Determining functional immunity after SARS-CoV-2 vaccination or natural infection in haemodialysis patients at high-risk of COVID-19

Lead Research Organisation: University of Birmingham
Department Name: Institute of Applied Health Research


Patients with multiple diseases are more likely to die from Covid-19 infection. Patients with End-Stage Kidney Disorder (ESKD) are some of the worst affected, being 45 times more likely to die. These patients cannot shield due to their treatment, haemodialysis, which requires in person treatment at a hospital, increasing the patients risk of infection. ESKD patients can create antibodies, a type of protein produced by the body to fight infection. This suggests that a Covid-19 vaccine, which stimulates production of antibodies, would help to protect the patients; however, it is not known how effective the antibodies would be at protecting ESKD patients.

To find out if the antibodies help to protect ESKD patients, this research will look at:
1. The characteristics of the patients' antibodies in response to natural Covid infection and Covid-19 vaccine.
2. To find out how effective the patients' antibodies are at different time-points, after infection or vaccination.
3. To find out how resistant to infection different cells from patients are if antibodies are present or not.

These studies will help us to understand if the created antibodies help to protect ESKD patients against Covid; this will allow us to make better choices for at risk patients and their treatment, shielding and the benefits of vaccination to them.

Technical Summary

Patients with comorbidities have a higher likelihood of death from SARS-CoV-2 infection. Amongst those worst affected are patients with end-stage kidney disease (ESKD), who are 45 times more likely to die than matched populations. Tragically, ESKD patients requiring haemodialysis (ESKDHD) cannot shield and face unavoidable risks of infection through the necessity to attend hospital for treatment. Despite their intrinsic susceptibility to COVID-19, ESKD patients can generate antiviral antibodies and thus may respond to vaccination. Nevertheless, it is unknown if after natural infection or vaccination: i) anti-viral serum and mucosal (salivary) antibodies are induced and maintained comparably to matched controls; ii) antibodies are functional and neutralise infection/promote opsonisation; iii) Whether host immune cells (neutrophils/macrophages) +/- antibody control virus infection.

To answer these unknowns we will address the following hypothesis and objectives:

Hypothesis "Antibodies and immune cells from vaccinated or naturally-infected ESKD-HD patients and matched controls are equally effective at neutralizing SARS-CoV-2 infection"

1. To identify the nature, magnitude and longevity of the systemic and mucosal B cell response to SARS-CoV-2 in naturally-infected or vaccinated ESKD-HD patients
2. To determine the functionality and neutralising capacity of serum and salivary antibodies generated by ESKD-HD patients at different times post-vaccination/infection
3. To determine the capacity of different immune/non-immune cells from ESKD-HD patients to resist infection in the presence or absence of antibodies

From these studies, we will understand if virus-specific antibodies are friends or foes in these clinically extremely vulnerable patients and inform our approach to treatment, shielding and the benefits of vaccination.
Description 1. We have shown that patients with end-stage renal failure treated by haemodialysis make long-lived antibodies to SARS-CoV-2 following natural infection. Responses are maintained for at least 200 days in most, but levels do decline. Patients with sub-clinical disease develop lower titres of antibody. Antibodies correlated with a reduced risk of infection during wave 2 of the pandemic (JASN 2021 Banham et al).

2. Testing a subset of HD patients who received two vaccinations revealed concerns over the level of neutralising antibodies to the delta VOC in HD patients vaccinated with ChAdOx1, but not BNT162b2 (Lancet 2021 Carr et al). This was fed into JCVI.

3. Our combined antibody and antigen (PCR) testing of HD patients shows that two doses of SARS-CoV-2 vaccine reduces susceptibility to, but not severity of SARS-CoV-2 infection in haemodialysis patients .
Exploitation Route By understanding the immune response and reduced efficacy of the COVID 19 vaccines in this highly vulnerable population will allow development of improved vaccines to COVID 19 and other viruses such as flu, another virus that is associated with high morbidity/mortality and has a reduced response to vaccination in this population
Sectors Healthcare

Pharmaceuticals and Medical Biotechnology

Description Contributed to advice that haemodialysis patients should receive a 3rd primary and booster dose of the COVID 19 vaccine distributed by the UK Kidney Association
First Year Of Impact 2021
Sector Healthcare
Impact Types Policy & public services

Description Haemodialysis COVID-19 consortium 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of samples and patient data to explore immune response to COVID vaccination in patients treated by haemodialysis
Collaborator Contribution measurement of neutralisation antibodies following COVID 19 vaccination which predict break through infection in our vulnerable population
Impact publication doi: 10.1016/S0140-6736(21)01854- manuscript submitted to J Infect - breakthrough COVID Infections in patients treated by haemodialysis multi-disciplinary research - clinical immunologists, nephrologists, basic scientists, oncologist
Start Year 2021
Description UKKW research presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact presentation of findings of research to UKKW
Year(s) Of Engagement Activity 2021
Description webinar UKKA-KRUK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact knowledge transfer to renal community regarding important outcomes of vaccination studies in all renal communities
Year(s) Of Engagement Activity 2022