Interleukin-2-mediated CD4 T-cell activation correlates highly with effective serological and T-cell responses to SARS-CoV-2 vaccination in people living with HIV.

People living with HIV (PLWH) despite having an appreciable depletion of CD4+ T-cells show a good severe acute respiratory syndrome coronavirus 2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T-cell responses in PLWH receiving anti-retroviral therapy stratified on CD4+ counts as PLWH-high (CD4 ≥ 500 cells/mm3) and PLWH-low (<500 cells/mm3). Responses were assessed longitudinally before the first vaccination (T0), 1-month after the first dose (T1), 3-months (T2), and 6-months (T3) after the second dose. Expectedly, both PLWH-high and -low groups developed similar serological responses after T2, which were also non-significantly different from age and vaccination-matched HIV-negative controls at T3. The immunoglobulin G titers were also protective showing a good correlation with angiotensin-converting enzyme 2-neutralizations (R = 0.628, p = 0.005). While surface and intracellular activation analysis showed no significant difference at T3 between PLWH and controls in activated CD4+CD154+ and CD4+ memory T-cells, spike-specific CD4+ polyfunctional cytokine expression analysis showed that PLWH preferentially express interleukin (IL)-2 (p < 0.001) and controls, interferon-γ (p = 0.017). CD4+ T-cell counts negatively correlated with IL-2-expressing CD4+ T-cells including CD4+ memory T-cells (Spearman ρ: -0.85 and -0.80, respectively; p < 0.001). Our results suggest that the durable serological and CD4+ T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4+ T-cell activation that likely compensates for CD4+ T-cell depletion in PLWH.

SARS-CoV-2 Positivity in Foreign-Born Adults: A Retrospective Study in Verona, Northeast Italy.

We compared SARS-CoV-2 positivity between the foreign-born adult working population and Italians living in the Verona area to investigate whether being a foreign-born adult could confer an increased risk of infection or lead to a diagnostic delay. The present study included 105,774 subjects, aged 18-65 years, tested for SARS-CoV-2 by nasopharyngeal swabs and analyzed at the University Hospital of Verona between January 2020 and September 2022. A logistic regression model was used, controlling for gender, age, time of sampling, and source of referral. A higher proportion of SARS-CoV-2 positivity in Italian (30.09%) than in foreign-born (25.61%) adults was reported, with a higher proportion of SARS-CoV-2 positivity in men than women in both cohorts analyzed. The difference in swab positivity among Italian and foreign-born adults was the highest in people aged 18-29 years (31.5% vs. 23.3%) and tended to disappear thereafter. Swab positivity became comparable between Italian and foreign-born adults during the vaccination campaign. Multivariable analysis confirmed the lower risk of swab positivity among foreign-born adults (OR = 0.85, 95% CI 0.82-0.89). In the Verona area, foreign-born adults showed a lower rate of SARS-CoV-2 positivity than the native population, likely because of underdiagnosis. Hence, public health should increase attention toward these particularly vulnerable populations.

Protective role of SARS-CoV-2 anti-S IgG against breakthrough infections among European healthcare workers during pre and post-Omicron surge-ORCHESTRA project.

PURPOSE: Anti SARS-CoV-2 vaccination initially showed high effectiveness in preventing COVID-19. However, after the surge of variants of concern, the effectiveness dropped. Several studies investigated if this was related to the decrease of the humoral response over time; however, this issue is still unclear. The aim of this study was to understand whether SARS-CoV-2 anti-S IgG levels can be used to predict breakthrough infection risk and define the timing for further booster doses administration. METHOD: Within the framework of the ORCHESTRA Project, over 20,000 health workers from 11 European centers were enrolled since December 2020. We performed two Cox proportional hazards survival analyses regarding pre-Omicron (from January to July 2021) and Omicron (December 2021-May 2022) periods. The serological response was classified as high (above the 75th percentile), medium (25th-75th), or low (< 25th). RESULTS: Seventy-four (0.33%) and 2122 (20%) health workers were infected during the first and second periods, respectively. Both Cox analyses showed that having high anti-S titer was linked to a significantly lower risk of infection as compared to having medium serological response [HR of high vs medium anti-S titer = 0.27 (95% CI 0.11-0.66) during the first phase, HR = 0.76 (95% CI 0.62-0.93) during the second phase]. CONCLUSION: Vaccine effectiveness wanes significantly after new variants surge, making anti-S titer unsuitable to predict optimal timing for further booster dose administration. Studies on other immunological indicators, such as cellular immunity, are therefore needed to better understand the mechanisms and duration of protection against breakthrough infection risk.

Risk of obstructive sleep apnea among health workers: results of a screening in a large Italian University Hospital.

PURPOSE: Obstructive sleep apnea (OSA) is a common respiratory sleep disorder, related to increased mortality, poor quality of life, and higher risk of work accidents and injuries. Studies on the risk of OSA (rOSA) among health workers (HW) are scant. The aims of this study were to investigate this issue in a large University Hospital and to assess the effectiveness of a screening program. METHODS: The STOP-BANG questionnaire (SBQ) was sent via e-mail to the 5031 HW employed at the University Hospital of Verona. HW who completed the SBQ were classified at low, moderate, and high rOSA. HW at high rOSA were invited to undergo nocturnal polygraphy. The determinants of rOSA were studied by non-parametric Kruskal-Wallis test, Pearson's chi-squared, and multinomial logistic model. RESULTS: Of 5031 HW, 1564 (31.1%) completed the online questionnaire. Responders with low, moderate, and high rOSA were 72.7%, 13.7%, and 13.6%. Male gender, older age, and higher body mass index (BMI) were significant predictors of high rOSA, as expected. Physicians had the lowest probability of being in the high-risk category. Polygraphy was performed in 64 subjects. The positive predictive value of the self-administered SBQ was 68.8% (95%C.I. 55.9-79.8%) but raised to 96.9% (95%C.I. 89.2-99.6%) when re-administered by medical staff. CONCLUSION: SBQ showed its effectiveness as a screening tool in detecting undiagnosed OSA in HW. Systematic screening for OSA in work settings could allow early diagnosis and treatment, reducing short- and long-term health effects of OSA.

A Multi-Center Study Investigating Long COVID-19 in Healthcare Workers from North-Eastern Italy: Prevalence, Risk Factors and the Impact of Pre-Existing Humoral Immunity-ORCHESTRA Project.

Introduction: The impact of long-COVID-19 syndrome is rather variable, since it is influenced by several residual confounders. This study aimed to investigate the prevalence of long COVID-19 in healthcare workers (HCWs) from four university hospitals in north-eastern Italy: Trieste, Padua, Verona, and Modena-Reggio Emilia. Methods: During the period June 2022-August 2022, HCWs were surveyed for past COVID-19 infections, medical history, and any acute as well as post-COVID-19 symptoms. The prevalence of long COVID-19 was estimated at 30-60 days or 61+ days since first negative swab following first and second COVID-19 episode. Furthermore, the risk of long COVID-19 was investigated by multivariable logistic regression. Results were expressed as the adjusted odds ratio (aOR) with a 95% confidence interval (95%CI). Results: 5432 HCWs returned a usable questionnaire: 2401 were infected with SARS-CoV-2 at least once, 230 were infected at least twice, and 8 were infected three times. The prevalence of long COVID-19 after a primary COVID-19 infection was 24.0% at 30-60 days versus 16.3% at 61+ days, and 10.5% against 5.5% after the second SARS-CoV-2 event. The most frequent symptoms after a first COVID-19 event were asthenia (30.3%), followed by myalgia (13.7%), cough (12.4%), dyspnea (10.2%), concentration deficit (8.1%), headache (7.3%), and anosmia (6.5%), in decreasing order of prevalence. The risk of long COVID-19 at 30-60 days was significantly higher in HCWs hospitalized for COVID-19 (aOR = 3.34; 95%CI: 1.62; 6.89), those infected with SARS-CoV-2 during the early pandemic waves-namely the Wuhan (aOR = 2.16; 95%CI: 1.14; 4.09) or Alpha (aOR= 2.05; 95%CI: 1.25; 3.38) transmission periods-and progressively increasing with viral shedding time (VST), especially 15+ days (aOR = 3.20; 95%CI: 2.07; 4.94). Further determinants of long COVID-19 at 30-60 days since primary COVID-19 event were female sex (aOR = 1.91; 95%CI: 1.30; 2.80), age >40 years, abnormal BMI, or administrative services (reference category). In contrast, HCWs vaccinated with two doses before their primary infection (aOR = 0.57; 95%CI: 0.34; 0.94), undergraduate students, or postgraduate medical trainees were less likely to experience long COVID-19 at 30-60 days. Apart from pandemic waves, the main determinants of long COVID-19 at 30-60 days were confirmed at 61+ days. Conclusions: The risk of long COVID-19 following primary infection increased with the severity of acute disease and VST, especially during the initial pandemic waves, when more virulent viral strains were circulating, and susceptibility to SARS-CoV-2 was higher since most HCWs had not been infected yet, COVID-19 vaccines were still not available, and/or vaccination coverage was still building up. The risk of long COVID-19 therefore decreased inversely with humoral immunity at the individual level. Nevertheless, the prevalence of long COVID-19 was remarkably lower after SARS-CoV-2 reinfections regardless of vaccination status, suggesting that hybrid humoral immunity did not increase protection against the syndrome compared to immunity mounted by either natural infection or vaccination separately. Since the risk of long COVID-19 is currently low with Omicron and patients who developed the syndrome following SARS-CoV-2 infection in the early pandemic waves tend to return to a state of full health with time, a cost-effective approach to screen post-COVID-19 symptoms during the Omicron time could be restricted to vulnerable individuals developing severe disease and/or with prolonged VST.

