Redox biomarkers in asymptomatic latent human tuberculosis: a comparison with active disease.

BACKGROUND: The latent TB infection (LTBI) is an asymptomatic infection caused by Mycobacterium tuberculosis (M.bt). Previous studies have shown a host-protective role for Heme oxygenase-1 (HO-1) during Mtb infection and an important involvement of Glutathione peroxidase-4 (Gpx4) in the necrotic pathology of the disease. Furthermore, increasing evidence suggested a crucial role for Glutathione in the granulomatous response to M. tb infection, with altered GSH levels associated to decreased host resistance. The aim of this study was to provide additional tools for discriminating the pathologic TB state and the asymptomatic infection. METHODS: We analyzed the gene expression of HO-1 and Gpx4 enzymes in blood of subjects with LTBI, active TB and healthy controls, and we also measured blood levels of the reduced (GSH) and oxidized (GSSG) forms of glutathione, together with the evaluation of GCL expression, the gene responsible for the GSH de novo synthesis. RESULTS: Our findings highlight a shift of glutathione homeostasis towards a more reducing conditions in LTBI, and a different modulation of GSH-dependent genes and HO-1 expression respect to active TB. CONCLUSION: This study can provide useful tools to understand the redox background that address the infection toward the asymptomatic or active disease.

Feasibility of a Stop Smoking Program for Healthcare Workers in an Italian Hospital: Econometric Analysis in a Total Worker Health® Approach.

Background: Over 20% of healthcare workers (HCWs) are active smokers. Smoking is a targeted issue for workplace health promotion (WHP) programs. Objective: Our study aims to evaluate the effectiveness of the Stop Smoking Promotion (SSP) intervention, a 6-hour training course for HCWs, which took place from May 2018 to July 2019. Methods: We compared HCWs who successfully quit smoking (n = 15) to those who did not (n = 25) in terms of Sickness Absence Days (SADs). Moreover, we conducted an econometric analysis by calculating the return on investment and implementing a break-even analysis. Findings: Among the 40 enrolled workers, a success rate of 37.5% was observed after a span of over two years from the SSP intervention (with nurses and physicians showed the best success rate). Overall, participants showed a noticeable absenteeism reduction after the SSP intervention, with a reduction rate of 85.0% in a one-year period. The estimated ROI for the hospital was 1.90, and the break-even point was 7.85. In other words, the organization nearly doubled its profit from the investment, and the success of at least eight participants balanced costs and profits. Conclusion: Our pilot study confirms that WHP programs are simple and cost-saving tools which may help improve control over the smoking pandemic in healthcare settings.

SARS-CoV-2 Breakthrough Infections According to the Immune Response Elicited after mRNA Third Dose Vaccination in COVID-19-Naïve Hospital Personnel.

BACKGROUND: Vaccine-induced SARS-CoV-2-anti-spike antibody (anti-S/RBD) titers are often used as a marker of immune protection and to anticipate the risk of breakthrough infections, although no clear cut-off is available. We describe the incidence of SARS-CoV-2 vaccine breakthrough infections in COVID-19-free personnel of our hospital, according to B- and T-cell immune response elicited one month after mRNA third dose vaccination. METHODS: The study included 487 individuals for whom data on anti-S/RBD were available. Neutralizing antibody titers (nAbsT) against the ancestral Whuan SARS-CoV-2, and the BA.1 Omicron variant, and SARS-CoV-2 T-cell specific response were measured in subsets of 197 (40.5%), 159 (32.6%), and 127 (26.1%) individuals, respectively. RESULTS: On a total of 92,063 days of observation, 204 participants (42%) had SARS-CoV-2 infection. No significant differences in the probability of SARS-CoV-2 infection for different levels of anti-S/RBD, nAbsT, Omicron nAbsT, or SARS-CoV-2 T cell specific response, and no protective thresholds for infection were found. CONCLUSIONS: Routine testing for vaccine-induced humoral immune response to SARS-CoV-2 is not recommended if measured as parameters of 'protective immunity' from SARS-CoV-2 after vaccination. Whether these findings apply to new Omicron-specific bivalent vaccines is going to be evaluated.

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.

The Management of Workplace Violence against Healthcare Workers: A Multidisciplinary Team for Total Worker Health® Approach in a Hospital.

