Abstract
BACKGROUND: The clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established. PATIENTS AND METHODS: A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3-6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders. RESULTS: At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 days (range 7-195) after full vaccination. The incidence rate was 6.39 per 100 persons-year. Most patients were asymptomatic (19/37, 51.4%), whereas only 19% developed pneumonia. The mortality rate was 8%. Lack of detectable antibodies at 3-6 weeks after full vaccination was the only variable associated with breakthrough infection in multivariate logistic regression analysis (Odds Ratio 2.35, 95% confidence interval 1.2-4.6, p = 0.012). Median antibody titers were lower in cases than in non-cases [1.83 binding antibody units (BAU)/mL (range 0-4854.93) vs 730.81 BAU/mL (range 0-56,800), respectively (p = 0.007)]. We identified 250 BAU/mL as a cutoff above which incidence and severity of the infection were significantly lower. CONCLUSIONS: Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants.