Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection

Abstract

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.

Keywords: COVID-19; SARS-CoV-2; hemodialysis; serology.

Graphical abstract

Figure 1

Patient cohort flow diagram by nucleocapsid antibody (anti-NP) and receptor-binding domain antibody (anti-RBD) status after the first wave of infection. ICHD, in-center hemodialysis; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2

Comparison of nucleocapsid protein (anti-NP) and receptor-binding domain (anti-RBD) antibody levels at time 0 and 6 months. (a) Anti-NP antibody. Plots show summary and individual patient data. Forty of 111 patients with detectable anti-NP at time 0 (36.0%) became anti-NP− at 6 months. For those retaining antibodies, the anti-NP index (S/C) was significantly higher at time 0 than at 6 months post-testing, with a median S/C of 6.9 (interquartile range [IQR] 5.2–8.2) and 2.3 (IQR 0.9–4.3), respectively (P < 0.0001). (b) Anti-RBD antibody. Plots show summary and individual patient data. Ninety-seven of 111 patients with anti-RBD at time 0 (87.4%) retained their antibodies at 6 months. For those retaining antibodies, the anti-RBD index (S/CO) was significantly higher at time 0 than at 6 months post-testing, with a median S/CO of 23.9 (IQR 23.4–26.1) and 23.4 (IQR 8.9–24.1), respectively (∗∗∗∗P < 0.0001).

Figure 3

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)–positive free survival at 60 days after the first serological testby antibody status. (a) Nucleocapsid (anti-NP) antibody. From >60 days after initial serological testing, anti-NP+ patients were at a significantly lower risk of being diagnosed with SARS-CoV-2 than anti-NP− patients (log-rank, P = 0.0005). (b) Receptor-binding domain (anti-RBD) antibody. From >60 days after initial serological testing, anti-RBD+ patients were also at a lower risk of being diagnosed with SARS-CoV-2 by PCR testing compared with anti-RBD− patients (log-rank, P = 0.0051).