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.
ABSTRACT
BACKGROUND AND AIMS: Strategies to minimize the risk of transmission of coronavirus disease 2019 (COVID-19) infection in hemodialysis (HD) patients have been rapidly implemented worldwide (Nature 16: 311, 2020). Serological testing of 356 HD patients revealed that 129 (36.2%) patients were positive for SARS-CoV-2 antibodies. Out of these 129 patients, 52 (40.3%) patients were asymptomatic (JASN 31:1969, 2020). In this study, we investigated the seroprevalence of SARS-CoV-2 antibodies in HD patients who were managed per Japanese Society for Dialysis-Therapy guidelines in the context of COVID-19. METHOD: Study (1): A total of, 55 patients that underwent HD (41 males, 14 females;mean age: 66.3612.8 years, HD duration: 72.2±68.4 months) between August 1 and December 14, 2020, were included. We measured SARS-CoV-2 antibodies with a fully automated cobas e801 analyzer using an Elecsys® Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Roche Diagnostics) to qualitatively detect SARS-CoV-2 antibodies in human plasma. The Elecsys® assay uses a modified doubleantigen sandwich immunoassay with recombinant nucleocapsid protein (N), which is geared towards the detection of late, mature, high-affinity antibodies independent of the subclass. Study (2): We tested the plasma of 8,982 adult with normal renal function for SARS-CoV-2 antibodies between July 1 and November 18, 2020. RESULTS: Study (1): Using serological testing, only 2 out of 55 (3.64%) HD patients tested positive for SARS-CoV-2 antibodies. In total 54 patients were asymptomatic during the study period and did not have a polymerase chain reaction (PCR) test. Only 1 out of the 54 (1.85%) patients that were asymptomatic had SARS-CoV-2 antibodies. Case 1 was an 89-year-old, male who had undergone HD for 53 months because of end stage kidney disease (ESKD) secondary to diabetic nephropathy. His blood type was O Rh (+). This patient tested positive for SARS-CoV-2 antibodies on August 11, 2020. Serological testing showed that this patient had an asymptomatic disease. Case 2 was a 74-year-old, male that had undergone HD for 62 months due to ESKD secondary to diabetic nephropathy. He was hospitalized because of bradycardia-tachycardia syndrome on November 14, 2020. On that day, his PCR test was negative. He underwent surgery to insert a cardiac pacemaker on November 18, and had a fever (37.7°C) on November 24. A chest CT scan revealed that he had bilateral lung pneumonia. On that day, his PCR test was positive. Blood tests showed that his white blood cell count was 4300/μL (lymphocyte 30.4%), and C-reactive protein (CRP) levels was 2.8 mg/dL. He was not treated with antiviral medication, the PCR test was repeated and was positive on December 4,7, and 9. However, his PCR test was negative on December 13. This patient tested positive for SARS-CoV-2 antibodies on December 14. He recovered from a COVID-19 infection 21 days after the onset of the disease. Study (2): Using serological testing, 47 out of 8,982 (0.52%) adults tested positive for SARSCoV-2 antibodies. In Japan, the population of Kanagawa prefecture is 9,216,009. The number of PCR-confirmed patients with COVID-19 infection was 13,340 (0.14%) on December 6, 2020. The estimated number of asymptomatic SARS-CoV-2 infection was 47,923 (0.52%). The total estimated number of patients with COVID-19 infection was 61,263. In study 1, more than 90% of HD patients wear face masks, wash their hands, and maintain social distance of 2 m in dialysis facilities. Almost all patients avoided the three Cs (closed spaces with poor ventilation, crowded places with nearby people, close-contact settings, such as close-range conversations). CONCLUSION: We found that Japanese patients on HD had a lower prevalence of SARS-CoV-2 antibodies compared to those in the United Kingdom. Serological testing identified HD patients with asymptomatic disease. Avoiding the 'three Cs' is very important in minimizing the risk of COVID-19 among HD patients.