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

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (&lt;380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

Forecasting aortic aneurysm rupture: a systematic review of seasonal and atmospheric associations

Background: Abdominal aortic aneurysms (AAAs) represent a significant burden of disease worldwide, and their rupture, without treatment, has an invariably high mortality rate. Whereas some risk factors for ruptured AAAs (rAAAs) are well established, such as hypertension, smoking, and female sex, the impact of seasonal and meteorologic variables is less clear. We systematically reviewed the literature to determine whether these variables are associated with rAAA. Methods: Review methods were according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We calculated pooled proportions and incidence rate ratios (IRRs) for the different months and seasons. Funnel plots were constructed to assess for publication bias. Given the poor methodologic quality of included studies, a sensitivity analysis was performed on better-quality studies, which scored 6 and above of 9 in the author-modified Newcastle-Ottawa Scale. Results: The pooled proportion of rAAA was highest in the autumn season (incidence rate, 26.6%; 95% confidence interval [CI], 25.6%-27.7%; I = 15.4%), followed by winter (incidence rate, 26.2%; 95% CI, 24.1%-28.2%; I = 72.4%), and lowest in summer (incidence rate, 21.1%; 95% CI, 19.3%-23.0%; I = 70.4%). The IRRs of rAAA were −6.9% (95% CI, −9.8% to −3.9%), −19.5% (95% CI, −22% to −16.8%), +10.5% (95% CI, 7.2%-13.9%), and +18.1% (95% CI, 15%-22%) in spring, summer, autumn, and winter compared with the remaining seasons, respectively (all P < .0001), thus affirming existence of seasonal variation. The pooled proportion of rAAA was highest in December (incidence rate, 8.9%; 95% CI, 7.1%-10.9%; I = 54.5%) but lowest in July (incidence rate, 5.7%; 95% CI, 4.2%-7.3%; I = 54.5%). The IRR was significantly the highest in January (IRR, 1.14; 95% CI, 1.01-1.29; P = .031) but lowest in July (IRR, 0.75; 95% CI, 0.65-0.87; P < .0001). There is also some evidence for a possible association with atmospheric pressure. Associations with temperature and daylight hours, however, are at best speculative. Conclusions: Autumn and winter are significantly associated with a higher incidence of rAAAs, and autumn is associated with the highest rupture incidence of all the seasons. However, the inability to appropriately control for other confounding factors known to increase the risk of AAA rupture precludes any additional recommendations to alter current provision of vascular services on the basis of these data

Direct Comparison of Cardiac Myosin-Binding Protein C with Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction

Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI.Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality.Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (-1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

National study of NAFLD management identifies variation in delivery of care in the UK between 2019 to 2022

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with liver and cardiovascular morbidity and mortality. Recently published NAFLD Quality Standards include 11 key performance indicators (KPIs) of good clinical care. This national study, endorsed by British Association for the Study of the Liver (BASL) and British Society of Gastroenterology (BSG), aimed to benchmark NAFLD care in UK hospitals against these KPIs. Methods: This study included all new patients with NAFLD reviewed in the outpatient clinic in the months of March 2019 and March 2022. Participating UK hospitals self-registered for the study through BASL/BSG. KPI outcomes were compared using Fisher's exact or Chi-square tests. Results: Data from 776 patients with NAFLD attending 34 hospitals (England [25], Scotland [four], Wales [three], Northern Ireland [two]) were collected. A total of 85.3% of hospitals reported established local liver disease assessment pathways, yet only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment documented at the point of referral to secondary care. In secondary care, 79.1% of patients had fibrosis assessment. Assessment of cardiometabolic risk factors including obesity, type 2 diabetes, hypertension, and smoking were conducted in 73.2%, 33.0%, 19.3%, and 54.9% of all patients, respectively. There was limited documentation of diet (35.7%) and exercise advice (55.1%). Excluding those on statins, only 9.1% of patients with NAFLD at increased cardiovascular risk (T2DM and/or QRISK-3 >10%) had documented discussion of statin treatment. Significant KPI improvements from 2019 to 2022 were evident in use of non-invasive fibrosis assessment before secondary care referral, statin recommendations, and diet and exercise recommendations. Conclusions: This national study identified substantial variation in NAFLD management in the UK with clear areas for improvement, particularly fibrosis risk assessment before secondary care referral and management of associated cardiometabolic risk factors. Impact and implications: This study identified significant variation in the management of NAFLD in the UK. Only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment performed to identify those at greater risk of advanced liver disease before specialist referral. Greater emphasis is needed on the management of associated cardiometabolic risk factors in individuals with NAFLD. Hospitals with multidisciplinary NAFLD service provision had higher rates of fibrosis evaluation and assessment and management of cardiometabolic risk than hospitals without multidisciplinary services. Further work is needed to align guideline recommendations and real-world practice in NAFLD care