Improved Immunologic Response to COVID-19 Vaccine with Prolonged Dosing Interval in Hemodialysis Patients

BACKGROUND AND AIMS Vaccination against coronavirus disease 2019 (COVID-19) can reduce disease incidence and severity. Dialysis patients demonstrate a delayed immunologic response to vaccines. We determined factors affecting the immunologic response to COVID-19 vaccines in hemodialysis patients. METHOD All patients within a Swedish hemodialysis network, vaccinated with two doses of COVID-19 vaccine 2–8 weeks before inclusion, were eligible for this cross-sectional study. Severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody levels were determined by the EliA SARS-CoV-2-Sp1 IgG test (Thermo Fisher Scientific, Phadia AB) and related to clinical and demographic parameters. Eighty-nine patients were included. RESULTS Patients were vaccinated with two doses of Comirnaty (BNT162b2, 73%) or Spikevax (mRNA-1273, 23.6%). Three patients received combinations of different vaccines. Response rate (antibody titres >7 U/mL) was 89.9%, while 39.3% developed high antibody titres (>204 U/mL), 47 (43–50) days after the second dose. A previous COVID-19 infection associated with higher antibody titres [median (25th–75th percentile) 1558.5 (814.5–3763.8) U/mL versus 87 (26–268) U/mL;P = 0.002], while the time between vaccine doses did not differ between groups (P = 0.7). Increasing SARS-CoV-2 antibody titres were independently associated with increasing time between vaccine doses, decreasing serum calcium levels and previous COVID-19 (Table 1). CONCLUSION In conclusion, a longer interval between COVID-19 mRNA vaccine doses, lower calcium and a previous COVID-19 infection were independently associated with a stronger immunologic vaccination response in hemodialysis patients. While the response rate was good, only a minority developed high antibody titres 47 (43–50) days after the second vaccine dose.Table 1. Multiple regression of predictors of SARS-CoV-2 spike IgG response to COVID-19 vaccinesRegression coefficient(95% CI)P(Constant)0.015 (–0.507 to 0.537)0.95Type of vaccine–0.194 (–0.566 to 0.179)0.30Sodium (1 SD)–0.154 (–0.309 to 0.001)0.051Calcium (1 SD)–0.233 (–0.4 to –0.067)0.007Treatment time (1 SD)–0.05 (–0.234 to 0.133)0.586Bodymass index (1 SD)0.104 (–0.086 to 0.294)0.279IDBWG (1 SD)0.118 (–0.042 to 0.278)0.145Kt/V (1 SD)0.009 (–0.159 to 0.177)0.915Vaccine interval (1 SD)0.241 (0.039 to 0.443)0.02Interval first dose to sample (1 SD)0.027 (–0.142 to 0.197)0.750Previous COVID-191.078 (0.56 to 1.596)<0.001

Improved immunologic response to COVID-19 vaccine with prolonged dosing interval in haemodialysis patients.

Vaccination against 2019 coronavirus disease (COVID-19) can reduce disease incidence and severity. Dialysis patients demonstrate a delayed immunologic response to vaccines. We determined factors affecting the immunologic response to COVID-19 vaccines in haemodialysis patients. All patients within a Swedish haemodialysis network, vaccinated with two doses of COVID-19 vaccine 2-8 weeks before inclusion, were eligible for this cross-sectional study. Severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody levels were determined by EliA SARS-CoV-2-Sp1 IgG test (Thermo Fisher Scientific, Phadia AB) and related to clinical and demographic parameters. Eighty-nine patients were included. Patients were vaccinated with two doses of Comirnaty (BNT162b2, 73%) or Spikevax (mRNA-1273, 23,6%). Three patients received combinations of different vaccines. Response rate (antibody titres >7 U/mL) was 89.9%, while 39.3% developed high antibody titres (>204 U/mL), 47 (43-50) days after the second dose. A previous COVID-19 infection associated with higher antibody titres (median (25th-75th percentile) 1558.5 (814.5-3,763.8) U/mL vs 87 (26-268) U/mL, P = .002), while time between vaccine doses did not differ between groups (P = .7). Increasing SARS-CoV-2 antibody titres were independently associated with increasing time between vaccine doses (B 0.241, P = .02), decreasing serum calcium levels (B -0.233, P = .007) and previous COVID-19 (B 1.078, P < .001). In conclusion, a longer interval between COVID-19 mRNA vaccine doses, lower calcium and a previous COVID-19 infection were independently associated with a stronger immunologic vaccination response in haemodialysis patients. While the response rate was good, only a minority developed high antibody titres, 47 (43-50) days after the second vaccine dose.

