155–2162.
- Geers D, Shamier MC, Bogers S, et al. . SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees. Sci Immunol. 2021;6:eabj1750.
- Okba NMA, Müller MA, Li W, et al. . Severe acute respiratory syndrome coronavirus 2-specific antibody responses in coronavirus disease patients. Emerg Infect Dis. 2020;26:1478–1488.
- Wajnberg A, Amanat F, Firpo A, et al. . Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020;370:1227–1230.
- Van Praet JT, Vandecasteele S, De Roo A, et al. . Humoral and cellular immunogenicity of the BNT162b2 mRNA Covid-19 vaccine in nursing home residents. Clin Infect Dis. 2021;73:2145–2147.
- Chavarot N, Ouedrani A, Marion O, et al. . Poor anti-SARS-CoV-2 humoral and T-cell responses after 2 injections of mRNA vaccine in kidney transplant recipients treated with belatacept. Transplantation. 2021;105:e94–e95.
- Korth J, Jahn M, Dorsch O, et al. . Impaired humoral response in renal transplant recipients to SARS-CoV-2 vaccination with BNT162b2 (Pfizer-BioNTech). Viruses. 2021;13:756.
- Rozen-Zvi B, Yahav D, Agur T, et al. . Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study. Clin Microbiol Infect. 2021;27:1173.e1–1173.e4.
- Benotmane I, Gautier-Vargas G, Cognard N, et al. . Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine. Kidney Int. 2021;99:1498–1500.
- Khoury DS, Cromer D, Reynaldi A, et al. . Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27:1205–1211.
- Sattler A, Schrezenmeier E, Weber UA, et al. . Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients. J Clin Invest. 2021;131:150175.
- Grupper A, Rabinowich L, Schwartz D, et al. . Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant. 2021;21:2719–2726.
- Furer V, Eviatar T, Zisman D, et al. . Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study. Ann Rheum Dis. 2021;80:1330–1338.
- Mulley WR, Visvanathan K, Hurt AC, et al. . Mycophenolate and lower graft function reduce the seroresponse of kidney transplant recipients to pandemic H1N1 vaccination. Kidney Int. 2012;82:212–219.
- Agur T, Ben-Dor N, Goldman S, et al. . Antibody response to mRNA SARS-CoV-2 vaccine among dialysis patients—a prospective cohort study. Nephrol Dial Transplant. 2021;36:1347–1349.
- Frantzen L, Cavaillé G, Thibeaut S, et al. . Efficacy of the BNT162b2 mRNA COVID-19 vaccine in a haemodialysis cohort. Nephrol Dial Transplant. 2021;36:1756–1757.
- Yanay NB, Freiman S, Shapira M, et al. . Experience with SARS-CoV-2 BNT162b2 mRNA vaccine in dialysis patients. Kidney Int. 2021;99:1496–1498.
- Attias P, Sakhi H, Rieu P, et al. . Antibody response to the BNT162b2 vaccine in maintenance hemodialysis patients. Kidney Int. 2021;99:1490–1492.
- Simon B, Rubey H, Treipl A, et al. . Haemodialysis patients show a highly diminished antibody response after COVID-19 mRNA vaccination compared with healthy controls. Nephrol Dial Transplant. 2021;36:1709–1716.
- United States Renal Data System. USRDS annual data report: epidemiology of kidney disease in the United States. 2020. Available at . Accessed July 23, 2021.
- Anderson EJ, Rouphael NG, Widge AT, et al. ; mRNA-1273 Study Group. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020;383:2427–2438.
- Feng S, Phillips DJ, White T, et al. ; Oxford COVID Vaccine Trial Group. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. medRxiv. [Epub ahead of print. June 24, 2021]. doi: 10.1101/2021.06.21.21258528.
- Gilbert PB, Montefiori DC, McDermott A, et al. . Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy trial. medRxiv. [Epub ahead of print. August 15, 2021]. doi: 10.1101/2021.08.09.21261290
- Werbel WA, Boyarsky BJ, Ou MT, et al. . Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: a case series. Ann Intern Med. 2021;174:1330–1332.
- Kamar N, Abravanel F, Marion O, et al. . Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med. 2021;385:661–662.
- Hall VG, Ferreira VH, Ku T, et al. . Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. N Engl J Med. 2021;385:1244–1246.
- Mombelli M, Rettby N, Perreau M, et al. . Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: a randomized controlled trial. Vaccine. 2018;36:6163–6169.
- Bel’eed K, Wright M, Eadington D, et al. . Vaccination against hepatitis B infection in patients with end stage renal disease. Postgrad Med J. 2002;78:538–540.
- Stock PG, Henrich TJ, Segev DL, et al. . Interpreting and addressing suboptimal immune responses after COVID-19 vaccination in solid-organ transplant recipients. J Clin Invest. 2021;131:151178.
- Clarke CL, Prendecki M, Dhutia A, et al. . Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection. Kidney Int. 2021;99:1470–1477.
- Thieme CJ, Anft M, Paniskaki K, et al. . The magnitude and functionality of SARS-CoV-2 reactive cellular and humoral immunity in transplant population is similar to the general population despite immunosuppression. Transplantation. 2021;105:2156–2164.
- Firket L, Descy J, Seidel L, et al. . Serological response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients depends on prior exposure to SARS-CoV-2. Am J Transplant. 2021;21:3806–3807.
Source: PubMed