Features of COVID-19 vaccine prophylaxis in renal graft recipients

The aim of the study was to evaluate the efficacy and safety of COVID-19 vaccine prophylaxis with vaccines produced in Russia in kidney transplant recipients. Materials and methods: the study included 144 renal transplant recipients (RTR) 51.9±11.3 years old (male 66.2%). In most cases (95.8%), the Gam-COVID-Vac vaccine was used for immunization. Patients were divided into 2 groups depending on the scope of the examination: in group 1 (n=67) IgG antibodies to the receptor-binding domain of SARS-COV-2 S-protein (IgGs) were determined before and after vaccination; in group 2 (n=77) only after vaccination. The duration of follow-up after the start of immunization was 66.8±28.3 days. The effectiveness of vaccination was assessed by seroconversion in initially seronegative RTR; in patients with COVID-19 in the anamnesis - by the degree of increase in the level of antibody IgGs (>25%) after immunization. Results: 14 out of 144 (9.7%) RTR (7 patients in each group) underwent COVID-19 within 35 days after the administration of the first dose of the vaccine and were excluded from the analysis. Initially seronegative patients in group 1 failed to achieve seroconversion in 76.9% of cases, and in group 2 in 59.3% of RTR. Among seropositive patients after vaccination in both groups, the level of IgGs was significantly lower in RTR, who initially did not have IgGs, compared with patients with COVID-19 in the anamnesis: 47.5 (24.8; 133.3) BAU/ml versus 501.0 (395.4; 501.0) BAU/ml, respectively, p <0.001 in group 1 and 63.0 (41.0; 108.0) BAU/ml versus 501.0 (455.5;501.0) BAU/ml, respectively, p <0.001 in group 2. The level of IgGs antibodies in RTR group 1, who had previously COVID-19 increased from 110.5 (25.3; 244.0) BAU/ml to 501.0 (395.4; 501.0) BAU/ml (p <0.001), respectively, before and after vaccination. In general, in the long term after immunization, 7 RTR were infected with SARS-CoV-2, 6 of them were seronegative, and 1 patient with seroconversion had a low level of IgGs antibodies (32 BAU/ml); 1 patient died due to ARDS. Immunization did not affect the function of the kidney graft. Conclusions: obtained results indicate a low frequency of humoral response when using standard vaccination protocols against COVID-19 in RPT, which necessitates modification of their immunization regimens with an analysis of not only the effectiveness and safety but also the duration of protection of its enhanced variants.

трансплантация почки, реципиенты почечного трансплантата, вакцинация от COVID-19, kidney transplantation, renal graft recipients, vaccination against COVID-19

1. Cravedi P., Mothi S.S., Azzi Y. et al. COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium. Am J Transplant. 2020. 20(11):3140-3148. doi: 10.1111/ajt.16185

2. Raja M.A., Mendoza M.A., Villavicencio A. et al. COVID-19 in solid organ transplant recipients: a systematic review and meta-analysis of current literature. Transplant Rev (Orlando). 2021. 35(1):100588. doi: 10.1016/j.trre.2020.100588

3. Marinak S., Tsiakas S., Korogiannou M. et al. A systematic review of COVID-19 infection in kidney transplant recipients: a universal effort to preserve patients’ lives and allografts. J Clin Med. 2020. 9(9):2986. doi: 10.3390/jcm9092986

4. Kremer D., Pieters T.T., Verhaar M.C. et al. A systematic review and meta-analysis of COVID-19 in kidney transplant recipients: lessons to be learned. Am J Transplant. 2021. 21:3936-3945. doi: 10.1111/ajt.16742

5. Fisher A.M., Schlaoiuch D., Mulloy M. et al. Outcomes of COVID-19 in hospitalized solid organ transplant recipients compared to a matched cohort of non-transplant patients at a national healthcare system in the United States. Clin Transplant. 2021. 35(4):e14216. doi: 10.1111/ctr.14216

6. Hilbrands L.B., Duivenvoorden R., Vart P., et al. COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration. Nephrol Dial Transplant. 2020. 5(11):1973-1983. doi: 10.1093/ndt/gfaa261

7. Azzi Y., Parides M., Alani O. et al. COVID-19 infection in kidney transplant recipients at the epicenter of pandemics. Kidney Int. 2020. 98(6):1559-1567. doi: 10.1016/j.kint.2020.10.004

8. Khairallah P., Aggarwal N., Awan A.A. et al. The impact of COVID-19 on kidney transplantation and the kidney transplant recipient - One year into the pandemic. Transpl Int. 2021. 34(4):612-621. doi: 10.1111/tri.13840

9. Azzi Y., Raees H., Wang T. et al. Risks factors associated with poor response to COVID-19 vaccination in kidney transplant recipients. Kidney Int. 2021. 100(5):1127-1128. doi: 10.1016/j.kint.2021.08.019

10. Ao G., Wang Y., Qi X. et al. The association between severe or death COVID-19 and solid organ transplantation: a systematic review and meta-analysis. Transplant Rev (Orlando). 2021. 35(3):100628. doi: 10.1016/j.trre.2021.100628

11. Guan W.J., Ni Z.Y., Hu Y. et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020. 382(18):1708-1720. doi: 10.1056/NEJMoa2002032

12. Ким И.Г., Артюхина Л.Ю., Фролова Н.Ф. и др. SARS-CoV-2 инфекция у реципиентов почечного трансплантата. Нефрология и диализ. 2021. 23(2):174-184. doi: 10.28996/2618-9801-2021-2-174-184

13. Pfizer and BioNTech conclude phase 3 study of COVID-19 vaccine candidate, meeting all primary efficacy endpoints. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine. Accessed 18 Nov 2020.

