SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders

J Hematol Oncol. 2022 May 7;15(1):54. doi: 10.1186/s13045-022-01275-7.

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.

Keywords: Allogeneic stem cell transplantation; Autologous stem cell transplantation; Breakthrough SARS-CoV-2 infection; COVID-19; Correlates of protection; Hematological malignancies; Immunocompromised patients; Moderna mRNA-1273; Pfizer-BioNTech BNT162b2; SARS-CoV-2 vaccines; Vaccine.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • BNT162 Vaccine
  • COVID-19 Vaccines / therapeutic use
  • COVID-19* / epidemiology
  • COVID-19* / prevention & control
  • Cohort Studies
  • Hematologic Diseases* / complications
  • Hematologic Diseases* / therapy
  • Humans
  • Prospective Studies
  • SARS-CoV-2

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • BNT162 Vaccine

Supplementary concepts

  • SARS-CoV-2 variants