Humoral and T-cell-mediated immunity to SARS-CoV-2 vaccination in patients with liver disease and transplant recipients.

BACKGROUND: SARS-CoV-2 vaccination induces a varied immune response among persons with chronic liver disease (CLD) and solid organ transplant recipients (SOTRs). We aimed to evaluate the humoral and T-cell-mediated immune responses to SARS-CoV-2 vaccination in these groups. METHODS: Blood samples were collected following the completion of a standard SARS-CoV-2 vaccination (2 doses of either BNT162b2 or mRNA-12732), and a subset of patients had a blood sample collected after a single mRNA booster vaccine. Three separate methods were utilized to determine immune responses, including an anti-spike protein antibody titer, neutralizing antibody capacity, and T-cell-mediated immunity. RESULTS: The cohort included 24 patients with chronic liver disease, 27 SOTRs, and 9 controls. Patients with chronic liver disease had similar immune responses to the wild-type SARS-CoV-2 compared with controls following a standard vaccine regimen and single booster vaccine. SOTRs had significantly lower anti-S1 protein antibodies (p < 0.001), neutralizing capacity (p < 0.001), and T-cell-mediated immunity response (p = 0.021) to the wild-type SARS-CoV-2 compared with controls following a standard vaccine regimen. Following a single booster vaccine, immune responses across groups were not significantly different but numerically lower in SOTRs. The neutralization capacity of the B.1.1.529 Omicron variant was not significantly different between groups after a standard vaccine regimen (p = 0.87) and was significantly lower in the SOTR group when compared with controls after a single booster vaccine (p = 0.048). CONCLUSION: The immunogenicity of the SARS-CoV-2 vaccine is complex and multifactorial. Ongoing and longitudinal evaluation of SARS-CoV-2 humoral and cellular responses is valuable and necessary to allow frequent re-evaluation of these patient populations.

Ghrelin stimulation of growth hormone isoforms: parallel secretion of total and 20-kDa growth hormone and relation to insulin sensitivity in healthy humans.

CONTEXT: The 20-kDa human GH (hGH) is produced in the pituitary by alternative splicing of the hGH-N gene. The 20-kDa hGH promotes growth similarly to 22-kDa or total hGH, the predominant form in circulation, but the relative effects of these isoforms on glucose metabolism have been debated. OBJECTIVE: To investigate the effect of ghrelin on 20-kDa and total hGH secretion in healthy, nonobese subjects. We also studied associations between basal GH concentration and fasting glucose and insulin as well as between dynamic GH secretion and insulin sensitivity. DESIGN AND SETTING: Synthetic human acyl ghrelin (0.2 or 0.6 nmol/kg · h) or saline was infused in random order in 14 healthy subjects (six males, eight females; age 27.7 ± 6.3 yr; body mass index 22.0 ± 2.7 kg/m(2), mean ± SEM) on 3 separate days. Ghrelin was infused for 45 min to achieve steady-state levels and continued through a 3-h frequently sampled i.v. glucose tolerance test. Insulin sensitivity index was quantified using the minimal model of glucose kinetics. RESULTS: Basal 20-kDa and total GH concentrations were 0.4 ± 0.1 and 2.2 ± 0.4 ng/ml, respectively, with a 20-kDa to total GH ratio of 0.13 ± 0.02. Females had significantly higher baseline GH levels. Ghrelin administration increased 20-kDa and total GH levels in a parallel and dose-dependent fashion, with no significant change in the ratio of the isoforms. Basal 20-kDa and total GH levels were negatively correlated with fasting glucose, insulin, and homeostasis model assessment of insulin resistance. During the frequently sampled iv glucose tolerance test, GH secretion was positively correlated with insulin sensitivity index with saline infusion. CONCLUSION: Ghrelin dose-dependently increases endogenous 20-kDa and total GH secretion in a parallel fashion in healthy subjects. Both basal and stimulated levels of the different GH isoforms were positively associated with insulin sensitivity in this cohort of healthy men and women.

Sex, aging, and preexisting cerebral ischemic disease in patients with aortic stenosis.

BACKGROUND: Patients undergoing cardiac surgery have a high frequency of preexisting cerebral ischemic lesions, the presence of which appears to predict cognitive sequelae. Patients undergoing aortic valve replacement for aortic stenosis (AS) incur an exceptionally high risk for perioperative cerebral ischemia. The extreme risk in this subgroup may arise from the preexisting burden of cerebral ischemic disease. We tested the hypotheses that increasing age, female sex, coronary artery disease, and the severity of AS are predictive of the severity of preexisting cerebral ischemic lesions. METHODS: A total of 95 subjects were included in this study. Subjects were imaged on 1.5 Tesla magnetic resonance imaging scanners to obtain multimodal image sets which were used for the automatic segmentation of cerebral lesion volume. The dependence of lesion volume upon age, sex, coronary artery disease, and the severity of AS were tested. RESULTS: The results demonstrate a strong correlation between aging, female sex, and white matter and ischemia-like lesion volume in patients with aortic stenosis. CONCLUSIONS: Women and those of advanced age presenting for aortic valve replacement for AS may incur a particularly high risk for postoperative neurologic sequelae due to an exceptional preexisting burden of cerebral ischemic disease.