BACKGROUND: Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been recently shown to be impaired in kidney transplant recipients (KTRs), but the underlying factors affecting vaccine effectiveness need to be further elucidated. METHODS: In this prospective cohort study, antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%) in 736 KTRs, who were previously either naive or infected with SARS-CoV-2 and vaccinated before or after transplantation. Cellular response was analyzed in a subset of patients using an interferon gamma release assay (cutoff 0.15 IU/mL, sensitivity 92%, and specificity 100%). RESULTS: Seroconversion was significantly more impaired in SARS-CoV-2-naive KTRs than in those previously infected (40.1% versus 97.1%; P < 0.001). Mycophenolate use (odds ratio, 0.15; 95% confidence interval, 0.09-0.24; P < 0.001) and depleting therapy in the past year (odds ratio, 0.19; 95% confidence interval, 0.05-0.8; P = 0.023) were found to be among independent factors associated with impaired humoral response. Similarly, the interferon gamma release assay tested in 50 KTRs (cutoff 0.15 IU/mL, sensitivity 92%, specificity 100%) showed that specific T-cell responses against spike protein epitopes are impaired in SARS-CoV-2-naive KTRs, as compared to previously infected KTRs (9.4% versus 90%, P < 0.001). All 35 KTRs vaccinated on the waiting list before transplantation exhibited sustained seroconversion persisting after transplantation. CONCLUSIONS: Survivors of coronavirus disease 2019 and those vaccinated while on the waiting list exhibited a marked immune response to mRNA vaccines, contrary to poor response in naive KTRs vaccinated after transplantation (NCT04832841).

Department of Immunology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Nephrology Transplant Center Institute for Clinical and Experimental Medicine Prague Czech Republic

Division of Hygiene and Epidemiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Information Technology Department Institute for Clinical and Experimental Medicine Prague Czech Republic

Institutional Pharmacy Institute for Clinical and Experimental Medicine Prague Czech Republic

Transplantation Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic

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Akalin E, Azzi Y, Bartash R, et al. . Covid-19 and kidney transplantation. N Engl J Med. 2020;382:2475–2477. PubMed PMC

Haas EJ, Angulo FJ, McLaughlin JM, et al. . Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet. 2021;397:1819–1829. PubMed PMC

Amit S, Regev-Yochay G, Afek A, et al. . Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 vaccine recipients. Lancet. 2021;397:875–877. PubMed PMC

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. PubMed PMC

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. PubMed PMC

Walsh EE, Frenck RW, Jr, Falsey AR, et al. . Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383:2439–2450. PubMed PMC

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. PubMed PMC

Devresse A, Saad Albichr I, Georgery H, et al. . T-cell and antibody response after 2 doses of the BNT162b2 vaccine in a belgian cohort of kidney transplant recipients. Transplantation. 2021;105:e142–e143. PubMed PMC

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. PubMed PMC

Magicova M, Fialova M, Zahradka I, et al. . Humoral response to SARS-CoV-2 is well preserved and symptom dependent in kidney transplant recipients. Am J Transplant. 2021;21:3926–3935. PubMed PMC

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. PubMed PMC

Cucchiari D, Egri N, Bodro M, et al. . Cellular and humoral response after MRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients. Am J Transplant. 2021;21:2727–2739. PubMed PMC

Georgery H, Devresse A, Yombi J-C, et al. . Disappointing immunization rate after 2 doses of the BNT162b2 vaccine in a Belgian cohort of kidney transplant recipients. Transplantation. 2021;105:e283–e284. PubMed PMC

Anichini G, Terrosi C, Gandolfo C, et al. . SARS-CoV-2 antibody response in persons with past natural infection. N Engl J Med. 2021;385:90–92. PubMed PMC

Havlin J, Svorcova M, Dvorackova E, et al. . Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients. J Heart Lung Transplant. 2021;40:754–758. PubMed PMC

Bonelli F, Sarasini A, Zierold C, et al. . Clinical and analytical performance of an automated serological test that identifies S1/S2-neutralizing IgG in COVID-19 patients semiquantitatively. J Clin Microbiol. 2020;58:e01224–20. PubMed PMC

The National SARS-CoV-2 Serology Assay Evaluation Group. Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison. Lancet Infect Dis. 2020;20:1390–1400. PubMed PMC

National Institutes of Health. Clinical spectrum of SARS-CoV-2 infection. COVID-19 Treatment Guidelines Panel. 2021. Available at https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/. Accessed September 25, 2021. PubMed

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. PubMed PMC

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. PubMed PMC

Danthu C, Hantz S, Dahlem A, et al. . Humoral response after SARS-CoV-2 mRNA vaccination in a cohort of hemodialysis patients and kidney transplant recipients. J Am Soc Nephrol. 2021;32:2153–2158. PubMed PMC

Baluch A, Humar A, Eurich D, et al. . Randomized controlled trial of high-dose intradermal versus standard-dose intramuscular influenza vaccine in organ transplant recipients. Am J Transplant. 2013;13:1026–1033. PubMed

Egli A, Humar A, Widmer LA, et al. . Effect of immunosuppression on T-helper 2 and B-cell responses to influenza vaccination. J Infect Dis. 2015;212:137–146. PubMed

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. PubMed PMC

Stumpf J, Tonnus W, Paliege A, et al. . Cellular and humoral immune responses after 3 doses of BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant. Transplantation. 2021;105:e267–e269. PubMed PMC

Alejo JL, Mitchell J, Chiang TPY, et al. . Antibody response to a fourth dose of a SARS-CoV-2 vaccine in solid organ transplant recipients: a case series. Transplantation. 2021;105:e280–e281. PubMed PMC

American Society of Transplantation. Updated Joint AST/ASTS/ISHLT Statement about vaccine efficacy in organ transplant recipients. 2021. Available at https://www.myast.org/statement-covid-19-vaccination-solid-organ-transplant-recipients. Accessed July 14, 2021.

Saadat S, Rikhtegaran Tehrani Z, Logue J, et al. . Binding and neutralization antibody titers after a single vaccine dose in health care workers previously infected with SARS-CoV-2. JAMA. 2021;325:1467–1469. PubMed PMC

Stamatatos L, Czartoski J, Wan YH, et al. . mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection. Science. 2021;372:1413–1418. PubMed PMC

Reynolds CJ, Pade C, Gibbons JM, et al. . Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose. Science. 2021;372:1418–1423. PubMed PMC

Boyarsky BJ, Barbur I, Chiang TP, et al. . SARS-CoV-2 messenger RNA vaccine immunogenicity in solid organ transplant recipients with prior COVID-19. Transplantation. 2021;105:e270–e271. PubMed PMC

Barros-Martins J, Hammerschmidt SI, Cossmann A, et al. . Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination. Nat Med. 2021;27:1525–1529. PubMed PMC

Boyarsky BJ, Werbel WA, Avery RK, et al. . Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–2206. PubMed PMC

Steensels D, Pierlet N, Penders J, et al. . Comparison of SARS-CoV-2 antibody response following vaccination with BNT162b2 and mRNA-1273. JAMA. 2021;326:1533–1535. PubMed PMC

Viklicky O, Fronek J, Trunecka P, et al. . Organ transplantation in the czech republic. Transplantation. 2017;101:2259–2261. PubMed

Burack D, Pereira MR, Tsapepas DS, et al. . Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection. Am J Transplant. 2021;21:2254–2261. PubMed PMC

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ClinicalTrials.gov
NCT04832841