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

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.

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"

Objectives:
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.