Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and in liver transplant recipients.
Murray SM., Pose E., Wittner M., Londoño M-C., Schaub G., Cook J., Dimitriadis S., Meacham G., Irwin S., Lim Z., Duengelhoef P., Sterneck M., Lohse AW., Perez V., Trivedi P., Bhandal K., Mullish B., Manousou P., Provine NM., Avitabile E., Carroll M., Tipton T., Healy S., Burra P., Klenerman P., Dunachie S., Kronsteiner B., Maciola AK., Pasqual G., Hernandez-Gea V., Garcia-Pagan JC., Lampertico P., Iavarone M., Gines P., Lütgehetmann M., Schulze Zur Wiesch J., Russo FP., Barnes E., Marjot T., OCTAVE Collaborative Group, PITCH study, and the EASL supported COVID-Hep vaccine network None., OCTAVE Collaborative Group None., PITCH Consortium None., EASL supported COVID-Hep vaccine network None.
BACKGROUND AND 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 vaccines alongside COVID-19 clinical outcomes. METHODS: 849 participants with cirrhosis, autoimmune hepatitis (AIH), vascular liver disease (VLD), liver transplant recipients (LTR) and healthy controls (HC) were recruited from 4 countries. Standardised immune assays were performed pre and post three vaccines (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 HC post-V3. LTR 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 LTR. 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 LTR 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, LTR 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 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 liver patients.