Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

Background &amp; 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 &lt;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.</p

Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

Background &amp; 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 &lt;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

Development of a sensitive Luminex xMAP-based microsphere immunoassay for specific detection of Iris yellow spot virus

Abstract Background Iris yellow spot virus (IYSV) is an Orthotospovirus that infects most Allium species. Very few approaches for specific detection of IYSV from infected plants are available to date. We report the development of a high-sensitive Luminex xMAP-based microsphere immunoassay (MIA) for specific detection of IYSV. Results The nucleocapsid (N) gene of IYSV was cloned and expressed in Escherichia coli to produce the His-tagged recombinant N protein. A panel of monoclonal antibodies (MAbs) against IYSV was generated by immunizing the mice with recombinant N protein. Five specific MAbs (16D9, 11C6, 7F4, 12C10, and 14H12) were identified and used for developing the Luminex xMAP-based MIA systems along with a polyclonal antibody against IYSV. Comparative analyses of their sensitivity and specificity in detecting IYSV from infected tobacco leaves identified 7F4 as the best-performed MAb in MIA. We then optimized the working conditions of Luminex xMAP-based MIA in specific detection of IYSV from infected tobacco leaves by using appropriate blocking buffer and proper concentration of biotin-labeled antibodies as well as the suitable ratio between the antibodies and the streptavidin R-phycoerythrin (SA-RPE). Under the optimized conditions the Luminex xMAP-based MIA was able to specifically detect IYSV with much higher sensitivity than conventional enzyme-linked immunosorbent assay (ELISA). Importantly, the Luminex xMAP-based MIA is time-saving and the whole procedure could be completed within 2.5 h. Conclusions We generated five specific MAbs against IYSV and developed the Luminex xMAP-based MIA method for specific detection of IYSV in plants. This assay provides a sensitive, high-specific, easy to perform and likely cost-effective approach for IYSV detection from infected plants, implicating potential broad usefulness of MIA in plant virus diagnosis

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used