Antibody, cell-mediated response and infection susceptibility in allogeneic hematopoietic stem cell recipients after COVID-19 mRNA vaccination.

BACKGROUND: Patients undergoing allogeneic stem-cell transplantation (allo-SCT) have reduced responses to vaccines due to immunosuppressive status linked to GvHD prophylaxis and treatment. In our study, we compared humoral responses to anti-SARS-CoV-2 mRNA vaccine, and infection onset, according to patients and transplant features; we also evaluated cellular response in patients without seroconversion. METHODS: We tested antibodies titer after second and third vaccine doses. Antibodies were detected through an immune-enzymatic assay. In a patients' subgroup without seroconversion, we tested cell-mediated responses evaluating interferon-gamma release by T-lymphocytes exposed to virus spike protein. RESULTS: Seroconversion rate increased from 66% at 30 days to 81% at 90 days after the second dose; it was 97% at 150 days after the third dose. We found a significant association between seroconversion after the second dose and two variables: shorter interval between allo-SCT and vaccination; ongoing immunosuppression. Twelve of 19 patients (63%) without antibodies after the second dose did not show cellular responses. Nineteen percent of patients developed SARS-CoV-2 infection after the third dose, with favorable outcome in all cases. Patients within 12 months after allo-SCT showed a significantly higher infection risk. CONCLUSIONS: Our study suggests that an interval shorter than 12 months between allo-SCT and first vaccine dose and/or ongoing immunosuppression were associated with humoral and cellular response deficiency after two doses. Third dose induced an increased and sustained humoral response in the majority of patients. However, patients within 1 year after allo-SCT remained at higher infection risk and may be candidate for prophylaxis with anti-SARS-CoV-2 monoclonal antibodies.

Immunogenicity and safety of a third dose of anti-SARS-CoV-2 BNT16b2 vaccine in liver transplant recipients.

BACKGROUND & AIMS: A strategy to improve the low rate of anti-SARS-CoV-2 mRNA vaccine-induced immunogenicity in liver transplant recipients (LTs) is urgently needed. METHODS: We analysed the rate of positive (≥0.8 U/ml) anti-SARS-CoV-2 receptor domain-binding protein (RBD) antibody response 2 months after a third dose of the BNT16b2 vaccine in 107 LTs who completed the second vaccine dose 7 months earlier. RESULTS: A positive anti-SARS-CoV-2-s-RBD antibody response after the third vaccine dose was detected in 98 (91.6%) LTs compared to 82 (76.6%) after the second vaccine dose (p = .003). The median of anti-SARS-CoV-2 RBD antibody titres increased from 22.9 U/ml 6 months after the second to 3500 U/ml 2 months after the third vaccine dose (p < .001). Fourteen (14.3%) responder patients presented antibody titres <100 U/ml, 57 (58.2%) between 100 and 9999 U/ml and 27 (27.6%) ≥10 000 U/ml. Seropositivity after the second dose was maintained after the third dose. Independent predictors of antibody response failure after the third vaccine dose were taking a higher daily dose of mycophenolate mofetil (MMF, p < .001) and had a lower (<60 ml/min/1.73 m2 ) estimated glomerular filtration rate (p = .007). Nine (9.1%) LTs experienced symptomatic SARS-CoV-2 infection after the third vaccine dose. Median antibody titres were not statistically different between infected and not infected LTs (1325 vs 3515 U/ml, p = .678). CONCLUSIONS: The third dose of the BNT16b2 vaccine increased the number of LTs who developed a positive anti-SARS-CoV-2 s-RBD antibody response. A proportion of patients remained unresponsive, mainly for modifiable factors, such as the use of MMF or multiple immunosuppressants.

Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients.

BACKGROUND & AIMS: The long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls. METHODS: LT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose. RESULTS: One hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively. CONCLUSIONS: In COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients. LAY SUMMARY: The immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.

Peer education for medical students on health promotion and clinical risk management.

CONTEXT: Health promotion (HP) and clinical risk management (CRM) topics are seldom discussed during medical school lessons. Peer-assisted learning (PAL) has long occurred informally in medical education, and interest in this method has recently grown, as it is considered a valuable technique for both tutors and tutees. AIMS: The aim was to evaluate the impact of HP and CRM PAL intervention on medical students' (tutees) knowledge level. SETTINGS AND DESIGN: A PAL intervention has been implemented at Udine University medical school during 2017. It was composed of lectures and practical activities conducted by ten near-peer tutors. METHODS: The effectiveness has been evaluated by giving tutees: (1) a knowledge multiple-choice questionnaire, before and after the intervention; (2) a satisfaction questionnaire; and evaluating (3) tutees' group assignments. STATISTICAL ANALYSIS USED: We performed descriptive analysis; then McNemar, Wilcoxon signed rank, Wilcoxon Mann-Whitney, and t-tests were applied. RESULTS: The number of students addressed by PAL intervention was 62. Difference in total correct answers among pre- and post-intervention questionnaires showed a statistically significant improvement (P < 0.0001), both when analyzing it globally and by area (HP/CRM). Students' satisfaction for CRM was greater than for HP area (P = 0.0041). CONCLUSIONS: This educational intervention based on PAL showed its effectiveness producing a statistically significant improvement in students' knowledge. Our findings confirm that PAL could be a feasible method for HP and CRM topics.

Professional attitudes toward incident reporting: can we measure and compare improvements in patient safety culture?

OBJECTIVE: To establish categories of professionals' attitudes toward incident reporting by analyzing the trends in incident reporting while accounting for general risk indicators. DESIGN: The incident reporting system was evaluated over 6 years. Reporting rates, stratified by year and profession, were estimated using the non-mandatory reported events/full-time equivalent (NM-IR/FTE) rate. Other indicators were collected using the hospital's official database. Staff attitudes toward self-reporting were analyzed. Univariate and multivariable analyses were performed. SETTING: A 1000-bed Italian academic hospital. PARTICIPANTS: Staff of the hospital (over 3200 professionals). INTERVENTIONS: None. MAIN OUTCOME MEASURES: NM-IT/FTE rates, self-reported rates, patient complaints/praises, work accidents among professionals and 30-day readmissions. RESULTS: The overall reporting rate was 0.44 (95% confidence interval [CI]: 0.42-0.46) among doctors and 0.40 (95% CI: 0.39-0.41) among nurses. Between 2010 and 2015, only the doctors' reporting rate increased significantly (P = 0.04), from 0.29 (95% CI: 0.25-0.34) to 0.67 (95% CI: 0.60-0.73). Patient complaints decreased from 384 to 224 (P < 0.001) and work accidents decreased from 296 to 235 (P = 0.01), while other indicators remained constant. Multivariable logistic regression showed that self-reporting was more likely among nurses than doctors (odds ratio: 1.51; 95% CI: 1.31-1.73) and for severe events than near misses (odds ratio: 1.78; 95% CI: 1.11-2.87). CONCLUSIONS: Because the doctors' reporting rates increased during the study period, doctors may be more likely to report adverse events than nurses, although nurses reported more events. Incident reporting trends and other routinely collected risk indicators may be useful to improve our understanding and measurement of patient safety issues.