Der Einfluss von Immunsuppression und chronischen Nierenerkrankungen auf das Ansprechen auf COVID-19-Impfungen

 

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Wie effektiv sind die zugelassenen Impfstoffe bei Nierenerkrankungen und Immunsupprimierten? Zahlreiche Beobachtungsstudien legen nahe, dass vor allem eine systemische Immunsuppression eine geringe oder fehlende Antikörperbildung bedingt. Auch Patienten mit fortgeschrittener chronischer Nierenerkrankung, insbesondere mit Dialysepflichtigkeit, ohne Einnahme systemischer Immunsuppressiva haben ein reduziertes humorales Ansprechen.

Ich habe eine COVID-19-Erkrankung durchgemacht. Ist für mich eine COVID-19-Impfung sinnvoll? Nach durchgemachter COVID-19-Erkrankung scheint auch für Nierenkranke eine Boosterung mit einem mRNA-Impfstoff sinnvoll zu sein.

Kann ich trotz laufender Immunsuppression geimpft werden? Für Patienten unter Immunsuppression ist das Ansprechen auf Impfstoffe reduziert. Dennoch sollten sie geimpft werden. Eine Anti-CD20-Therapie beeinträchtigt die humorale Immunantwort erheblich.

Besteht die Möglichkeit einer Abstoßungsreaktion meines Transplantats bzw. eines Rezidivs der Grunderkrankung? Im Zuge der globalen Impfanstrengungen erscheinen nun einzelne Berichte über Erstmanifestationen, Schübe oder Krankheitsrezidive über das Spektrum autoimmuner Nierenerkrankungen, die in zeitlichem Zusammenhang mit der Impfung stehen. Da die meisten Rezidive/Abstoßungen behandelbar sind, der Verlauf einer COVID-19-Erkrankung aber oftmals schwer bzw. tödlich ist, überwiegt der Nutzen die Risiken.

Habe ich eine dauerhafte Protektion nach erfolgter COVID-19-Impfung? Im Vergleich zur altersentsprechenden gesunden Population weist die nephrologische Patientengruppe nach Impfung deutlich niedrigere Titer auf, welche auch rascher abnehmen (vor allem Evidenz für Transplantierte und Dialyse). Eine frühzeitige Auffrischung sollte auch aufgrund der besorgniserregenden Virusvarianten und der reduzierten Wirksamkeit der Impfstoffe erwogen werden.

Nach der ersten Impfserie haben sich keine/kaum Antikörper nachweisen lassen. Gibt es Strategien, die Impfantwort zu verbessern? Viele Länder empfehlen eine 3. Impfdosis für vulnerable Populationen, v. a. auch wegen der reduzierten Antwort nach 2 Dosen bzw. auch des Risikos eines schweren Verlaufs einer COVID-19-Erkrankung. Der Einsatz einer Drittimpfung muss aber im Rahmen prospektiver klinischer Studien überprüft werden.

Abstract

How effective are the approved vaccines in kidney diseases and those receiving immunosuppression? Several observational studies indicated that immunosuppression is associated with a weakened or absent humoral response. Patients with chronic kidney diseases or undergoing maintenance dialysis without immunosuppression have a reduced humoral response to COVID-19 vaccines.

I had COVID-19. Should I get vaccinated? It is recommended to receive a booster after SARS-CoV-2 infection with a mRNA vaccine.

Is a COVID-19 vaccination despite ongoing immunosuppression possible? Patients receiving immunosuppression have a reduced humoral response, and this is especially observed when anti-CD20 therapy is used.

Is there a possibility that the vaccine provokes rejection of my transplanted kidney or relapse of my glomerular disease? Several reports were published in the last months highlighting new-onset diseases, recurrences and relapses of different glomerular diseases, which occurred after the receipt of the first or second vaccine dose. As a clear association of vaccines and induction of autoimmunity still needs to be established, most of these diseases are treatable, and COVID-19 in patients under immunosuppression is often fatal, there is a clear net benefit of vaccination.

Do I have a permanent protection after vaccination? The antibody titers and likely the cellular immune response is significantly reduced in patients with kidney diseases, and titers are reducing at a fast pace under ongoing immunosuppression. A booster dose should be considered, especially taking into consideration the evolvement of virus variants and their impact on vaccine efficacy.

After the first series of vaccination, no or only a marginal amount of antibodies were detectable. Are there strategies to improve vaccine response? Many countries recommend the application of a third dose for vulnerable patient cohorts, especially because of a weakened response and their risk to develop a severe disease course of COVID-19. Prospective clinical trials are ongoing to test the ideal strategy to improve vaccine response in these cohorts.

Publication History

Article published online:
22 September 2021

© 2021. Thieme. All rights reserved.

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• Literatur

• 1 Windpessl M, Bruchfeld A, Anders HJ. et al. COVID-19 vaccines and kidney disease. Nat Rev Nephrol 2021; 17: 291-293 DOI: 10.1038/s41581-021-00406-6.
  CrossrefPubMedGoogle Scholar
• 2 Heine GH, Becker SL, Scheuer AL. et al. [SARS-CoV-2 vaccines – what the nephrologist should know]. Dtsch Med Wochenschr 2021; 146 (07) 466-470 DOI: 10.1055/a-1375-4471.
  Article in Thieme ConnectPubMedGoogle Scholar
• 3 Sadoff J, Gray G, Vandebosch A. et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against COVID-19. N Engl J Med 2021; 384: 2187-2201 DOI: 10.1056/NEJMoa2101544.
  CrossrefPubMedGoogle Scholar
• 4 Polack FP, Thomas SJ, Kitchin N. et al. Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. N Engl J Med 2020; 383: 2603-2615 DOI: 10.1056/NEJMoa2034577.
  CrossrefPubMedGoogle Scholar
• 5 Kronbichler A, Anders HJ, Fernandez-Juárez GM. et al. Recommendations for the use of COVID-19 vaccines in patients with immune-mediated kidney diseases. Nephrol Dial Transplant 2021; DOI: 10.1093/ndt/gfab064.
  CrossrefPubMedGoogle Scholar
• 6 Carr EJ, Kronbichler A, Graham-Brown M. et al. Systematic Review of Early Immune Response to SARS-CoV-2 Vaccination Among Patients with Chronic Kidney Disease. Kidney Int Rep 2021; DOI: 10.1016/j.ekir.2021.06.027.
  CrossrefPubMedGoogle Scholar
• 7 Kaiser RA, Haller MC, Apfalter P. et al. Comparison of BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) SARS-CoV-2 mRNA vaccine immunogenicity in dialysis patients. Kidney Int 2021; 100 (03) 697-698
  CrossrefPubMedGoogle Scholar
• 8 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 (21) 2204-2206 DOI: 10.1001/jama.2021.7489.
  CrossrefPubMedGoogle Scholar
• 9 Connolly C, Koenig D, Ravi S. et al. Correspondence on “SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response” by Bonelli et al. Ann Rheum Dis 2021; DOI: 10.1136/annrheumdis-2021-220972.
  CrossrefPubMedGoogle Scholar
• 10 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 DOI: 10.1038/s41591-021-01377-8.
  CrossrefPubMedGoogle Scholar
• 11 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; DOI: 10.1111/ajt.16701.
  CrossrefPubMedGoogle Scholar
• 12 Herrera S, Colmenero J, Pascal M. et al. Cellular and humoral immune response after mRNA-1273 SARS-CoV-2 vaccine in liver and heart transplant recipients. Am J Transplant 2021; DOI: 10.1111/ajt.16768.
  CrossrefPubMedGoogle Scholar
• 13 Broseta JJ, Rodríguez-Espinosa D, Rodríguez N. et al. Humoral and Cellular Responses to mRNA-1273 and BNT162b2 SARS-CoV-2 Vaccines Administered to Hemodialysis Patients. Am J Kidney Dis 2021; DOI: 10.1053/j.ajkd.2021.06.002.
  CrossrefPubMedGoogle Scholar
• 14 Prendecki M, Thomson T, Clarke CL. et al. Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines. medRxiv preprint DOI: 10.1101/2021.07.09.21260192.
  CrossrefPubMedGoogle Scholar
• 15 Clarke CL, Martin P, Gleeson S. et al. Comparison of immunogenicity between BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines in a large haemodialysis population. medRxiv preprint DOI: 10.1101/2021.07.09.21260089.
  CrossrefPubMedGoogle Scholar
• 16 Labriola L, Scohy A, Seghers F. et al. A Longitudinal, 3-Month Serologic Assessment of SARS-CoV-2 Infections in a Belgian Hemodialysis Facility. Clin J Am Soc Nephrol 2021; 16: 613-614 DOI: 10.2215/CJN.12490720.
  CrossrefPubMedGoogle Scholar
• 17 Cohen DE, Sibbel S, Marlowe G. et al. Antibody Status, Disease History, and Incidence of SARS-CoV-2 Infection Among Patients on Chronic Dialysis. J Am Soc Nephrol 2021; 32: 1880-1886 DOI: 10.1681/ASN.2021030387.
  CrossrefPubMedGoogle Scholar
• 18 Benotmane I, Gautier-Vargas G, Gallais F. et al. Strong antibody response after a first dose of a SARS-CoV-2 mRNA-based vaccine in kidney transplant recipients with a previous history of COVID-19. Am J Transplant 2021; DOI: 10.1111/ajt.16764.
  CrossrefPubMedGoogle Scholar
• 19 Blazquez-Navarro A, Safi L, Meister TL. et al. Superior cellular and humoral immunity towards SARS-CoV-2 reference and alpha and beta VOC strains in COVID-19 convalescent as compared to the prime boost BNT162b2 vaccinated dialysis patients. Kidney Int 2021; DOI: 10.1016/j.kint.2021.07.006.
  CrossrefPubMedGoogle Scholar
• 20 Kant S, Kronbichler A, Salas A. et al. Timing of COVID-19 Vaccine in the Setting of Anti-CD20 Therapy: A Primer for Nephrologists. Kidney Int Rep 2021; 6 (05) 1197-1199 DOI: 10.1016/j.ekir.2021.03.876.
  CrossrefPubMedGoogle Scholar
• 21 Del Bello A, Marion O, Delas A. et al. Acute rejection after anti-SARS-CoV-2 mRNA vaccination in a patient who underwent a kidney transplant. Kidney Int 2021; 100 (01) 238-239 DOI: 10.1016/j.kint.2021.04.025.
  CrossrefPubMedGoogle Scholar
• 22 Doria-Rose N, Suthar MS, Makowski M. et al. Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for COVID-19. N Engl J Med 2021; 384 (23) 2259-2261 DOI: 10.1056/NEJMc2103916.
  CrossrefPubMedGoogle Scholar
• 23 Caillard S, Chavarot N, Bertrand D. et al. Occurrence of severe COVID-19 in vaccinated transplant patients. Kidney Int 2021; DOI: 10.1016/j.kint.2021.05.011.
  CrossrefPubMedGoogle Scholar
• 24 Ravanan R, Mumford L, Ushiro-Lumb I. et al. Two Doses of SARS-CoV-2 Vaccines Reduce Risk of Death Due to COVID-19 in Solid Organ Transplant Recipients: Preliminary Outcomes From a UK Registry Linkage Analysis. Transplantation 2021; DOI: 10.1097/TP.0000000000003908.
  CrossrefPubMedGoogle Scholar
• 25 Wall EC, Wu M, Harvey R. et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet 2021; 397: 2331-2333 DOI: 10.1016/S0140-6737(21)01290-3.
  CrossrefPubMedGoogle Scholar
• 26 Lucas C, Vogels CBF, Yildirim I. et al. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals. medRxiv preprint DOI: 10.1101/2021.07.14.21260307.
  CrossrefPubMedGoogle Scholar
• 27 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; DOI: 10.1056/NEJMc2108861.
  CrossrefPubMedGoogle Scholar
• 28 Del Bello A, Abravanel F, Marion O. et al. Efficiency of a boost with a third dose of anti-SARS-CoV-2 messenger RNA-based vaccines in solid organ transplant recipients. Am J Transplant 2021; DOI: 10.1111/ajt.16775.
  CrossrefPubMedGoogle Scholar
• 29 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; DOI: 10.7326/L21-0282.
  CrossrefPubMedGoogle Scholar
• 30 Schmidt T, Klemis V, Schub D. et al. Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination. Nat Med 2021; DOI: 10.1038/s41591-021-01464-w.
  CrossrefPubMedGoogle Scholar