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American Journal of Transplantation ; 21(SUPPL 4):316, 2021.
Article in English | EMBASE | ID: covidwho-1494455


Purpose: Patients with end-stage kidney disease (ESKD) represent an extremely vulnerable group with many risk factors for adverse outcomes following SARSCoV- 2 infection. Key questions pertaining to ESKD patients awaiting transplantation include quantifying the rates of symptomatic & asymptomatic infection and determining if seroconverted patients have functional neutralising activity against SARS-CoV-2. The study of the immunological characteristics of COVID-19 in ESKD patients may help the design of an effective vaccination strategy against SARS-CoV-2 for potential transplant recipients. Methods: Serum samples were analysed by direct ELISA to detect anti-SARS-CoV-2 IgG antibodies using a recombinant Spike S11-530 subunit and Nucleocapsid protein (NP). Recombinant human anti-SARS-CoV-2 mAbs that bind to spike RBD and NP were used as positive controls. Neutralization potency against SARS-CoV-2 was measured using HIV-1 luciferase-based pseudotype assays. Titres of neutralising antibodies were calculated as 50% inhibitory dose (ID50), expressed as the highest dilution of plasma which resulted in 50% reduction of luciferase luminescence compared with controls. Results: 217 patients were on our wait-list as of May 2020 (115 receiving in-centre haemodialysis [ICHD], 41 on peritoneal dialysis and 61 pre-dialysis). 164 serum samples, of which 76% were obtained by June 2020 and coincided with the first peak of the pandemic in UK, were analysed. The observed seroprevalence of SARS-CoV-2 antibodies was 36% (95% CI 32-46). Seroconverted patients were more frail (median Clinical Frailty Scale score 3 [IQR: 3-4] vs 3 [IQR: 2-3];p=0.02), mostly from BAME background (76.3% vs 52.4%, p=0.04), had higher prevalence of diabetes (27.1% vs 12.4%;p=0.02), and received ICHD (84.7% vs 60%;p=0.006). Levels of anti-S1 and anti-NP SARS-CoV-2 IgG strongly correlated with ID50 (r=0.58, p<0.0001 and r=0.41, p=0.004, respectively). Peak CRP levels were correlated with ID50 (r=0.30;p=0.05). There were significant declines of S1 and NP antibody titres as well as neutralising activity by a median of 90 days. Conclusions: Analysis of SARS-CoV-2 antibodies and neutralising activity suggest robust functional responses are produced in infected ESKD patients, but titres wane significantly by 3 months. The level of functional immunity to SARS-CoV-2 in patients with ESKD may be used to risk stratify patients on national waiting-lists for renal transplantation and will help evaluate the efficacy of vaccination schedules in wait-listed patients once this becomes available.