Serological responses and clinical outcomes following a three‐dose primary COVID‐19 vaccine schedule in kidney transplant recipients and people on dialysis

Author:

Tharmaraj Dhakshayini12ORCID,Boo Irene3,O'Hara Jessie4,Sun Shir35,Polkinghorne Kevan R126,Dendle Claire27,Turner Stephen J4ORCID,van Zelm Menno C58,Drummer Heidi E349,Khoury Gabriela34,Mulley William R12

Affiliation:

1. Department of Nephrology Monash Health Clayton VIC Australia

2. Department of Medicine, Centre for Inflammatory Diseases Monash University Melbourne VIC Australia

3. Burnet Institute Melbourne VIC Australia

4. Department of Microbiology, Monash Biomedicine Discovery Institute Monash University Melbourne VIC Australia

5. Department of Immunology, School of Translational Medicine Monash University and Alfred Health Melbourne VIC Australia

6. Department of Epidemiology and Preventive Medicine Monash University Melbourne VIC Australia

7. Monash Infectious Diseases Monash Health Clayton VIC Australia

8. Department of Immunology, Erasmus MC University Medical Center Rotterdam The Netherlands

9. Department of Microbiology and Immunology University of Melbourne Melbourne Victoria Australia

Abstract

AbstractObjectivesDespite vaccination strategies, people with chronic kidney disease, particularly kidney transplant recipients (KTRs), remained at high risk of poor COVID‐19 outcomes. We assessed serological responses to the three‐dose COVID‐19 vaccine schedule in KTRs and people on dialysis, as well as seroresponse predictors and the relationship between responses and breakthrough infection.MethodsPlasma from 30 KTRs and 17 people receiving dialysis was tested for anti‐Spike receptor binding domain (RBD) IgG and neutralising antibodies (NAb) to the ancestral and Omicron BA.2 variant after Doses 2 and 3 of vaccination.ResultsAfter three doses, KTRs achieved lower anti‐Spike RBD IgG levels (P < 0.001) and NAb titres than people receiving dialysis (P = 0.002). Seropositive cross‐reactive Omicron neutralisation levels were achieved in 11/27 (40.7%) KTRs and 11/14 (78.6%) dialysis recipients. ChAdOx1/viral‐vector vaccine type, higher mycophenolate dose (> 1 g per day) and lower absolute B‐cell counts predicted poor serological responses in KTRs. ChAdOx‐1 vaccine type and higher monocyte counts were negative predictors in dialysis recipients. Among ancestral NAb seroresponders, higher NAb levels positively correlated with higher Omicron neutralisation (R = 0.9, P < 0.001). More KTRs contracted SARS‐CoV‐2 infection (14/30; 47%) than dialysis recipients (5/17; 29%) and had more severe disease. Those with breakthrough infections had significantly lower median interdose incremental change in anti‐Spike RBD IgG and ancestral NAb titres.ConclusionSerological responses to COVID‐19 vaccines in KTRs lag behind their dialysis counterparts. KTRs remained at high risk of breakthrough infection after their primary vaccination schedule underlining their need for booster doses, strict infection prevention measures and close surveillance.

Publisher

Wiley

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