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

Abstract 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.