The risk of aggression against healthcare workers (HCWs) is a globally well-known topic. However, workplace violence (WV) is often considered as part of HCW's job, leading to a general underreporting. This cross-sectional study aims at providing a descriptive analysis of aggressive acts against HCWs registered in a 34-month period in a pediatric hospital. According to a specific protocol, each aggressive act was analyzed by a multidisciplinary team using the "Modified Overt Aggression Scale" (MOAS), the "General Health Questionnaire-12" (GHQ-12), and the "Short Form-36 Health Survey" (SF-36) to build a report addressing improvement measures. A three-domain model of WV was also developed considering: (1) assaulted HCWs, (2) attacker-related issues, and (3) environmental context. Contributing factors to overt aggression were outlined and tested using univariate analyses. Statistically significant factors were then included in a multiple linear regression model. A total of 82 aggressive acts were registered in the period. MOAS scores registered a mean value of 3.71 (SD: 4.09). Verbal abuse was the most common form of WV. HCWs professional category, minor psychiatric disorder, emotional role limitation, type of containment used, and emotion intensity were significantly associated with overt aggression (p < 0.05), as well as the attacker's role in the hospital (p < 0.05). The multiple regression analysis confirmed these findings (p < 0.001). Raising awareness on the aggression risk and contributing factors may lead to a relevant improvement of workplace environment, individual workers' health, and organizational well-being.

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.

Recurrence, Reactivation, or Inflammatory Rebound of SARS-CoV-2 Infection With Acute Vestibular Symptoms: A Case Report and Revision of Literature.

A case of recurrent coronavirus disease 2019 (COVID-19) with neurovestibular symptoms was reported. In March 2020, a physician working in an Italian pediatric hospital had flu-like symptoms with anosmia and dysgeusia, and following a reverse transcription PCR (RT/PCR) test with a nasopharyngeal swab tested positive for SARS-CoV-2. After home quarantine, 21 days from the beginning of the symptoms, the patient tested negative in two subsequent swabs and was declared healed and readmitted to work. Serological testing showed a low level of immunoglobulin G (IgG) antibody title and absence of immunoglobulin M (IgM). However, 2 weeks later, before resuming work, the patient complained of acute vestibular syndrome, and the RT/PCR test with mucosal swab turned positive. On the basis of the literature examined and reviewed for recurrence cases and vestibular symptoms during COVID-19, to our knowledge this case is the first case of recurrence with vestibular impairment as a neurological symptom, and we defined it as probably a viral reactivation. The PCR retest positivity cannot differentiate re-infectivity, relapse, and dead-viral RNA detection. Serological antibody testing and viral genome sequencing could be always performed in recurrence cases.

Effectiveness of Psychological Support to Healthcare Workers by the Occupational Health Service: A Pilot Experience.

Work-related stress is a significant risk for healthcare workers (HCWs). This study aims at evaluating the effectiveness of an individual psychological support programme for hospital workers. In all, 35 workers participated (n). A control group of 245 workers (7n) was set. Occupational distress was measured by the General Health Questionnaire, (GHQ-12), the quality of life by the Short Form-36 health survey, (SF-36), and sickness absence was recorded. Costs and benefits of the service were evaluated and the return on investment (ROI) was calculated. The level of distress was significantly reduced in the treated group at the end of the follow-up (p < 0.001). Quality of life had significantly improved (p < 0.003). A 60% reduction of sickness absence days (SADs) following the intervention was recorded. After the treatment, absenteeism in cases was significantly lower than in controls (p < 0.02). The individual improvement of mental health and quality of life was significantly correlated with the number of meetings with the psychologist (p < 0.01 and p < 0.03, respectively). The recovery of direct costs due to reduced sick leave absence was significantly higher than the costs of the programme; ROI was 2.73. The results must be examined with caution, given the very limited number of workers treated; this first study, however, encouraged us to continue the experience.

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.

Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases.

SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focused on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. In order to understand the basis of the protective immune response in COVID-19, we performed a longitudinal follow-up, flow-cytometric and serological analysis of innate and adaptive immunity in 64 adults with a spectrum of clinical presentations: 28 healthy SARS-CoV-2-negative contacts of COVID-19 cases; 20 asymptomatic SARS-CoV-2-infected cases; eight patients with Mild COVID-19 disease and eight cases of Severe COVID-19 disease. Our data show that high frequency of NK cells and early and transient increase of specific IgA, IgM and, to a lower extent, IgG are associated with asymptomatic SARS-CoV-2 infection. By contrast, monocyte expansion and high and persistent levels of IgA and IgG, produced relatively late in the course of the infection, characterize severe disease. Modest increase of monocytes and different kinetics of antibodies are detected in mild COVID-19. The importance of innate NK cells and the short-lived antibody response of asymptomatic individuals and patients with mild disease suggest that only severe COVID-19 may result in protective memory established by the adaptive immune response.

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.