Abstract
Background & Aims: Comparative assessments of immunogenicity following different COVID-19 vaccines in patients with distinct liver diseases are lacking. SARS-CoV-2-specific T-cell and antibody responses were evaluated longitudinally after one to three vaccine doses, with long-term follow-up for COVID-19-related clinical outcomes.
Methods: A total of 849 participants (355 with cirrhosis, 74 with autoimmune hepatitis [AIH], 36 with vascular liver disease [VLD], 257 liver transplant recipients [LTRs] and 127 healthy controls [HCs]) were recruited from four countries. Standardised immune assays were performed pre and post three vaccine doses (V1-3).
Results: In the total cohort, there were incremental increases in antibody titres after each vaccine dose (p <0.0001). Factors associated with reduced antibody responses were age and LT, whereas heterologous vaccination, prior COVID-19 and mRNA platforms were associated with greater responses. Although antibody titres decreased between post-V2 and pre-V3 (p = 0.012), patients with AIH, VLD, and cirrhosis had equivalent antibody responses to HCs post-V3. LTRs had lower and more heterogenous antibody titres than other groups, including post-V3 where 9% had no detectable antibodies; this was heavily influenced by intensity of immunosuppression. Vaccination increased T-cell IFNγ responses in all groups except LTRs. Patients with liver disease had lower functional antibody responses against nine Omicron subvariants and reduced T-cell responses to Omicron BA.1-specific peptides compared to wild-type. 122 cases of breakthrough COVID-19 were reported of which 5/122 (4%) were severe. Of the severe cases, 4/5 (80%) occurred in LTRs and 2/5 (40%) had no serological response post-V2.
Conclusion: After three COVID-19 vaccines, patients with liver disease generally develop robust antibody and T-cell responses to vaccination and have mild COVID-19. However, LTRs have sustained no/low antibody titres and appear most vulnerable to severe disease.
Impact and implications: Standardised assessments of the immune response to different COVID-19 vaccines in patients with liver disease are lacking. We performed antibody and T-cell assays at multiple timepoints following up to three vaccine doses in a large cohort of patients with a range of liver conditions. Overall, the three most widely available vaccine platforms were immunogenic and appeared to protect against severe breakthrough COVID-19. This will provide reassurance to patients with chronic liver disease who were deemed at high risk of severe COVID-19 during the pre-vaccination era, however, liver transplant recipients had the lowest antibody titres and remained vulnerable to severe breakthrough infection. We also characterise the immune response to multiple SARS-CoV-2 variants and describe the interaction between disease type, severity, and vaccine platform. These insights may prove useful in the event of future viral infections which also require rapid vaccine development and delivery to patients with liver disease.
| Original language | English |
|---|---|
| Pages (from-to) | 109-123 |
| Number of pages | 15 |
| Journal | Journal of Hepatology |
| Volume | 80 |
| Issue number | 1 |
| Early online date | 19 Oct 2023 |
| DOIs | |
| Publication status | Published - Jan 2024 |
Bibliographical note
Funding Information:The COVID-Hep vaccine network is supported by a registry grant from the European Association for the Study of the Liver (EASL). The UK OCTAVE study is funded by a grant from UK Research and Innovation (UKRI) administered by the Medical Research Council (reference: MC_PC_20031). PITCH is funded by the UK Department of Health and Social Care by UKRI as part of “Investigation of proven vaccine breakthrough by SARS-CoV-2 variants in established UK healthcare worker cohorts: SIREN consortium & PITCH Plus Pathway (reference: MR/W02067X/1), with contributions from UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK–CIC), the Huo Family Foundation and the NIHR UKRIDHSC COVID-19 Rapid Response Rolling Call (reference: COV19-RECPLAS). SMM is supported by the Medical Research Council. T.M. is supported via a Wellcome Trust Clinical Research Training Fellowship (reference: 102176/B/13/Z). E.B. is supported by the Oxford NIHR Biomedical Research Centre and is an NIHR Senior Investigator. P.J.T receives institutional salary support from the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC). BHM is the recipient of an NIHR Academic Clinical Lectureship (CL-2019-21-002). A.W.L, J.S.z.W., M.L, receive financial support from the German Center for Infection Research (DZIF). Part of the work of this study (P.G.) has been funded by a grant of the Instituto de Salud Carlos III-ISCIII, grant number: PI020/00579. The Division of Digestive Diseases at Imperial College London receives financial and infrastructure support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.
Publisher Copyright:
© 2023 The Author(s)
Keywords
- Antibodies
- Autoimmune hepatitis
- Cirrhosis
- COVID-19
- Liver transplantation
- SARS-CoV-2
- T cells
- Vaccination
- Variants of Concern
- Vascular liver disease
ASJC Scopus subject areas
- Hepatology
