SEROCONVERSION FOLLOWING COVID-19 VACCINATION IN DIALYSIS PATIENTS [COVID-19]
Research type
Research Study
Full title
PHENOTYPING SEROCONVERSION FOLLOWING VACCINATION AGAINST COVID-19 IN PATIENTS ON HAEMODIALYSIS
IRAS ID
292716
Contact name
Matthew PM Graham-Brown
Contact email
Sponsor organisation
University of Leicester
Duration of Study in the UK
0 years, 10 months, 31 days
Research summary
Patients with end stage kidney disease (ESKD) on haemodialysis are more likely to suffer poorer outcomes following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is likely to be because these patients have higher levels of co-morbid diseases (other diseases on top of the kidney disease) and they are relatively immunosuppressed due to the effects of advanced kidney disease. The response against common viral vaccination is known to be blunted in patients with ESKD and there are data to suggest seroconversion (production of detectable antibodies) following infection with COVID-19 is blunted in patients with kidney disease. A successful programme of vaccination will undoubtedly improve outcomes for patients on haemodialysis, but vaccine testing programmes have not included patients who with ESKD. Whilst initial press-coverage of the efficacy of vaccines which are available for use is promising, they are untested in patients on haemodialysis who are known to be relatively immunosuppressed as a result of their kidney disease and as such the efficacy for this patient group is not known.
This study will assess the IgG antibody response to vaccination for COVID-19 in 100 patients on haemodialysis compared to 50 healthy volunteers. Antibody testing will be conducted at 1 month post first vaccination dose and 1 month and 6 months post second vaccination dose. This will give crucial information as to the efficacy of the vaccine and inform possible requirements for re-vaccination.Lay summary of study results: 1: The presence or absence of antibodies 28 days after the first vaccine dose in the data we present is not synonymous with protection or absence of protection from COVID-19. Rather, these data should be viewed as a call to arms to all who care for these patients to coordinate the collection and standardized analysis of seroconversion following vaccination internationally to understand the immune response and how this relates to subsequent infection rates and outcomes for these patients. These data are essential to inform current and future vaccination programs to protect patients receiving hemodialysis who have had to endure the worst of the pandemic.
2: The delivery of any approved vaccine will probably mitigate disease and death, but the optimal strategy for haemodialysis patients who are yet to start a vaccination course remains to be determined. Our data suggest that two doses of micro-RNA vaccine or a boosting strategy are likely to offer the broadest variant of concern protection. The United Kingdoms Joint Committee on Vaccination and Immunisation has announced third doses, in principle, for many vulnerable groups. The precise start date for this programme, which vaccines are used, and the ordering of the groups is under review. Internationally, most countries with pre-existing vaccination strategies for haemodialysis patients, have used two doses of micro-RNA vaccines, and results of three studies testing a third dose of one in 132 haemodialysis patients in France suggest further augmentation of antibody responses. We suggest that in-centre haemodialysis patients should be prioritised for a third dose, particularly AstraZenica recipients who have not already survived infection.
3: There are several implications of these data. First, the deployment of third doses in the UK took about 8 weeks between eligibility announcements for third or booster doses and their receipt in this highly vulnerable patient group. This contrasts with their very rapid access to first doses. Second, a lack of a quantifiable response (non-response) after two doses does not predict ongoing non-response to a third dose. We suggest that each further dose reduces this fraction. Some of these non-responders are already eligible for four doses in the UK, as their primary course has already been deemed three doses because of immunosuppression use or comorbidities. Third, adequate antibodies against delta in haemodialysis patients required three doses of vaccine, and this is reflected in the epidemiological data from the delta wave. Finally, omicron neutralisation will require at least three vaccine doses, perhaps four doses, in UK haemodialysis patients, particularly as the kinetics of waning of omicron antibodies are unknown. Together, our data show that the current generation vaccines still have use in clinically extremely vulnerable patient groups and that the number of doses that constitute an appropriate primary course differs between variants: for omicron, three doses in haemodialysis patients might be insufficient.
REC name
West Midlands - Solihull Research Ethics Committee
REC reference
21/WM/0031
Date of REC Opinion
7 Feb 2021
REC opinion
Further Information Favourable Opinion