Determinants of Anti-S Immune Response at 12 Months after SARS-CoV-2 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

BACKGROUND: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). METHODS: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 spike antibodies (IgG) in a cohort of 16,101 vaccinated HCW from eleven centers in Germany, Italy, Romania, Slovakia and Spain. Considering the skewness of the distribution, the serological levels were transformed using log or cubic standardization and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log or cubic antibody level and the corresponding 95% confidence interval (CI) for different factors and combined them in random-effects meta-analyses. RESULTS: We included 16,101 HCW in the analysis. A high antibody level was positively associated with age (RR = 1.04, 95% CI = 1.00-1.08 per 10-year increase), previous infection (RR = 1.78, 95% CI 1.29-2.45) and use of Spikevax [Moderna] with combinations compared to Comirnaty [BioNTech/Pfizer] (RR = 1.07, 95% CI 0.97-1.19) and was negatively associated with the time since last vaccine (RR = 0.94, 95% CI 0.91-0.98 per 30-day increase). CONCLUSIONS: These results provide insight about vaccine-induced immunity to SARS-CoV-2, an analysis of its determinants and quantification of the antibody decay trend with time since vaccination.

Multimorbidity and Serological Response to SARS-CoV-2 Nine Months after 1st Vaccine Dose: European Cohort of Healthcare Workers-Orchestra Project.

Understanding antibody persistence concerning multimorbidity is crucial for vaccination policies. Our goal is to assess the link between multimorbidity and serological response to SARS-CoV-2 nine months post-first vaccine. We analyzed Healthcare Workers (HCWs) from three cohorts from Italy, and one each from Germany, Romania, Slovakia, and Spain. Seven groups of chronic diseases were analyzed. We included 2941 HCWs (78.5% female, 73.4% ≥ 40 years old). Multimorbidity was present in 6.9% of HCWs. The prevalence of each chronic condition ranged between 1.9% (cancer) to 10.3% (allergies). Two regression models were fitted, one considering the chronic conditions groups and the other considering whether HCWs had diseases from ≥2 groups. Multimorbidity was present in 6.9% of HCWs, and higher 9-months post-vaccine anti-S levels were significantly associated with having received three doses of the vaccine (RR = 2.45, CI = 1.92-3.13) and with having a prior COVID-19 infection (RR = 2.30, CI = 2.15-2.46). Conversely, lower levels were associated with higher age (RR = 0.94, CI = 0.91-0.96), more time since the last vaccine dose (RR = 0.95, CI = 0.94-0.96), and multimorbidity (RR = 0.89, CI = 0.80-1.00). Hypertension is significantly associated with lower anti-S levels (RR = 0.87, CI = 0.80-0.95). The serological response to vaccines is more inadequate in individuals with multimorbidity.