Time-dependent evolution of IgG antibody levels after first and second dose of mRNA-based SARS-CoV-2 vaccination in haemodialysis patients: a multicentre study.

BACKGROUND: Vaccination programs are essential for the containment of the coronavirus disease 2019 pandemic, which has hit haemodialysis populations especially hard. Early reports suggest a reduced immunologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in dialysis patients, in spite of a high degree of seroconversion. We aimed to identify risk factors for a reduced efficacy of an mRNA vaccine in a cohort of haemodialysis patients. METHOD: In a multicentre study, including 294 Portuguese haemodialysis patients who had received two doses of BNT162b2 with a 3-week interval, immunoglobulin G-class antibodies against the SARS-CoV-2 spike protein were determined 3 weeks after the first dose (M1) and 6 weeks after the second dose (M2). The threshold for seroconversion was 10 UR/mL. Demographic and clinical data were retrieved from a quality registry. Adverse events were registered using a questionnaire. RESULTS: At M2, seroconversion was 93.1% with a median antibody level of 197.5 U/mL (1.2-3237.0) and a median increase of 180.0 U/mL (-82.9 to 2244.6) from M1. Age [beta -8.9; 95% confidence interval (95% CI) -12.88 to -4.91; P < 0.0001], ferritin >600 ng/mL (beta 183.93; 95% CI 74.75-293.10; P = 0.001) and physical activity (beta 265.79; 95% CI 30.7-500.88; P = 0.03) were independent predictors of SARS-CoV-2 antibody levels after two vaccine doses. Plasma albumin >3.5 g/dL independently predicted the increase of antibody levels between both doses (odds ratio 14.72; 95% CI 1.38 to 157.45; P = 0.03). Only mild adverse reactions were observed in 10.9% of patients. CONCLUSIONS: The SARS-CoV-2 vaccine BNT162b2 is safe and effective in haemodialysis patients. Besides age, iron status and nutrition are possible modifiable modulators of the immunologic response to SARS-CoV-2 mRNA vaccines. These data suggest the need for an early identification of populations at higher risk for diminished antibody production and the potential advantage of the implementation of oriented strategies to maximize the immune response to vaccination in these patients.

Immunogenicity and tolerability of COVID-19 vaccination in peritoneal dialysis patients-A prospective observational cohort study.

BACKGROUND: In peritoneal dialysis (PD) patients, information on the immunogenicity and tolerability of SARS-CoV-2 vaccination is still scarce. We compared the immunogenicity and tolerability of SARS-CoV-2 vaccination of PD patients with that of medical personnel. METHODS: In a prospective observational cohort study, PD patients and immunocompetent medical personnel were evaluated for SARS-CoV-2 spike-IgG- and Nucleocapsid-IgG-antibody-levels before, 2 weeks after the first, and 6 weeks after the second SARS-CoV-2 vaccination and vaccine tolerability after the first and second vaccination. RESULTS: In COVID-19-naïve PD patients (N = 19), lower SARS-CoV-2-spike-IgG-levels were found compared with COVID-19-naïve medical personnel (N = 24) 6 weeks after second vaccination (median 1438 AU/ml [25th-75th percentile 775-5261] versus 4577 [1529-9871]; p = 0.045). This finding resulted in a lower rate of strong vaccine response (spike-IgG ≥ 1000 AU/ml) of COVID-19-naïve PD patients compared with medical personnel (58% versus 92%; p = 0.013), but not for seroconversion rate (spike-IgG ≥ 50 AU/ml: 100% vs. 100%; p > 0.99). After first vaccination, COVID-naïve PD patients presented with significantly fewer side effects than medical personnel (number of any side effect: 1 [1-2] vs. 4 [1-7]; p = 0.015). A similar pattern with slightly decreased frequencies of side effects was observed for tolerability of second SARS-CoV-2 vaccination in PD patients and medical personnel (number of any side effects: 1 [1-1] vs. 2 [1-5]; p = 0.006). CONCLUSIONS: SARS-CoV-2 vaccination in COVID-19-naïve PD patients appeared to induce a very high rate of seroconversion but a substantially lower rate of patients with a strong response compared with medical personnel. Vaccination appeared to be safe in the PD patients studied.

