nAb, neutralizing antibody; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus?2
nAb, neutralizing antibody; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus?2. Where possible, we obtained repeat sera and measured S1, N, and neutralizing antibodies from seroconverted patients at a median of 93 days from baseline sampling. Results All patients with ESKD with reverse-transcriptase polymerase chain reaction (RT-PCR)Cconfirmed 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 Setiptiline 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: ESKD, hemodialysis, antibody, COVID-19, SARS-CoV-2, neutralization assay Graphical abstract Open in a separate window See Commentary on Page 1761 Patients with ESKD represent an extremely vulnerable group with a disproportionate number of recognized risk factors for adverse outcomes after SARS-CoV-2 infection.1, 2, 3 Data from the UK Renal Registry have revealed that by the end of the first wave of the pandemic, 23% of patients receiving incenter hemodialysis (ICHD) and infected with SARS-CoV-2 have died.4 Dialysis units are recognized as potential centers for the rapid spread of SARS-CoV-2,5,6 and some of the key questions pertaining to infection in patients with ESKD, in particular those receiving ICHD as they comprise more than 70% of PTEN1 the incident renal transplant population, include quantifying the frequency of asymptomatic infection and determining whether seroconversion is protective against further infection.7,8 Moreover, many of the commercially available assays do not give information on comparable antibody titer, the variety of different antigenic targets that antiCSARS-CoV-2 antibodies (nucleocapsid and spike) are raised to,9,10 or their viral neutralizing ability, which is considered the gold standard for measuring a functional antibody that can inhibit SARS-CoV-2 infection.11, 12, 13, 14, 15, 16 Allied to an overall increased risk of infections, patients with ESKD have impaired cell-mediated and humoral immune responses, leading to lower seroconversion rates and quicker decline of?antibody levels as compared with healthy subjects.17, 18, 19, 20, 21 Whether patients on hemodialysis mount an effective nAb response against SARS-CoV-2 is currently unknown. A more detailed evaluation of the humoral response to SARS-CoV-2 in ESKD is thus required. Here, we set out to quantify IgG antibody levels to spike S1 subunit (S1) and nucleocapsid (N) proteins of SARS-CoV-2 and evaluate how well these responses correlate with nAb activity.22, 23, 24 Determining the neutralizing ability of SARS-CoV-2 spike antibodies is critical to understanding protection from reinfection14,15,25 in patients awaiting transplantation and as a consequence likely to receive immunosuppressiona significant Setiptiline risk factor for poor prognosis in SARS-CoV-2 infection.3 Methods Patient Selection A total of 217 patients affiliated with Setiptiline The Royal Free London NHS Trust (London, UK) and, as of 30 May 2020, listed on the National NHS Blood and Transplant waiting list for renal transplantation were included. Clinical and routine pathology data were obtained from electronic and dialysis records. The study was approved by The Royal Free London NHS Foundation TrustUCL Biobank Honest Review Committee (RFL B-ERC; research NC.2018.010). Individuals were adopted up until 15 January 2021. A total of 57 individuals (26 seropositive and 31 seronegative) experienced received a kidney transplant by this day. Data Collection Demographic info, clinical presentations, chest computed tomography results, laboratory tests, and treatment and end result data were collected from patient medical records. COVID-19 severity was classified as previously explained by Seow checks, and nonparametric data were compared using the MannCWhitney test. The Fisher exact checks or chi-square checks were utilized for proportional assessments..