Incidence and Determinants of Symptomatic and Asymptomatic SARS-CoV-2 Breakthrough Infections After Booster Dose in a Large European Multicentric Cohort of Health Workers-ORCHESTRA Project.

BACKGROUND: SARS-CoV-2 breakthrough infections (BI) after vaccine booster dose are a relevant public health issue. METHODS: Multicentric longitudinal cohort study within the ORCHESTRA project, involving 63,516 health workers (HW) from 14 European settings. The study investigated the cumulative incidence of SARS-CoV-2 BI after booster dose and its correlation with age, sex, job title, previous infection, and time since third dose. RESULTS: 13,093 (20.6%) BI were observed. The cumulative incidence of BI was higher in women and in HW aged < 50 years, but nearly halved after 60 years. Nurses experienced the highest BI incidence, and administrative staff experienced the lowest. The BI incidence was higher in immunosuppressed HW (28.6%) vs others (24.9%). When controlling for gender, age, job title and infection before booster, heterologous vaccination reduced BI incidence with respect to the BNT162b2 mRNA vaccine [Odds Ratio (OR) 0.69, 95% CI 0.63-0.76]. Previous infection protected against asymptomatic infection [Relative Risk Ratio (RRR) of recent infection vs no infection 0.53, 95% CI 0.23-1.20] and even more against symptomatic infections [RRR 0.11, 95% CI 0.05-0.25]. Symptomatic infections increased from 70.5% in HW receiving the booster dose since < 64 days to 86.2% when time elapsed was > 130 days. CONCLUSIONS: The risk of BI after booster is significantly reduced by previous infection, heterologous vaccination, and older ages. Immunosuppression is relevant for increased BI incidence. Time elapsed from booster affects BI severity, confirming the public health usefulness of booster. Further research should focus on BI trend after 4th dose and its relationship with time variables across the epidemics.

Corrigendum: Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: an individual-level analysis within 13 months in the ORCHESTRA cohort.

[This corrects the article DOI: 10.3389/fimmu.2022.1079884.].

Vasovagal Syncope at Work: A Narrative Review for an Occupational Management Proposal.

Syncope is a complex clinical manifestation that presents considerable diagnostic difficulties and, consequently, numerous critical issues regarding fitness for work, especially for high-risk tasks. To date, it is impossible to quantify the exact impact of syncope on work and public safety since it is highly improbable to identify loss of consciousness as the fundamental cause of work or driving-related accidents, especially fatal injuries. Working at high-risk jobs such as public transport operators, in high elevations, or with exposure to moving parts, construction equipment, fireworks, or explosives demand attention and total awareness. Currently, no validated criteria or indicators are available for occupational risk stratification of a patient with reflex syncope to return to work. By drawing inspiration from the updated literature, this narrative review intends to summarise the leading knowledge required regarding the return to work for subjects affected by syncope. According to the available data, the authors highlighted some key findings, summarised in macro-items, such as defined risk stratification for vasovagal accidents, return to work after a critical event, and a focus on pacemaker (PM) implementation. Lastly, the authors proposed a flowchart for occupational physicians to help them manage the cases of workers affected by syncope and exposed to levels of risk that could represent a danger to the workers' health.

Reduction of Excessive Dietary Sodium Consumption: Effectiveness of a Prevention Intervention among Health Workers in a Large Italian Hospital.