Immunogenicity of a first dose of mRNA- or vector-based SARS-CoV-2 vaccination in dialysis patients: a multicenter prospective observational pilot study.

BACKGROUND: Dialysis patients are at risk for lower SARS-CoV-2-vaccine immunogenicity than the normal population. We assessed immunogenicity to a first mRNA- or vector-based SARS-CoV-2-vaccination dose in dialysis patients. METHODS: In a multicenter observational pilot study, 2 weeks after a first vaccination (BNT162b2/Pfizer-BioNTech [Comirnaty] or ChAdOx1 nCoV-19/Oxford-Astra-Zeneca [Vaxzevria]), hemodialysis patients (N = 23), peritoneal dialysis patients (N = 4) and healthy staff (N = 14) were tested for SARS-CoV-2-spike IgG/IgM, Nucleocapsid-protein-IgG-antibodies and plasma ACE2-receptor-binding-inhibition capacity. Hemodialysis patients who had had prior COVID-19 infection (N = 18) served as controls. Both response to first SARS-CoV-2 vaccination and IgG spike-positivity following prior COVID-19 infection were defined as SARS-CoV-2 spike IgG levels ≥ 50 AU/mL. RESULTS: Vaccination responder rates were 17.4% (4/23) in hemodialysis patients, 100% (4/4) in peritoneal dialysis patients and 57.1% (8/14) in staff (HD vs. PD: p = 0.004, HD vs. staff: p = 0.027). Among hemodialysis patients, type of vaccine (Comirnaty N = 11, Vaxzevria N = 12, 2 responders each) did not appear to influence antibody levels (IgG spike: Comirnaty median 0.0 [1.-3. quartile 0.0-3.8] versus Vaxzevria 4.3 [1.6-20.1] AU/mL, p = 0.079). Of responders to the first dose of SARS-CoV-2 vaccination among hemodialysis patients (N = 4/23), median IgG spike levels and ACE2-receptor-binding-inhibition capacity were lower than that of IgG spike-positive hemodialysis patients with prior COVID-19 infection (13/18, 72.2%): IgG spike: median 222.0, 1.-3. quartile 104.1-721.9 versus median 3794.6, 1.-3. quartile 793.4-9357.9 AU/mL, p = 0.015; ACE2-receptor-binding-inhibition capacity: median 11.5%, 1.-3. quartile 5.0-27.3 versus median 74.8%, 1.-3. quartile 44.9-98.1, p = 0.002. CONCLUSIONS: Two weeks after their first mRNA- or vector-based SARS-CoV-2 vaccination, hemodialysis patients demonstrated lower antibody-related response than peritoneal dialysis patients and healthy staff or unvaccinated hemodialysis patients following prior COVID-19 infection.

Risk prediction of COVID-19 incidence and mortality in a large multi-national hemodialysis cohort: implications for management of the pandemic in outpatient hemodialysis settings.

BACKGROUND: Experiences from the first wave of the 2019 coronavirus disease (COVID-19) pandemic can aid in the development of future preventive strategies. To date, risk prediction models for COVID-19-related incidence and outcomes in hemodialysis (HD) patients are missing. METHODS: We developed risk prediction models for COVID-19 incidence and mortality among HD patients. We studied 38 256 HD patients from a multi-national dialysis cohort between 3 March and 3 July 2020. Risk prediction models were developed and validated, based on predictors readily available in outpatient HD units. We compared mortality among patients with and without COVID-19, matched for age, sex and diabetes. RESULTS: During the observational period, 1259 patients (3.3%) acquired COVID-19. Of these, 62% were hospitalized or died. Mortality was 22% among COVID-19 patients with odds ratios 219.8 [95% confidence interval (CI) 80.6-359] to 342.7 (95% CI 60.6-13 595.1), compared to matched patients without COVID-19. Since the first wave of the pandemic affected most European countries during the study, the risk prediction model for incidence of COVID-19 was developed and validated in European patients only [N = 22 826 area under the ROC curve(AUC)Dev 0.64, AUCVal 0.69]. The model for prediction of mortality was developed in all COVID-19 patients (AUCDev 0.71, AUCVal 0.78). Angiotensin receptor blockers were independently associated with a lower incidence of COVID-19 in European patients. CONCLUSIONS: We identified modifiable risk factors for COVID-19 incidence and outcome in HD patients. Our risk prediction tools can be readily applied in clinical practice. This can aid in the development of preventive strategies for future waves of COVID-19.