Risk Factors for Low Humoral Response to BNT-162b2 In Hemodialysis Patients

Introduction

Maintenance Hemodialysis (HD) patients are at higher risk of both infection and mortality associated with the new coronavirus 2. Immunization through large-scale vaccination is the cornerstone of infection prevention in this population. This study aims to identify risk factors for low response to the BNT-162b2 (Pfizer BioNTech) vaccine in a HD cohort.

Materials and Methods

Observational prospective study of a HD group followed in a Portuguese Public Founded Hemodialysis Center who received BNT-162b2 vaccination. Specific anti-Spike IgG was evaluated as arbitrary units per milliliter (AU/mL) on two separate occasions: 3 weeks after the first dose and 3 weeks after the second. IgG titers, Non-Responders (NR), and Weak-Responders (WR) after each dose were evaluated against risk factors that included demographic, clinical and analytical variables.

Results

Humoral response evaluated by IgG anti-Spike levels showed a strong correlation with Charlson comorbidity index (CCI) and intact parathormone (iPTH) after each inoculation (1 ^st dose: ρ=−0.64/0.54; 2 ^nd dose: ρ=−0.66/0.63, respectively; p<0.01 throughout). After completing both doses: 1) NR were associated with female sex (p<0.01), lower albumin and iPTH (p=0.01); 2) WR showed higher CCI, older age, lower iPTH and lower albumin (p=<0.01, p=0.03, p<0.01, p=0.05, respectively) and, consistently, associated with CCI over 8, age over 75, iPTH under 150 ng/L, female sex, dialysis vintage under 24 months and central venous catheter (CVC) over arteriovenous fistula (p=0.01, p=0.03, p<0.01, p=0.01, p=0.01, p<0.01, respectively). A binary regression model using CCI, sex (male) and CVC was statistically significant in prediction of WR after the 2 ^nd dose with OR (95% CI): 1.81 (1.06-3.08); 0.05 (0.01-0.65); 13.55 (1.06-174.18), respectively (p=0.01).

Conclusion

Older age, higher CCI, lower iPTH and albumin, CVC as vascular access and recent hemodialysis initiation (less than 2 years) associate with lower response to vaccination in our study. A higher comorbidity burden is suggested as a more significant surrogate marker for low immunogenicity rather than age alone. Identifying HD patients as a population at high-risk for low response to vaccination is essential for proper policy-making, facilitating the implementation of adequate and individualized contingency protocols.

What is already known about this subject

• Maintenance hemodialysis patients have lower humoral response to BNT-162b2 COVID-19 vaccine when compared to the general population.

• Maintenance dialysis patients are at high risk of exposure to coronavirus 2 in addition to a more severe disease course.

What this study adds

• We suggest Charlson commorbidity index, older age, intact parathormone, central venous catheter as vascular access and lower dialysis vintage as possible surrogate markers of immunogenicity in HD patients.

• There is a low humoral response after a single dose of the vaccine (50%) that can be increased after the second (86%).

What impact this may have on practice or policy

• Strict Protocols for follow-up measures in HD patients, including closer humoral titers assessment, risk stratification, adequate isolation, and surveillance of symptoms might be necessary in order to improve this population survival/life expectancy.

• Screening HD patients, seroconversion rates may be improved by giving extra inoculations for patients at risk for low response.