Association between sex hormones and anti-S/RBD antibody responses to COVID-19 vaccines in healthcare workers.

Healthcare workers (HCWs) are the target population for vaccination against coronavirus disease (COVID-19) as they are at a high risk of exposure and transmission of pathogens to patients. Neutralizing antibodies developed after COVID-19 vaccination decline within few months of vaccination. Several factors, including age and sex, can affect the intensity, efficacy, and duration of immune response to vaccines. However, sex-specific analyses of humoral responses to COVID-19 vaccines are lacking. This study aimed to evaluate sex-based differences in anti-S/RBD (Receptor Binding Domain) responses at three different time points after the second dose of mRNA COVID-19 vaccine in HCWs in relation to age, and to investigate the role of sex hormones as potential markers of response. Anti-S/RBD levels after two doses of the mRNA vaccine were collected from 521 HCWs naïve to COVID-19, working at two Italian Clinical Centers. Multiple regression analysis was applied to evaluate the association between anti-S levels and sex, age, and plasma levels of sex hormones. Significantly higher anti-S/RBD response to the COVID-19 vaccination was found in female HCWs, and a significant and more abrupt decline in response with time was observed in women than that in men. A novel, positive association of testosterone plasma levels and higher anti-S levels in male HCWs was found, suggesting its potential role as sex specific marker in males. In conclusion, understanding the sex-based differences in humoral immune responses to vaccines may potentially improve vaccination strategies and optimize surveillance programs for HCWs.

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.

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.

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.

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.

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.

Repeated vaccinations do not improve specific immune defenses against Hepatitis B in non-responder health care workers.

Hepatitis B is a major infectious occupational hazard for health care workers and can be prevented with a safe and effective vaccine. The serum titer of anti-HBsAg antibodies is the most commonly used correlate of protection and post-vaccination anti-HBsAg concentrations of ≥ 10 mIU/ml are considered protective. Subjects with post-vaccination anti-HBsAg titers of <10 mIU/ml 1-6 months post-vaccination, who tested negative for HBsAg and anti-HBc, are defined as non-responders. The question of whether non-responders should be repeatedly vaccinated is still open. The aim of the study was to (i) evaluate the distribution of lymphocyte subpopulations and the percentage of HBsAg-specific memory B cells in responders and non-responders (ii) assess whether non-responders can be induced to produce antibodies after administration of a booster dose of vaccine (iii) determine whether booster vaccination increases the number of specific memory B cells in non-responders. Combining flow-cytometry, ELISPOT and serology we tested the integrity and function of the immune system in 24 health care workers, confirmed to be non-responders after at least three vaccine injections. We compared the results with those obtained in 21 responders working in the same institution. We found that the great majority of the non-responders had a functional immune system and a preserved ability to respond to other conventional antigens. Our most important findings are that the frequency of HBsAg-specific memory B cells is comparable in non-responders and controls and that booster immunization does not lead either to antibody production or memory B cell increase in non-responders.

PTSD prevalence and associated risk factors after a fire disaster that broke out in a paediatric hospital: a cross-sectional study.

BACKGROUND: Several studies have shown a higher risk of psychological problems in health care workers exposed to serious occupational stressors. OBJECTIVES: The aim of the present study was to assess the presence of Post-traumatic Stress Disorder (PTSD) and possible risk factors in a sample of 32 workers who were at the same time rescuers and victims of a fire that broke out in the neonatal intensive care unit of a large paediatric hospital. METHODS: Immediately and six months after the event, the subjects underwent a study protocol aimed at the diagnostic assessment of PTSD, investigated via the Clinician-Administered PTSD Scale (CAPS) and the Impact of Event Scale-Revised (IES-R). RESULTS: Out of the 30 subjects examined (two were missing), six showed the diagnostic criteria for a current PTSD. Risk factors for PTSD onset were a prior psychiatric disorder, the level of involvement in the fire disaster and the presence of phobias in the days immediately after the event. Gender and level of education approached statistical significance. CONCLUSIONS: The high prevalence of PTSD found in this sample was due to the fact that the risk of death or serious injury involved infants.

Accidental exposure to UV radiation produced by germicidal lamp: case report and risk assessment.

Ultraviolet radiation is known to cause both benefits and harmful effects on humans. The adverse effects mainly involve two target organs, skin and eye, and can be further divided into short- and long-term effects. The present case report describes an accidental exposure of two health-care workers to ultraviolet radiation produced by a germicidal lamp in a hospital pharmacy. The germicidal lamp presented a spectrum with an intense UV-C component as well as a modest UV-B contribution. Overexposure to UV-C radiation was over 100 times as large as the ICNIRP exposure limits. A few hours after the exposure, the two subjects reported symptoms of acute UV injury and both of them continued having significant clinical signs for over 2 years. In this study, we describe acute and potentially irreversible effects caused by high UV exposure. In addition, we present the results of risk assessment by occupational exposure to germicidal lamps.