COVID-19 antibody responses in immunocompromised patients
Research type
Research Study
Full title
SARS CoV-2 antibody responses in immunocompromised patients
IRAS ID
284387
Contact name
Rachel Jones
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust & the University of Cambridge
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
COVID-19 is an international health emergency. There is an urgent unmet need for research which focuses on vulnerable patient groups. Individuals may be vulnerable due to their underlying disease which leads to significant organ damage (for example renal failure, or structural lung damage) or as a consequence of treatments for an underlying condition (immune suppressing medications for those with a transplant, or autoimmune conditions such as vasculitis or systemic lupus erythematosus; or dialysis for individuals with end stage kidney disease). Those individuals who require renal replacement therapy in the form of in centre haemodialysis are particularly at risk; not only are they immunosuppressed as a result of renal failure, but they are obliged to make thrice weekly trips to hospital for life sustaining treatment.
Immunosuppressed patients are currently advised to shield within their homes, whilst efforts are underway to develop a vaccine. This prospect of a widely available vaccine, or the development of herd immunity to offer these vulnerable individuals protection is many months away. However, immunosuppressed patients; either receiving dialysis, or monitoring for renal transplantation or autoimmune disease, require frequent hospital attendances for their ongoing health care thus increasing their vulnerability to COVID-19 infection.
Assays to measure antibodies to Sars CoV-2 are being developed by a number of groups. However, it is vital to understand antibody responses in immunosuppressed populations, both in terms of the magnitude of the response, durability and whether antibody titres correlate with protection against future infection. Studying the renal cohort offers the opportunity to evaluate the effect of various immune suppressing strategies (more B cell targeted approaches in autoimmune disease, or T cell targeted therapies in transplant recipients) in a longitudinal manner, with high quality clinical data key to accurate interpretation of the serological tests.
Lay summary of study results: Study title: COVID-19 antibody responses in immunocompromised patients Who carried out the research?
(Including details of sponsor, funding and any competing interests) The study was sponsored by Cambridge University Hospitals NHS Foundation Trust (CUH) and funded by Addenbrooke’s Charitable Trust and Vasculitis UK.What public involvement there was in the study (how many people, what their relevant lived experience was, and what they did)?
Local patients in the vasculitis and lupus clinic were asked about their willingness to participate in this type of study evaluating immune responses to COVID-19 infection. Positive feedback was received, as these patients recognised themselves as vulnerable and were largely shielding at home at the time of study set-up. In general, patients were very keen to facilitate research into this novel infection which was having an immediate and profound impact on their daily lives. One key concern that emerged, was the potential risk of exposure to virus when attending hospital and so the study was designed to minimise additional visits to hospital.
Was there any patient peer review?
In view of the speed at which the study was set up in the context of a global pandemic, there was not formal patient peer review, but rather informal discuss with patients as highlighted above.
Where and when the study took place. Who participated in the study?
The study commenced in August 2020 initially just in the renal department of Addenbrooke’s Hospital Cambridge. In 2021, it expanded to include three further UK renal centres (Lister, Leicester and Manchester) to expand patient numbers and address the question of magnitude and durability of response to Covid-19 vaccination in the context of immunosuppression.
Why was the research needed?
When the study was set up, there was not information available about antibody responses to natural infection, and then later vaccination in immunocompromised patients. These individuals were considered clinically extremely vulnerable and understanding these aspects of viral protection were essential to inform public health guidance on prevention strategies, including public health measures and booster vaccinations.
What were the main questions studied? What treatments or interventions did the participants take/receive?
Initially patients with immunocompromise (receiving dialysis, with a renal transplant, or with an autoimmune condition receiving immunosuppression) were recruited to have 3 monthly blood samples collected to measure antibodies to Covid-19 to understand whether patients developed a protective response after an infection, and how long these antibodies lasted. When the national vaccination program was launched 4 months into the study, sampling was conducted at regular time intervals to understand the response to initial doses and then booster doses of Covid-19 vaccines. Patients did not receive any treatments as part of the study; all vaccines were given as part of standard of care.
What medical problems (adverse reactions) did the participants have?
All patients in the study were immunocompromised – receiving dialysis, with a renal transplant or with an autoimmune condition necessitating treatment with immunosuppression.What were the results of the study?
Amongst dialysis, kidney transplant and autoimmune populations Covid-19 vaccine antibody responses are reduced compared to healthy controls. A reduced response to vaccination was associated with the drugs rituximab and mycophenolate mofetil, receiving triple immunosuppression and chronic kidney disease stage 4. Vaccine responses increased after the second dose, suggesting low-responder groups should be prioritised for repeated vaccination. Greater antibody responses were observed with the mRNA Pfizer vaccine compared to adenovirus AZ vaccine in dialysis patients suggesting that Pfizer SARS-CoV-2 vaccine should be the preferred vaccine choice in this sub-group. Further analyses in the transplant and autoimmune patients showed that booster vaccines, up to 5 doses, was associated with a reduced risk of breath through infections.
How has this study helped patients and researchers?
When the study was designed, there was no available data on immune responses to Covid-19 infection, and later Covid-19 vaccination in immunocompromised patients. This work has identified patients who are particularly at risk, such as those who received treatment that deplete B cells (rituximab) and supported rationale for booster vaccine doses. It has also raised important questions about how vaccines can be delivered more effectively to immunosuppressed patients and directly led to the design of further small studies testing the re-purposing of existing medications to try to boost responses to vaccines.
Details of any further research planned
Approval has been granted to the VARIED study (Chief investigator Dr Rona Smith; IRAS ID 328759), which brings together samples and clinical data from up to 5000 immunocompromised individuals, including patients recruited to this study to facilitate ongoing research into understanding the immune response to vaccination in immunocompromised individuals. The overarching aim is to more accurately define the immune status of an individual in the context of their underlying health condition and immunosuppressive medication and to be able to risk stratify individuals in a more refined way and tailor approaches to infection prophylaxis both for Covid-19 and other infections.
Where can I learn more about this study?
Please refer to this link which presents initial results of the study - https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Flink.springer.com%252Farticle%252F10.1186%252Fs12882-022-02792-w%2FNBTI%2F2wXDAQ%2FAQ%2Fbe4c77cd-988f-4ca4-8ecb-bfdef1033e9d%2F1%2FtTaV5gzlSI&data=05%7C02%7Cleicestercentral.rec%40hra.nhs.uk%7C406f7b1e8ff946b6ba8908de5e6f3fc2%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639052029061166750%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=Bx3mGvwgZUq9Z%2F25w%2BzA9rdJnwevEBRowNw7BRDYDBI%3D&reserved=0
REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
20/EM/0180
Date of REC Opinion
6 Jul 2020
REC opinion
Favourable Opinion