14. Promising interim results from clinical trial of NIH Moderna COVID-19 Vaccine. In: National Institutes of Health (NIH). https://www.nih.gov/news-events/news-releases/promising-interim-results-clinical-trial-nih-moderna-covid-19-vaccine. Accessed 25 Nov 2020.

15. Logunov D.Y., Dolzhikova I.V., Zubkova O.V. et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020. 3969(10255):887-897. doi: 10.1016/S0140-6736(20)31866-3

16. Logunov D.Y., Dolzhikova I.V., Shcheblyakov D.V. et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet. 2021. 397(10275):671-681. doi: 10.1016/S0140-6736(20)31866-3

17. Voysey M., Clemens S.A.C., Madhi S.A. et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021. 397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1

18. Sadoff J., Gray G., Ch B. et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. N Engl J Med. 2021. 384(23):2187-2201. doi: 10.1056/NEJMoa2101544

19. Nordström P., Ballin M., Nordström A. et al. Risk of infection, hospitalisation, and death up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total population cohort study in Sweden. Lancet. 2022. 399(10327):814-823. doi: 10.1056/NEJMoa2101544

20. Chia P.Y., Ong S.W.X., Chiew C.J. et al. Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study. Clin Microbiol Infect. 2022. 28(4):612.e1-612.e7. doi: 10.1016/j.cmi.2021.11.010

21. 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(9):2147-2152. doi: 10.1681/ASN.2021040480

22. 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(10):e142-e143. DOI: 10.1097/TP.0000000000003892

23. Boyarsky B.J., Werbel W.A., Avery R.K. et al. Immunogenicity of a Single Dose of SARS CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients. JAMA. 2021 325(17):1784-1786. doi:10.1001/jama.2021.4385

24. Boyarsky B.J., Werbel W.A., Avery R.K. et al. Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients. JAMA. 2021. 325(21): 204-2206. doi:10.1001/jama.2021.7489

25. Marion O., Del Bello A., Abravanel F. et al. Safety and immunogenicity of anti-SARS-CoV-2 messenger RNA vaccines in recipients of solid organ transplants. Ann Intern Med. 2021. 174(9):1336-1338. doi: 10.7326/M21-1341

26. 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(8):2719-2726. doi: 10.1111/ajt.16615.

27. 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(6):1498-1500. doi: 10.1016/j.kint.2021.04.005

28. Rincon-Arevalo H., Choi M., Stefanski A.L. et al. Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients. Sci Immunol. 2021. 6(60):eabj1031. doi: 10.1126/sciimmunol.abj1031

29. 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(8):1173.e1-1173.e4. doi: 10.1016/j.cmi.2021.04.028

30. 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(8):2727-2739. doi: 10.1111/ajt.16701

31. Lee A.R.Y.B., Wong S.Y., Chai L.Y.A. et al. Efficacy of COVID-19 vaccines in immunocompromised patients: a systematic review and meta-analysis. BMJ. 2022. 376:e068632. doi: 10.1136/bmj-2021-068632

32. Stumpf J., Siepmannb T., Lindner T. et al. Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine. Lancet Reg Health Eur. 2021. 9:100178. doi: 10.1016/j.lanepe.2021.100178

33. Bertrand D., Laurent C., Lemée V. et al. Efficacy of anti-SARS-CoV-2 monoclonal antibody prophylaxis and vaccination on the Omicron variant of COVID-19 in kidney transplant recipients. Kidney Int. 2022. 102(2):440-442. doi: 10.1016/j.kint.2022.05.007

34. 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(7):661-662. doi: 10.1056/NEJMc2108861

35. Jalali V., Scherzer S., Zeitlinger M. Improved immunogenicity against SARS-CoV-2 in a solid-organ transplant recipient by switching vaccines. Letter to the Editor. Clin Micr Infect. 2021. 27(10):1529-1530. doi: 10.1016/j.cmi.2021.06.022

36. Hall V.G., Ferreira V.H., Ku T. et al. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. N Engl J Med. 2021. 385(13):1244-1246. doi: 10.1056/NEJMc2111462

37. Parker E.P.K., Desai Sh., Marti M. et al. Response to additional COVID-19 vaccine doses in people who are immunocompromised: a rapid review. Lancet. 2022. 10(3):E326-E328. doi: 10.1016/S2214-109X(21)00593-3

38. Werbel W.A., Boyarsky B.J., Ou M.T. 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(9):1330-1332. doi: 10.7326/L21-0282

39. Interim recommendations for an extended primary series with an additional vaccine dose for COVID-19 vaccination in immunocompromised persons. Interim guidance. WHO. 26 October 2021, available on the SAGE COVID-19 webpage: https://www.who.int/groups/strategic-advisory-group-of-experts-on-immunization/covid-19-materials.