Excessive salt consumption is one of the leading causes of high blood pressure. Worldwide salt intake largely exceeds the WHO recommended amount. This study aimed to evaluate the prevalence of high salt consumers and the effectiveness of a short-term workplace educational intervention among health workers. An online survey, assessing daily salt consumption through the MINISAL-SIIA questionnaire, was sent to the 4911 health workers employed by the University Hospital of Verona, Italy. Health workers who had a high (total score ≥ 10) or moderate (total score = 8/9) salt consumption associated with obesity or arterial hypertension were invited to undergo a medical examination and a short individual counselling session. A total of 1665 health workers (34.0%) completed the online questionnaire; 40.9% and 12.6% had moderate and high salt intake, respectively. High salt intake was more prevalent in men, current and past smokers, and obese and overweight subjects. In 95 participants completing the clinical phase, median daily salt consumption decreased from 10 (p25-p75 8-11) to 7 g (6-8) (p < 0.001), systolic blood pressure from 130 (120-140) to 120 (120-130) mmHg and weight from 78 (62-87) to 75 (62-86) kg. More than half of health workers had an excessive salt intake. However, a brief educational intervention in the healthcare working setting can substantially reduce unhealthy dietary habits, fostering weight loss and blood pressure control. Studies with a longer follow-up are needed to evaluate the persistence over time of these effects.

SARS-CoV-2 Emergency Management in the ASL 1 Abruzzo Companies, Italy: An Autumn 2022 Cross-Sectional Investigation.

BACKGROUND: The SARS-CoV-2 pandemic still represents a public health emergency that affects workplaces and forces employers to develop technical, organizational and procedural measures safeguarding workers' health, particularly 'fragile' ones. This research aimed to assess employers' adherence to the emergency measures planned by the Italian government to hinder COVID-19 during Autumn 2022. METHODS: A cross-sectional study was conducted in Autumn 2022, with an 18-item questionnaire derived from the Italian State's governmental indications, sent by email to 51 companies of Marsica and Peligna Valley, L'Aquila, Southern Italy. RESULTS: A total of 20 recruited companies (65% were micro-enterprises, belonging to the food and financial sector) responded to the questionnaire within a mean time of 18 days (±11.64), which was lower for medium- and large-sized companies as well as for banking sector ones (p < 0.05). As regards intervention strategies, sanitization (92.7% of positive answers) and specific training (83.3%) showed almost full compliance in contrast to working organization (47.5%) and social distancing (61.7%). The companies that reported managing fragility (50%) belong almost exclusively to the banking sector, with predominantly office-based tasks. CONCLUSIONS: The study provided insight into critical issues relating to compliance with national legislative directives and the crucial role of occupational physicians as global advisors for all workplaces.

Determinants of Anti-S Immune Response at 9 Months after COVID-19 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

Background: The persistence of antibody levels after COVID-19 vaccination has public health relevance. We analyzed the determinants of quantitative serology at 9 months after vaccination in a multicenter cohort. Methods: We analyzed data on anti-SARS-CoV-2 spike antibody levels at 9 months from the first dose of vaccinated HCW from eight centers in Italy, Germany, Spain, Romania and Slovakia. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log antibody level and the corresponding 95% confidence interval (CI), and combined them in random-effects meta-analyses. Finally, we conducted a trend analysis of 1 to 7 months' serology within one cohort. Results: We included 20,216 HCW with up to two vaccine doses and showed that high antibody levels were associated with female sex (p = 0.01), age (RR = 0.87, 95% CI = 0.86-0.88 per 10-year increase), 10-day increase in time since last vaccine (RR = 0.97, 95% CI 0.97-0.98), previous infection (3.03, 95% CI = 2.92-3.13), two vaccine doses (RR = 1.22, 95% CI = 1.09-1.36), use of Spikevax (OR = 1.51, 95% CI = 1.39-1.64), Vaxzevria (OR = 0.57, 95% CI = 0.44-0.73) or heterologous vaccination (OR = 1.33, 95% CI = 1.12-1.57), compared to Comirnaty. The trend in the Bologna cohort, based on 3979 measurements, showed a decrease in mean standardized antibody level from 8.17 to 7.06 (1-7 months, p for trend 0.005). Conclusions: Our findings corroborate current knowledge on the determinants of COVID-19 vaccine-induced immunity and declining trend with time.

SARS-CoV-2 and Its Variants in Thrice-Infected Health Workers: A Case Series from an Italian University Hospital.

