Accelerated waning of immune responses to a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases

J Autoimmun. 2023 Feb:135:102981. doi: 10.1016/j.jaut.2022.102981. Epub 2022 Dec 22.

Abstract

Background: A 3rd COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed. Currently it remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses.

Methods: 50 patients under immunosuppression and 42 healthy controls (HCs) received a 3rd dose of an mRNA-based vaccine and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 Spike immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period.

Results: At week 12, reduced anti-RBD antibody levels were observed in IMID patients as compared to HCs (median antibody level 5345 BAU/ml [1781-10,208] versus 9650 BAU/ml [6633-16,050], p < 0.001). Reduction in relative antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p < 0.001). Lowest anti-RBD antibody levels were detected in IMID patients who received biological disease-modifying anti-rheumatic drugs (DMARDs) or a combination therapy with conventional synthetic and biological DMARDs. Number of SARS-CoV-2-specific T cells against wildtype and Omicron variants remained stable over 12 weeks in IMID patients. No serious adverse events were reported.

Conclusion: Due to a fast decline in anti-RBD antibodies in IMID patients an early 4th vaccination should be considered in this vulnerable group of patients.

Keywords: COVID-19; Immunosuppression; SARS-CoV-2; Vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • Antibodies, Viral
  • Antirheumatic Agents*
  • COVID-19 Vaccines
  • COVID-19*
  • Humans
  • Immunity, Humoral
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Vaccination

Substances

  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Antibodies
  • Antirheumatic Agents
  • Antibodies, Viral
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants