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.

One-year dynamics of antibody titers after three doses of SARS-CoV-2 BNT162b2 vaccine.

BACKGROUND: A third dose of the BNT162b2 SARS-CoV-2 vaccine leads to a significant increase in antibody levels, however, concerns regarding the long-term persistence of this response exist. We assessed the humoral response for one year following vaccination. METHODS: A prospective study among immunocompetent healthcare workers (HCW) who received three doses of BNT162b2. anti-spike antibody titers were measured at six predefined timepoints, from before the second vaccine dose, and up to one year afterwards, which is 4-6 months after the third dose. HCW with a history of SARS-CoV-2 infection were excluded. RESULTS: Seventy-six HCW had all the six serological measurements. Antibody titers significantly increased shortly following the third vaccine dose, and while declining, remained higher from all previous measurements for up to six months. CONCLUSIONS: A third dose of BNT162b2 leads to a profound humoral response, which remains significantly higher than previous measurements, even after 6 months.

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.

Mortality prediction using a modified R2CHA2DS2-VASc score among hospitalized COVID-19 patients.

The CHA2DS2-VASc score incorporates several comorbidities which have prognostic implications in COVID-19. We assessed whether a modified score (M-R2CHA2DS2-VASc), which includes pre-admission kidney function and male sex, could be used to classify mortality risk among people hospitalized with COVID-19. This retrospective study included adults admitted for COVID-19 between March and December 2020. Pre-admission glomerular filtration rate (GFR) was calculated based on serum creatinine and used for scoring M-R2CHA2DS2-VASc. Participants were categorized according to the M-R2CHA2DS2-VASc categories as 0-1 (low), 2-3 (intermediate), or ≥ 4 (high), and according to initial COVID-19 severity score. The primary outcome was 30-day mortality rates. Secondary outcomes were mortality rates over time, and rates of mechanical ventilation, hemodynamic support, and renal replacement therapy. Eight hundred hospitalizations met the study criteria. Participants were 55% males, average age was 65.2 ± 17 years. There were similar proportions of subjects across the M-R2CHA2DS2-VASc categories. 30-day mortality was higher in those in higher M-R2CHA2DS2-VASc category and with severe or critical COVID-19 at admission. Subjects in the low, intermediate, and high M-R2CHA2DS2-VASc categories had 30-day mortality rates of 4.7%, 17% and 31%, respectively (p < 0.001). Higher category was also associated with increased need for mechanical ventilation and renal replacement therapy. All-cause 90-day mortality remained significantly associated with M-R2CHA2DS2-VASc. The M-R2CHA2DS2-VASc score is associated with 30-day mortality rates among patients hospitalized with COVID-19, and adds predictive value when combined with initial COVID-19 severity.

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.

Disease severity and renal outcomes of patients with chronic kidney disease infected with COVID-19.

INTRODUCTION: While there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney disease (CKD) on COVID-19 outcomes and its pathogenesis is currently lacking. METHODS: This retrospective, observational study evaluated the outcomes of all consecutive patients hospitalized during COVID-19 outbreaks in Meir Medical Center. Serum creatinine level was assessed before hospitalization ("baseline serum creatinine") and at admission, as well as minimum and maximum serum creatinine levels during hospitalization. RESULTS: Among 658 patients, 152 had eGFR < 60 ml/min (termed the CKD group), 506 patients served as controls. Patients in the CKD group were older, with higher prevalence of hypertension, diabetes mellitus and atherosclerosis. Disease severity and clinical presentation of CKD group were comparable to that of control group. Odds ratio for AKI was 5.8 (95%CI 3.8-8.7; p < 0.001) in CKD group vs. control group and 3.4 (95%CI 1.1-10.8) for renal replacement therapy (p < 0.026). Among the CKD group, 32.2% died after COVID-19 infection versus 14.8% of the controls (p < 0.001). Mortality increased as CKD stage increased (14.8% in controls, 29.6% in CKD stage 3, and 39.3% in CKD stages 4 and 5, p < 0.001). CONCLUSION: Despite comparable disease severity at presentation, patients with CKD had significantly more AKI events and required more renal replacement therapy during hospitalization than control patients did. Mortality increased as CKD stage increased.

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.