BACKGROUND: We described a SARS-CoV-2 thrice-infected case series in health workers (HW) to evaluate patient and virus variants and lineages and collect information on variables associated with multiple infections. METHODS: A retrospective analysis of clinical and laboratory characteristics of SARS-CoV-2 thrice-infected individuals was carried out in Verona University Hospital, concurrent with the ORCHESTRA project. Variant analysis was conducted on a subset of available specimens. RESULTS: Twelve HW out of 7368 were thrice infected (0.16%). Symptomatic infections were reported in 63.6%, 54.5% and 72.7% of the first, second and third infections, respectively. Nine subjects were fully vaccinated at the time of the third infection, and five had an additional booster dose. The mean time to second infection was 349.6 days (95% CI, 138-443); the mean interval between the second and third infection was 223.5 days (95% CI, 108-530) (p = 0.032). In three cases, the second and third infections were caused by the Omicron variant, but different lineages were detected when the second vs third infections were sequenced. CONCLUSIONS: This case series confirms evidence of multiple reinfections with SARS-CoV-2, even from the same variant, in vaccinated HW. These results reinforce the need for continued infection-specific prevention measures in previously infected and reinfected HW.

Determinants of anti-S immune response at 6 months after COVID-19 vaccination in a multicentric European cohort of healthcare workers - ORCHESTRA project.

Background: The duration of immune response to COVID-19 vaccination is of major interest. Our aim was to analyze the determinants of anti-SARS-CoV-2 IgG titer at 6 months after 2-dose vaccination in an international cohort of vaccinated healthcare workers (HCWs). Methods: We analyzed data on levels of anti-SARS-CoV-2 Spike antibodies and sociodemographic and clinical characteristics of 6,327 vaccinated HCWs from 8 centers from Germany, Italy, Romania and Slovakia. Time between 1st dose and serology ranged 150-210 days. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors, obtaining standardized values. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of 1 standard deviation of log antibody level and corresponding 95% confidence interval (CI), and finally combined them in random-effects meta-analyses. Results: A 6-month serological response was detected in 99.6% of HCWs. Female sex (RR 1.10, 95%CI 1.00-1.21), past infection (RR 2.26, 95%CI 1.73-2.95) and two vaccine doses (RR 1.50, 95%CI 1.22-1.84) predicted higher IgG titer, contrary to interval since last dose (RR for 10-day increase 0.94, 95%CI 0.91-0.97) and age (RR for 10-year increase 0.87, 95%CI 0.83-0.92). M-RNA-based vaccines (p<0.001) and heterologous vaccination (RR 2.46, 95%CI 1.87-3.24, one cohort) were associated with increased antibody levels. Conclusions: Female gender, young age, past infection, two vaccine doses, and m-RNA and heterologous vaccination predicted higher antibody level at 6 months. These results corroborate previous findings and offer valuable data for comparison with trends observed with longer follow-ups.

Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers.

Introduction: The anti-spike (S) IgG assay is the most widely used method to assess the immunological response to COVID-19 vaccination. Several studies showed that subjects with perivaccination infection have higher anti-S IgG titers. However, a cut-off has not yet been identified so far for distinguishing infected subjects after vaccination. This study thus evaluates the performance of the anti-S IgG assay in identifying subjects with breakthrough infections (BIs) and its potential usefulness for screening healthcare workers (HCWs). Methods: Out of 6400 HCWs of the University Hospital of Verona vaccinated with two doses of BNT162b2, 4462 never infected before subjects who had completed primary vaccination were tested for IgG anti-S 6 to 9 months after the second dose. Of these, 59 (1.3%) had a BI. The discriminant power of IgG anti-S in detecting previous breakthrough infection was tested by constructing receiver operating characteristic (ROC) curves. Results: The discriminant power for BI was rather good (area under the curve (AUC), 0.78) and increased with decreasing time elapsed between antibody titer assessment and previous SARS-CoV-2 infection. Accuracy (AUC) sensitivity increased from 0.78 (95% CI 0.70−0.85) for BI in the previous six months to 0.83 (95% CI 0.67−0.99) for those in the previous two months, and from 0.68 to 0.80, respectively. The specificity (0.86) and optimal cut-off (935 BAU/mL) remained unchanged. However, BI were rather rare (1.3%), so the positive predictive value (PPV) was low. Only 40 of the 664 HCWs with antibody titer > 935 BAU/mL had previously confirmed BI, yielding a PPV of only 6.0%. When adopting as cut-off the 90th percentile (1180 BAU/mL), PPV increased to 7.9% (35/441). Conclusions: The anti-S IgG assay displayed good sensitivity and specificity in discriminating subjects with BI, especially in recent periods. However, BIs were rare among HCWs, so that the anti-S IgG assay may have low PPV in this setting, thus limiting the usefulness of this test as a screening tool for HCWs. Further studies are needed to identify more effective markers of a previous infection in vaccinated subjects.

