Longitudinal analysis of antibody responses to the Pfizer BNT162b2 vaccine in Patients Undergoing Maintenance Hemodialysis

Background and objectives: Patients undergoing hemodialysis are at higher risk of developing severe complications upon SARS-CoV-2 infection and were prioritized in the Portuguese vaccination campaign. Immunogenicity of COVID-19 vaccines in hemodialyzed patients was not addressed by the phase 3 clinical trials leading to their emergency approval. Design, setting, participants, and measurements: We performed a prospective, longitudinal, cohort analysis of 156 hemodialyzed patients and 143 age-matched controls scheduled for BTN162b2 vaccine. Excluded from analysis were five patients previously diagnosed with SARS-CoV-2, three sero-positive for anti-SARS-CoV-2 N, two dropouts and two deaths. ELISA was used to quantify anti-full-length Spike IgG, IgM and IgA levels in sera collected at day of the first vaccine dose (t0); 3 weeks later (day of the second dose, t1); and 3 weeks after the second inoculation (t2). Results: Seroconversion after the first vaccine dose (t1) was remarkably low in patients, with positivity for anti-spike IgG, IgM and IgA antibodies of 29.4%, 12% and 41%, respectively. The second vaccine dose raised seroconversion to 90.9% and 83.9% for IgG and IgA, respectively, while IgM positivity remained unchanged. At t1 the anti-Spike IgG level was significantly lower in patients with ages below 70 years when compared to age-matched controls, showing a profile similar to aged individuals (above 70 years). Immunosuppression was associated with lower antibody responses along the vaccine schedule (p=0.005 at t1; p=0.008 at t2). Noteworthy, previous unresponsiveness to hepatitis B vaccination (75/129, 58% of patients negative for anti-HBs antibodies) did not correlate with humoral unresponsiveness to BTN162b2. Other clinical and laboratory parameters had marginal correlations with response to vaccination. Conclusions: The large majority of hemodialyzed patients showed IgG seroconversion upon BNT162b2 mRNA vaccination but a sizable proportion of patients presented poor responses. These results support further investigation into the relationship between vaccination, serologic response and host protection.