Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections.

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3-4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen.

Personalized profiles of antioxidant signaling pathway in patients with tuberculosis.

BACKGROUND/PURPOSE: The non-protein thiol glutathione is protective against infection by Mycobacterium tuberculosis (MTB) and, together with the transcription factor NRF2 (the nuclear factor erythroid 2-related factor 2), plays a crucial role in counteracting MTB-induced redox imbalance. Many genes implicated in the antioxidant response belong to the NRF2-signalling pathway, whose central role in the pathogenesis of tuberculosis (TB) has been recently proposed. METHODS: In this study, we measured GSH levels in blood of patients with active TB and analysed the individual NRF2-mediated redox profile, in order to provide additional tools for discriminating the pathologic TB state and addressing therapeutic interventions. RESULTS: Our findings show a systemic individual modulation of GSH and NRF2 signaling pathway in patients with TB, with a "personalized" induction of NRF2-target genes. CONCLUSION: This study can provide useful tools to monitor the course of the infection and address patients' treatment.

Highly Specific Memory B Cells Generation after the 2nd Dose of BNT162b2 Vaccine Compensate for the Decline of Serum Antibodies and Absence of Mucosal IgA.

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.

Evolution of Human Memory B Cells From Childhood to Old Age.

High quality medical assistance and preventive strategies, including pursuing a healthy lifestyle, result in a progressively growing percentage of older people. The population and workforce is aging in all countries of the world. It is widely recognized that older individuals show an increased susceptibility to infections and a reduced response to vaccination suggesting that the aged immune system is less able to react and consequently protect the organism. The SARS-CoV-2 pandemic is dramatically showing us that the organism reacts to novel pathogens in an age-dependent manner. The decline of the immune system observed in aging remains unclear. We aimed to understand the role of B cells. We analyzed peripheral blood from children (4-18 years); young people (23-60 years) and elderly people (65-91 years) by flow cytometry. We also measured antibody secretion by ELISA following a T-independent stimulation. Here we show that the elderly have a significant reduction of CD27dull memory B cells, a population that bridges innate and adaptive immune functions. In older people, memory B cells are mostly high specialized antigen-selected CD27bright. Moreover, after in vitro stimulation with CpG, B cells from older individuals produced significantly fewer IgM and IgA antibodies compared to younger individuals. Aging is a complex process characterized by a functional decline in multiple physiological systems. The immune system of older people is well equipped to react to often encountered antigens but has a low ability to respond to new pathogens.

Return on Investment (ROI) and Development of a Workplace Disability Management Program in a Hospital-A Pilot Evaluation Study.

The progressive ageing of the working population and the increase in related chronic diseases tend to affect working capacity. The aim of this study was to evaluate a Workplace Disability Management Program (WDMP) within a pediatric hospital. Absenteeism due to healthcare workers' (HCWs) pre- and post- WDMP and the related costs were used for the program evaluation. The Return on Investment (ROI), the Break-Even Analysis (BEA) and the value of the average annual productivity of HCWs who took advantage of the Disability Management (DM) interventions to assess the economic impact of the program, were also used. The HCWs enrolled in the program were 131 (approximately 4% of hospital staff), of which 89.7% females and with an average age of 50.4 years (SD ± 8.99). Sick leave days of the HCWs involved decreased by 66.6% in the year following the end of WDMP compared to the previous one (p < 0.001). The total estimated cost reduction of absenteeism is 427,896€ over a year. ROI was equal to 27.66€. BEA indicated that the break-even point was reached by implementing the program on 3.27 HCWs. The program evaluation demonstrated the particular effectiveness of the implemented WDMP model, acting positively on the variables that affect productivity and the limitation to work.

Sex Disparity in Response to Hepatitis B Vaccine Related to the Age of Vaccination.

Hepatitis B virus (HBV) infection is one of the major infectious hazards for health-care workers (HCWs) because of the frequency of percutaneous exposures to blood or body fluids. For this reason, all HCWs should be vaccinated, including students in medicine and health professional degree programs. The aim of this study was to assess the immune coverage to anti-HBV vaccine and long-lasting protective titres of anti-HBs antibodies in female and male students to evaluate gender-related differences in response to HBV vaccination. Data relative to anti-HBs antibody titre, sex, age, and age at vaccination were collected and analyzed from 5291 Italian students (1812 males and 3479 females) of the graduate courses at the School of Medicine, who underwent the mandatory health surveillance of workers exposed to biological risk. The results indicated that gender affects the immune response to HBV vaccine, particularly evident in the case of females vaccinated after one year of age who exhibited a statistically significant (p = 0.0023) 1.21-fold increase in median antibody titre with respect to males. Our findings could contribute to the optimization of HBV vaccination schedules in health surveillance of HCWs.

Seasonal influenza vaccination and absenteeism in health-care workers in two subsequent influenza seasons (2016/17 and 2017/18) in an Italian pediatric hospital.

BACKGROUND: Seasonal influenza in Health-Care Workers (HCWs) is a topic of growing interest in public health for its organizational implications. The study aims at measuring absenteeism due to influenza in HCWs of an Italian pediatric hospital. RESEARCH DESIGN AND METHODS: A retrospective observational study on absenteeism for influenza and influenza-like illness was carried out on all hospital HCWs. Sickness absences up to 5 days and vaccination status of HCWs were recorded during the last two years (2016/2017, 2017 /2018). Average sickness absenteeism rate in vaccinated and unvaccinated HCWs and total working days lost were estimated. Daily mean cost for HCW was calculated in order to define the non-vaccination costs. RESULTS: In this study, the authors analyzed the overlapping between the trend of weekly sickness absenteeism and the morbidity rate associated with influenza epidemics in adults living in the Lazio region, Italy. An excess of 0.38 (p = 0.03) and 0.46 (p = 0.01) of average days lost was recorded in unvaccinated HCWs in the 2016/2017 and 2017/2018 epidemic seasons. The total amount of days lost in unvaccinated HCWs is 1.485,4 with a total cost of € 252.060,54. CONCLUSIONS: Seasonal influenza vaccination confirms its key role in preventing outbreaks of influenza and promoting HCWs health.

Seasonal Influenza Vaccination in Health Care Workers. A Pre-Post Intervention Study in an Italian Paediatric Hospital.

Despite relevant recommendations and evidences on the efficacy of influenza vaccination in health care workers (HCWs), vaccination coverage rates in Europe and Italy currently do not exceed 25%. Aim of the study is to measure the variations in vaccination coverage rates in an Italian pediatric hospital after a promotion campaign performed in the period October⁻December 2017. The design is a pre-post intervention study. The intervention is based on a wide communication campaign and an expanded offer of easy vaccination on site. The study was carried out at Bambino Gesù Children’s hospital in Rome, Italy, on the whole population of HCWs. Univariate and multivariate statistical analyses were performed. Vaccination coverage rate increased in 2017/18 campaign compared with the 2016/17 one (+95 HCWs vaccinated; +4.4%). The highest increases were detected in males (+45.7%), youngest employees (+142.9%), mean age of employment (+175%), other HCWs (+209.1%), Emergency Area (+151.6%) and Imaging Diagnostic Department (+200.0%). At multivariate logistic regression, working in some departments and being nurses represents a higher risk of being unvaccinated. Although the vaccination coverage rate remained low, a continuous increase of the coverage rate and development of a different consciousness in HCWs was highlighted. The study significantly identified the target for future campaigns.