Smoking Habits and Workplace Health Promotion among University Students in Southern Italy: A Cross-Sectional Pilot Investigation.

The study aimed to investigate the tobacco smoking prevalence, habits and awareness among a cohort of healthcare students from a university hospital in southern Italy and the associations with socio-demographic determinants. A secondary outcome was to estimate the educational needs to receive information on smoking-related risk factors. Five hundred and forty-nine students completed a self-administered questionnaire (180 male and 369 female, average age 25 yo, ±5.9 SD), enrolled from October 2018 to November 2019 at the University of Naples 'Luigi Vanvitelli', and the collected data were analysed by descriptive and inferential statistical analysis. The sample's prevalence of current smokers was 25.3%, without a significant sex difference. The multiple logistic regression model showed the link between smoking habits and alcoholic beverage consumption (p < 0.001) and living with smokers (p = 0.003). The enrolled cohort does not seem to need more information about the risks of cigarette smoking (p = 0.028). The data analysis and the comparison with the current literature allowed the authors to hypothesise a training model to be adopted within a workplace health promotion programme managed by an occupational physician. This model included targeted training for smoking dissuasion, focusing on sex and gender, cohabitant's influence, and combined addiction management. Further research will focus on the effectiveness of these proposed models.

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers.

BACKGROUND: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. METHODS: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). RESULTS: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). CONCLUSION: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated.

Serological response after SARS-CoV2 vaccination in healthcare workers: a multicenter study.

INTRODUCTION: Characterizing immunological response following COVID-19 vaccination is an important public health issue. The objectives of the present analysis were to investigate the proportion, level and the determinants of humoral response from 21 days to three months after the first dose in vaccinated healthcare workers (HCWs). METHODS: We abstracted data on level of anti-SARS-CoV-2 Spike antibodies (IgG) and sociodemographic characteristics of 17,257 HCWs from public hospitals and public health authorities from three centers in Northern Italy who underwent COVID-19 vaccination (average 70.6 days after first dose). We fitted center-specific multivariate regression models and combined them using random-effects meta-analyses. RESULTS: A humoral response was elicited in 99.3% of vaccinated HCW. Female sex, young age, and previous COVID-19 infection were predictors of post-vaccination antibody level, and a positive association was also detected with pre-vaccination serology level and with time between pre- and post-vaccination testing, while a decline of antibody level was suggested with time since vaccination. CONCLUSIONS: These results stress the importance of analyzing retrospective data collected via occupational health surveillance of HCWs during the COVID-19 epidemic and following vaccination. They need to be confirmed in larger series based on prospectively collected data.

Returning to Work after the COVID-19 Pandemic Earthquake: A Systematic Review.

BACKGROUND: The ongoing SARS-CoV-2 pandemic has disrupted life and work habits and has produced landmark changes worldwide. This systematic review aimed to analyse the management of Return to Work (RTW) by work organisations following the virus spread. METHODS: A selection of 2477 papers, using string research on PubMed, Embase, Web of Science and Scopus from January 2020 to October 2021, were analysed. RESULTS: Fifty-one articles were finally included, and the results obtained were discussed from three different points of view. Twenty articles concerning 'Remodelling of Work Organization' proposed some model strategies for resumption to work. Twenty-one papers, including 'Clinical Evaluation of Workers', mostly explored the psychosocial impact of returned workers. Finally, twelve articles explored the best 'Testing Strategies related to RTW'. Despite the heterogeneity of included articles, several interesting approaches have emerged in managing RTW. CONCLUSIONS: The reported experiences could help to develop an RTW model for COVID-19 and future pandemics.