SARS-COV-2 NEUTRALIZING ANTIBODIES IN PATIENTS ON HEMODIALYSIS AFTER VACCINATION

ABSTRACT

BACKGROUND: Patients on hemodialysis (HD) are at high risk of a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), and humoral and cellular response data in these patients are limited. SARS-CoV-2 has four major structural proteins spike (S), membrane, envelope and nucleocapsid (N) proteins. The S protein consists of the S1 and S2 subunits, which mediate cell surface binding via the receptor-binding domain, and induce viral-host cell membrane fusion, respectively. Approximately, 90% of the SARS-CoV-2-specific neutralizing antibodies (nAbs) target the highly immunogenic receptor-binding domain, but there is little evidence of nAbs targeting other viral structural proteins, such as the N protein. Speer et al. reported reduced Ab responses to the first and second doses of the mRNA vaccine, BNT162b2 (BioNTech), in patients on long-term HD. The majority (82%) of patients developed nAbs after the second dose, but at lower levels than healthy controls (HCs) [1]. Since data on the efficacy of COVID-19 vaccination in patients on HD are limited, we investigated the SARS-CoV-2 nAbs in Japanese patients on HD. METHOD: Forty-two patients (24 males and 18 females) on HD for an average of 4.5 years (0-21), with a mean age of 68 years (28-92), who received two doses of the mRNA vaccine, BNT162b2, between May 1 and 30 November 2021 were included. In addition, 10 HCs (6 males and 4 females with mean age of 55 (26-75) and 41 (28-63) years, respectively) with normal renal function who received two doses of the mRNA vaccine BNT162b2 in the same period were tested for SARS-CoV-2 nAbs at 4, 8, 12, 16 and 20 weeks (W) after vaccination. We measured SARS-CoV-2 Abs in human plasma qualitatively with a fully automated Cobas e801 analyzer, an Elecsys ® Anti-SARS-CoV-2 electrochemiluminescence immunoassay, and an Elecsys ® Anti-SARS-CoV-2 S RUO electrochemiluminescence immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) according to the manufacturer's instructions. RESULTS: Approximately, 97.6% (41/42) of patients on HD tested positive for SARSCoV-2 nAbs. The mean titer of SARS-CoV-2 nAbs after BNT162b2 vaccination in all individuals was 490.1 (0.4-5116) U/mL. The mean titers of SARS-CoV-2 nAbs after BNT162b2 vaccination in patients on HD aged between 56-92 years and 28-53 years were 266.7 (0.4-1131) U/mL and 1320.4 (44.8-5116) U/mL, respectively. The levels of nAbs were lower in the older group than in the younger group. Patients on HD are associated with premature aging of the immune systems. Progressive immunosenescence may be associated with reduced T cell activity and humoral response, potentially leading to reduced vaccine protection. During the follow-up period, Abs against N protein were not detected in all individuals. Over 90% of patients on HD wore face masks, washed their hands and maintained a 2 m social distance in the dialysis facilities. Almost all patients avoided the three Cs (closed spaces with poor ventilation, crowded places with nearby people and close-contact settings, such as close-range conversations). In contrast, the mean SARS-CoV-2 nAb titers in the older (55-73 years) HCs were 1006, 643, 520, 464 and 390 U/mL at 4, 8, 12, 16 and 20 W post-vaccination. Contrastingly, the mean SARS-CoV-2 nAb titers in the younger (26-45 years) HCs were 2685, 2032, 1731, 1609 and 1527 U/mL at 4, 8, 12, 16 and 20 W post-vaccination. The nAb levels decreased gradually and were lower in the older group than in the younger group. CONCLUSION: Japanese patients on HD had SARS-CoV-2 neutralizing capacities after BNT162b2 vaccination. The majority (97.6%) developed nAb after the second dose. The levels of neutralizing antibodies were lower in the older group than in the younger group.