Neutralizing Antibody Responses After SARS-CoV-2 Infection in End-Stage Kidney Disease and Protection Against Reinfection

Luke Muir; Aneesa Jaffer; Chloe Rees-Spear; Vignesh Gopalan; Fernando Y Chang; Raymond Fernando; Gintare Vaitkute; Chloe Roustan; Annachiara Rosa; Christopher Earl; Gayathri K Rajakaruna; Peter Cherepanov; Alan Salama; Laura E McCoy; Reza Motallebzadeh

doi:10.1016/j.ekir.2021.03.902

Neutralizing Antibody Responses After SARS-CoV-2 Infection in End-Stage Kidney Disease and Protection Against Reinfection

Kidney Int Rep. 2021 Jul;6(7):1799-1809. doi: 10.1016/j.ekir.2021.03.902. Epub 2021 Apr 28.

Authors

Luke Muir^{1

2}, Aneesa Jaffer³, Chloe Rees-Spear^{1

2}, Vignesh Gopalan³, Fernando Y Chang⁴, Raymond Fernando³, Gintare Vaitkute⁴, Chloe Roustan⁵, Annachiara Rosa⁵, Christopher Earl⁵, Gayathri K Rajakaruna⁶, Peter Cherepanov⁵, Alan Salama^{3

6}, Laura E McCoy^{1

2}, Reza Motallebzadeh^{1

3

4

6}

Affiliations

¹ UCL Institute of Immunity & Transplantation, University College London, London, UK.
² UCL Division of Infection & Immunity, University College London, London, UK.
³ Department of Nephrology & Transplantation, Royal Free London NHS Trust, London, UK.
⁴ Research Department of Surgical Biotechnology, UCL Division of Surgery and Interventional Science, University College London, London, UK.
⁵ The Francis Crick Institute, London, UK.
⁶ Centre for Transplantation, Department of Renal Medicine, University College London, London, UK.

Abstract

Introduction: Patients with end-stage kidney disease (ESKD) represent a vulnerable group with multiple risk factors that are associated with poor outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite established susceptibility to infectious complications and the importance of humoral immunity in protection against SARS-CoV-2, few studies have investigated the humoral immune response to SARS-CoV-2 within this population. Here, we evaluate the seroprevalence of SARS-CoV-2 in patients awaiting renal transplantation and determine whether seroconverted patients with ESKD have durable and functional neutralizing activity against SARS-CoV-2.

Methods: Serum samples were obtained from 164 patients with ESKD by August 2020. Humoral immune responses were evaluated by SARS-CoV-2 spike S1 subunit and nucleoprotein semiquantitative enzyme-linked immunosorbent assay (ELISA) and SARS-CoV-2 spike pseudotype neutralization assay.

Results: All patients with ESKD with reverse-transcriptase polymerase chain reaction (RT-PCR)-confirmed infection (n = 17) except for 1 individual seroconverted against SARS-CoV-2. Overall seroprevalence (anti-S1 and/or anti-N IgG) was 36% and was higher in patients on hemodialysis (44.2%). A total of 35.6% of individuals who seroconverted were asymptomatic. Seroconversion in the absence of a neutralizing antibody (nAb) titer was observed in 12 patients, all of whom were asymptomatic. Repeat measurements at a median of 93 days from baseline sampling revealed that most individuals retained detectable responses although a significant drop in S1, N and nAb titers was observed.

Conclusion: Patients with ESKD, including those who develop asymptomatic disease, routinely seroconvert and produce detectable nAb titers against SARS-CoV-2. Although IgG levels wane over time, the neutralizing antibodies remain detectable in most patients, suggesting some level of protection is likely maintained, particularly in those who originally develop stronger responses.

Keywords: COVID-19; ESKD; SARS-CoV-2; antibody; hemodialysis; neutralization assay.

Grants and funding

MR/R008698/1/MRC_/Medical Research Council/United Kingdom