Catch-up antibody responses and hybrid immunity in mRNA vaccinated patients at risk of severe COVID-19

Infect Dis (Lond). 2023 Oct;55(10):744-750. doi: 10.1080/23744235.2023.2230289. Epub 2023 Jul 3.


Background: The immunogenicity of repeated vaccination and hybrid immunity in vulnerable patients remains unclear.

Methods: We studied the impact of iterative Covid-19 mRNA vaccination and hybrid immunity on antibody levels in immunosuppressed subjects. Patients with liver cirrhosis (n = 38), survivors of allogeneic haematopoietic stem cell transplantation (allo-HSCT) (n = 36) and patients with autoimmune liver disease (n = 14) along with healthy controls (n = 20) were monitored for SARS-CoV-2-S1 IgG after their 1st-3rd vaccine doses, 31 of whom became infected with the Omicron variant after the 2nd dose. Ten uninfected allo-HSCT recipients received an additional 4th vaccine dose.

Results: Unexpectedly, immunosuppressed patients achieved antibody levels in parity with controls after the 3rd vaccine dose. In all study cohorts, hybrid immunity (effect of vaccination and natural infection) resulted in approximately 10-fold higher antibody levels than vaccine-induced immunity alone.

Conclusions: Three doses of the Covid-19 mRNA vaccine entailed high antibody concentrations even in immunocompromised individuals, and hybrid-immunity resulted further augmented levels than vaccination alone. Clinical trial registration: EudraCT 2021-000349-42.

Keywords: SARS-CoV-2; allogeneic haematopoietic stem cell transplantation; autoimmune hepatitis; cirrhosis; hybrid immunity; mRNA vaccination.

MeSH terms

  • Antibodies, Viral
  • Antibody Formation
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunoglobulin G
  • Pregnancy
  • Pregnancy Complications, Infectious*
  • RNA, Messenger
  • SARS-CoV-2
  • Vaccination


  • COVID-19 Vaccines
  • Antibodies, Viral
  • Immunoglobulin G
  • RNA, Messenger

Supplementary concepts

  • SARS-CoV-2 variants