Dialysis modality, humoral response to vaccine, and SARS-CoV-2 infection risk: Comparative prospective evaluation.

BACKGROUND: COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection. METHODS: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2-3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection. RESULTS: Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2-3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4-13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality. CONCLUSION: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis.

Humoral Response to Hepatitis B and COVID-19 Vaccine among Maintenance Hemodialysis Patients.

Maintenance hemodialysis (MHD) patients have impaired immunological responses to pathogens and vaccines. In this study, we compared the humoral response to HBV and COVID-19 vaccines in a cohort of MHD patients. Demographic and clinical characteristics of vaccine responders and non-responders were also compared, and the association between the humoral responses to both vaccines was evaluated. The cohort included 94 MHD patients who were vaccinated at least once for HBV and twice for COVID-19. Among the 94 patients, 28 (29.8%) did not develop protective titers to HBV. Hypertension, coronary heart disease, and heart failure were more common in non-responders. Among MHD patients, 85% had positive IgG anti-spike SARS-CoV-2 levels 6 months after two doses of BNT162b2 (Pfizer/Biotech) vaccine. Age and immunosuppressive therapy were the main predictors of humoral response to COVID-19 vaccine. We did not find any association between non-responders to HBV and non-responders to COVID-19 vaccine. There was no difference in IgG anti-spike titers between HBV responders and non-responders (505 ± 644 vs. 504 ± 781, p = 0.9) Our results suggest that reduced humoral response to hepatitis B is not associated with reduced response to COVID-19 vaccine. Different risk-factors were associated with poor immune response to HBV and to COVID-19 vaccines.

Humoral Response and Breakthrough Infections With SARS-COV-2 B.1.617.2 Variant in Vaccinated Maintenance Hemodialysis Patients

BACKGROUND AND AIMS Breakthrough COVID-19 may occur in vaccinated people and may result from declining vaccine effectiveness or highly transmittable SARS-CoV-2 variants, such as the B.167.2 (delta) variant. The recent emergence of the Omicron (B.1.1.529) variant has heightened this issue. We investigated risk factors and outcomes for infection with the delta variant among vaccinated hemodialysis patients. METHOD Patients on maintenance hemodialysis who received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine were categorized into the study group who developed COVID-19 and controls who did not in retrospective, observational and comparative study. We compared risk factors for developing COVID-19 between two study groups and assessed clinical outcomes, including 30-day mortality rates. RESULTS A total of 25 cases of breakthrough SARS-CoV-2 infection were compared with 91 controls without. Breakthrough infection was associated with chronic immunosuppressive treatment, hematological malignancies and low antibody levels against SARS-CoV-2 spike protein (P = 0.001, 0.006 and 0.4, respectively). All COVID-19 cases occurred at least 5-months after vaccination and were caused by the B.1.617.2 variant in at least 23/25 cases. COVID-19 was categorized as severe or critical disease in 11/25 patients (44%) and 52% required hospitalization and COVID-19-directed treatment. The source of infection was nosocomial in 6/25 cases (24%), and healthcare-related in additional 3/25 (12%). Mortality rate was 20%, and overall mortality was significantly higher in subjects who developed COVID-19 than in controls (odds ratio for all-cause mortality 7.3, 95% confidence interval 1.6–33.2;P = 0.004). CONCLUSION Breakthrough COVID-19 with the B.1.617.2 variant can occur in vaccinated hemodialysis patients and is associated with immunosuppression and a weaker vaccine immune response. Infections may be nosocomial and result in significant morbidity and mortality.FIGURE 1: Box plot of baseline IgG anti-S titer in study groups: Mean IgG anti-spike levels in the study group were 89.1 ± 114.5 AU/mL versus 533.7 ± 726.8 AU/mL in the control group, P = 0.1.

Humoral Response and SARS-CoV-2 Infection Risk following the Third and Fourth Doses of the BNT162b2 Vaccine in Dialysis Patients.

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses.

Humoral response and breakthrough infections with SARS-CoV-2 B.1.617.2 variant in vaccinated maintenance hemodialysis patients.

INTRODUCTION: Breakthrough COVID-19 may occur in vaccinated people, and may result from declining vaccine effectiveness or highly transmittable SARS-CoV-2 variants, such as the B.167.2 (delta) variant. We investigated risk factors and outcomes for infection with the delta variant among vaccinated hemodialysis patients. METHODS: Patients on maintenance hemodialysis who received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine were analysed according to having developed COVID-19 (study group) or not (control group), in a retrospective, observational, comparative study. We compared risk-factors for developing breakthrough COVID-19 and assessed clinical outcomes, including 30-day mortality rates. RESULTS: Twenty-four cases of breakthrough SARS-CoV-2 infection were compared to 91 controls without infection. Breakthrough infection was associated with chronic immunosuppressive treatment, hematological malignancies, and low antibody levels against SARS-CoV-2 spike protein. All COVID-19 cases occurred at least 5 months after vaccination, and most were caused by the B.1.617.2 variant (at least 23/24 cases). COVID-19 was categorized as severe or critical disease in 11/24 patients (46%), and 54% required hospitalization and COVID-19-directed treatment. The source of infection was nosocomial in 6/24 cases (25%), and healthcare-related in 3/24 (12.5%). Mortality rate was 21%. Overall mortality was significantly higher in patients who developed COVID-19 than in controls (odds ratio for all-cause mortality 7.6, 95% CI 1.4-41, p = 0.002). CONCLUSIONS: Breakthrough COVID-19 with the B.1.617.2 variant can occur in vaccinated hemodialysis patients and is associated with immunosuppression and weaker humoral response to vaccination. Infections may be nosocomial and result in significant morbidity and mortality.

Humoral Response to the Third Dose of Sars-Cov-2 Vaccine in Kidney Transplant Recipients.

BACKGROUND: Most solid organ transplant recipients did not develop an appreciable serologic response after 2 doses of the mRNA SARS-CoV-2 vaccine. METHODS: We analyzed the humoral response after a third dose of the BNT162b2 vaccine in 130 kidney transplant recipients, compared to 48 health care workers, and associated factors, including prevaccine cellular immune response, by evaluating intracellular cytokine production after stimulation of donor's peripheral blood mononuclear cells. RESULTS: After 2 doses, most of the controls (47 out of 48, 98%) and only 40% of kidney recipients (52 of 130) kidney recipients were seropositive (P < .001). Most seronegative recipients developed a serologic response after the booster (47 out 78, 60%), thus bringing the total number of seropositive recipients to 99 out of 130 (76%). After the third dose, there was a significant increase in antibodies titers in both groups. Decreased humoral response was significantly associated with an older age, lower lymphocyte count, and a lower level of antibodies before booster administration. CD4+TNFα+ and CD4+INFγ+ were correlated with mean increase in antibody titers. CONCLUSIONS: A third dose of the BNT162b2 mRNA vaccine in kidney recipients is safe and effectively results in increased IgG anti-S levels, including in individuals who were seronegative after 2 doses. Long-term studies of the length of the immune response and protection are required.

Humoral Response to Pfizer BNT162b2 Vaccine Booster in Maintenance Hemodialysis Patients.

INTRODUCTION: Coronavirus disease is associated with increased morbidity and mortality in maintenance hemodialysis (MHD) patients. Recent breakthrough infection in vaccinated people has led some authorities to recommend a booster dose for patients fully vaccinated 5-8 months ago. We aimed to assess the humoral response of MHD patients following a booster dose with the BNT162b2 vaccine. METHODS: The study included 102 MHD patients vaccinated with 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine. A third dose (booster) was recommended to all MHD patients in our center and was given to those who opted to receive it, resulting in a booster group and a control group that did not receive the booster. Previous exposure was excluded by testing for the presence of the anti-nucleocapsid antibody (SARS-CoV-2) or positive PCR. We assessed the humoral response before and after the booster dose. RESULTS: Of 66 patients in the booster group, 65 patients (98.5%) developed a positive antibody response, from 472.7 ± 749.5 to 16,336.8 ± 15,397.3, as compared to a sustained decrease in the control group (695.7 ± 642.7 to 383.6 ± 298.6), p < 0.0001. No significant adverse effects were reported. Prior antibody titers were positively correlated to IgG levels following the booster dose. There was a significant association between malnutrition-inflammation markers and the humoral response. CONCLUSIONS: Almost all MHD patients developed a substantial humoral response following the booster dose, which was significantly higher than levels reported for MHD patients following administration of 2 doses alone. Further studies and observations are needed to determine the exact timing and dosing schedule.

Kidney transplant recipients vaccinated before transplantation maintain superior humoral response to SARS-CoV-2 vaccine.

Majority of transplant recipients did not develop an appreciable humoral response following SARS-CoV-2 vaccine, in contrast to dialysis patients and healthy individuals. We analyzed the serologic response to BNT162b2 (Pfizer-BioNTech) vaccine in a cohort of 19 kidney transplant recipients, vaccinated prior to transplantation, compare to 109 recipients vaccinated after transplantation, and to 39 healthcare workers, by determining the level of anti-spike antibodies after transplantation. All controls and 17 of 19 (90%) of recipients vaccinated before transplant were seropositive, while only 49 of 109 (45%) recipients vaccinated post-transplant had positive serology (P < .001). Median anti-spike IgG in the group of kidney transplant recipients vaccinated after transplantation (10.7 AU/ml, [IQR 0-62.5]) was lower than the patients vaccinated before transplantation (66.2 AU/ml [21.6-138]), which was significantly lower than in the controls (156 AU/ml [99.7-215.5]). Negative humoral response was associated with vaccination post transplantation (odds ratio 22.4), older age (OR = 1.04), and longer time on dialysis (OR = 1.02), while higher lymphocyte count at time of vaccination was protective (OR = .52). Our findings of sustained superior humoral response to SARS-CoV-2 vaccine in kidney transplant recipients vaccinated prior to transplantation strongly support the recommendations of SARS-CoV-2 vaccination of transplant candidates, especially those younger than 60 years.

Occurrence of BNT162b2 Vaccine Adverse Reactions Is Associated with Enhanced SARS-CoV-2 IgG Antibody Response.

Promoting SARS-CoV-2 vaccination has been a global mission since the first vaccines were approved for emergency use. Alongside the excitement following the possibility of eradicating SARS-CoV-2 and ending the COVID-19 pandemic, there has been ample vaccine hesitancy, some due to the abundant reporting of adverse reactions. We report here that the occurrence of BNT162b2 vaccine adverse reactions is associated with enhanced antibody response. We found a statistically significant correlation between having an adverse reaction, whether local or systemic, and higher antibody levels. No sex difference was observed in antibody levels. However, as was recently reported, the antibody response was found to be lower among older vaccinees. The demonstration of a clear correlation between adverse reactions and antibody levels may help reduce vaccination hesitancy by reassuring that the presence of such reactions is an indication of a well-functioning immune system.

Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus.

COVID-19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS-CoV-2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer-BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS-CoV-2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti-spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17-2.69]), high-dose corticosteroids in the last 12 months (1.3 [1.09-1.86]), maintenance with triple immunosuppression (1.43 [1.06-2.15]), and regimen that includes mycophenolate (1.47 [1.26-2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID-19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.

Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with higher morbidity and mortality in patients on maintenance hemodialysis. Patients on dialysis tend to have a reduced immune response to infection or vaccination. We aimed to assess, for the first time to the best of our knowledge, the humoral response following vaccination with the BNT162b2 vaccine in patients on maintenance hemodialysis and the factors associated with it. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study included 56 patients on maintenance hemodialysis (dialysis group) and a control group composed of 95 health care workers. All participants had received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine. The serology testing was done using Quant II IgG anti-Spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay by Abbott a median of 30 days after receipt of the second dose of the vaccine. RESULTS: All subjects in the control group developed an antibody response compared with 96% (54 of 56) positive responders in the dialysis group. The IgG levels in the dialysis group (median, 2900; interquartile range, 1128-5651) were significantly lower than in the control group (median, 7401; interquartile range, 3687-15,471). A Mann-Whitney U test indicated that this difference was statistically significant (U=1238; P<0.001). There was a significant inverse correlation of age and IgG levels in both groups. The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; 95% confidence interval, 1.08 to 1.20; P=0.004) and for the dialysis group compared with the control group (odds ratio, 2.7; 95% confidence interval, 1.13 to 7.51; P=0.05). Within the dialysis group, older age and lower lymphocyte count were associated with antibody response in the lower quartile (odds ratio, 1.22 per 1-year older; 95% confidence interval, 1.13 to 1.68; P=0.03 and odds ratio, 0.83 per 10-e3/µl-higher lymphocyte count; 95% confidence interval, 0.58 to 0.97; P=0.05). CONCLUSIONS: Although most patients on maintenance hemodialysis developed a substantial humoral response following the BNT162b2 vaccine, it was significantly lower than controls. Age was an important factor in the humoral response, regardless of chronic medical conditions.