Deficient SARS-CoV-2 hybrid immunity during inflammatory bowel disease

Clin Immunol. 2025 Feb:271:110404. doi: 10.1016/j.clim.2024.110404. Epub 2024 Dec 5.

Abstract

Patients with Inflammatory Bowel Disease (IBD) undergoing immunosuppressive therapies face heightened susceptibility to severe COVID-19. An in-depth understanding of systemic inflammation and cellular immune responses after SARS-CoV-2 vaccination and breakthrough infections (BTI) is required for optimizing vaccine strategies in this population. While the prevalence of high serological responders post- third COVID-19 vaccine dose was lower, and the antibody waning was higher in IBD patients than in healthy donors (HD), IBD patients showed an increase in anti-RBD Wild Type IgG levels and cross-reactive Spike -specific memory B cells following BTI. However, there was no significant enhancement in cellular immune responses against anti-SARS-CoV-2 post-BTI, with responses instead characterized by activation of SARS-CoV-2 specific and also bystander CD8 T cells. These results suggest a complex interaction between chronic inflammation in IBD and the generation of new immune responses, highlighting the need for tailored vaccine regimens and anti-inflammatory therapies to boost cellular immunity against SARS-CoV-2.

Keywords: Activation; Antibody waning; Hybrid immunity; IBD; Inflammation; TNF inhibitors.

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunity, Cellular
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Inflammatory Bowel Diseases* / drug therapy
  • Inflammatory Bowel Diseases* / immunology
  • Male
  • Memory B Cells / immunology
  • Middle Aged
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology

Substances

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