Peptidomic and proteomic analysis of stool for diagnosing IBD and deciphering disease pathogenesis.

Background The sensitivities and specificities of C-reactive protein (CRP) and faecal calprotectin (fCal), as recommended for inflammatory bowel diseases (IBD) diagnosis and monitoring, are low. Our aim was to discover new stool protein/peptide biomarkers for diagnosing IBD. Methods For peptides, MALDI-TOF/MS (m/z 1000-4000) was performed using stools from an exploratory (34 controls; 72 Crohn's disease [CD], 56 ulcerative colitis [UC]) and a validation (28 controls, 27 CD, 15 UC) cohort. For proteins, LTQ-Orbitrap XL MS analysis (6 controls, 5 CD, 5 UC) was performed. Results MALDI-TOF/MS spectra of IBD patients had numerous features, unlike controls. Overall, 426 features (67 control-associated, 359 IBD-associated) were identified. Spectra were classified as control or IBD (absence or presence of IBD-associated features). In the exploratory cohort, the sensitivity and specificity of this classification algorithm were 81% and 97%, respectively. Blind analysis of the validation cohort confirmed 97% specificity, with a lower sensitivity (55%) paralleling active disease frequency. Following binary logistic regression analysis, IBD was independently correlated with MALDI-TOF/MS spectra (p < 0.0001), outperforming fCal measurements (p = 0.029). The IBD-correlated m/z 1810.8 feature was a fragment of APC2, homologous with APC, over-expressed by infiltrating cells lining the surface in UC or the muscularis-mucosae in CD (assessed by immunohistochemistry). IBD-associated over-expressed proteins included immunoglobulins and neutrophil proteins, while those under-expressed comprised proteins of the nucleic acid assembly or those (OLFM4, ENPP7) related to cancer risk. Conclusions Our study provides evidence for the clinical utility of a novel proteomic method for diagnosing IBD and insight on the pathogenic role of APC. Moreover, the newly described IBD-associated proteins might become tools for cancer risk assessment in IBD patients.

The importance of sex as a risk factor for hospital readmissions due to pulmonary diseases.

BACKGROUND: Pulmonary diseases are a common and costly cause of 30-day readmissions. Few studies have focused on the difference in risk for rehospitalization between men and women in older patients. In this study we analyzed the association between sex and the risk of readmission in a cohort of patients admitted to the hospital for chronic obstructive pulmonary disease (COPD) exacerbation and other major pulmonary diseases. METHODS: This was a retrospective cohort study based on administrative data collected in the Veneto Region in 2016. We included 14,869 hospital admissions among residents aged ≥65 years for diagnosis related groups (DRGs) of the most common disorders of the respiratory system: bronchitis and asthma, pneumonia, pulmonary edema, respiratory failure, and COPD. Multilevel logistic regressions were performed to test the association between 30-day hospital readmission and sex, adjusting for confounding factors. RESULTS: For bronchitis and asthma, male patients had significantly higher odds of 30-day readmission than female patients (adjusted odds ratio (aOR), 2.07; 95% confidence interval (CI), 1.11-3.87). The odds of readmission for men were also significantly higher for pneumonia (aOR, 1.40; 95% CI, 1.13-1.72), for pulmonary edema and respiratory failure (aOR, 1.28; 95% CI, 1.05-1.55), and for COPD (aOR, 1.34; 95% CI, 1.00-1.81). CONCLUSIONS: This study found that male sex is a major risk factors for readmission in patients aged more than 65 years with a primary pulmonary diagnosis. More studies are needed to understand the underlying determinants of this phenomena and to provide targets for future interventions.

Education level and hospitalization for ambulatory care sensitive conditions: an education approach is required.

BACKGROUND: Studies in several different countries and settings suggest that ambulatory care-sensitive conditions (ACSCs)-related hospitalizations could be associated more with socioeconomic variables than with the quality of primary healthcare services. The aim of the present study was to analyze the potential links between education levels or other social determinants and ACSC-related hospitalization rates. METHODS: We analyzed a total of 467 504 records of ordinary discharges after acute hospitalization in 2015-16 for patients 20-74 years old residing in the Veneto Region. We calculated the prevention quality indicators (PQIs) developed by the Agency for Healthcare Research and Quality. Rate ratios (RRs) and 95% confidence intervals (95% CIs) were estimated with a set of Poisson regressions to measure the relative risk by sociodemographic level. RESULTS: Hospitalizations for ACSCs accounted for 3.9% of all hospital admissions (18 436 discharges), and the crude hospitalization rate for ACSCs among 20- to 74-year-olds was 26.6 per 10 000 inhabitants (95% CI, 25.8-27.4). For all conditions, we found a significant association with formal education. In the case of the overall composite PQI#90, e.g. poorly educated people (primary school or no schooling) were at significantly higher risk of hospitalization for ACSCs than the better educated (RR, 4.50; 95% CI, 4.13-4.91). CONCLUSIONS: Currently available administrative data regarding ACSCs may be used effectively for reveal equity issues in the provision of health care. Our results indicate that an educational approach inside Primary Health Care could address the extra risk for preventable healthcare demands associated with poorly educated patients.

Improving IBD diagnosis and monitoring by understanding preanalytical, analytical and biological fecal calprotectin variability.

BACKGROUND: The appropriate clinical use of fecal calprotectin (fCal) might be compromised by incomplete harmonization between assays and within- and between-subjects variability. Our aim was to investigate the analytical and biological variability of fCal in order to provide tools for interpreting fCal in the clinical setting. METHODS: Experiments were conducted to investigate the effects of temperature and storage time on fCal. Thirty-nine controls were enrolled to verify biological variability, and a case-control study was conducted on 134 controls and 110 IBD patients to compare the clinical effectiveness of three different fCal assays: ELISA, CLIA and turbidimetry. RESULTS: A 12% decline in fCal levels was observed within 24 h following stool collection irrespective of storage temperature. Samples were unstable following a longer storage time interval at room temperature. Within- and between-subjects fCal biological variability, at 31% and 72% respectively, resulted in a reference change value (RCV) in the region of 100%. fCal sensitivity in distinguishing between controls and IBD patients is satisfactory (68%), and the specificity high (93%) among young (<65 years), but not among older (≥65 years) subjects (ROC area: 0.584; 95% CI: 0.399-0.769). Among the young, assays have different optimal thresholds (120 µg/g for ELISA, 50 µg/g for CLIA and 100 µg/g for turbidimetry). CONCLUSIONS: We recommend a standardized preanalytical protocol for fCal, avoiding storage at room temperature for more than 24 h. Different cutoffs are recommended for different fCal assays. In monitoring, the difference between two consecutive measurements appears clinically significant when higher than 100%, the fCal biological variability-derived RCV.

[Relevance and role of guideline values for chemical risk assessment.] / Significato e ruolo dei valori guida nella valutazione del rischio chimico.

OBJECTIVES: Guideline values have been defined by the ad hoc S.I.M.L.I.I. Working Group as "the level of a risk factor, previously established for an environmental or biological context, to which the levels actually measured for/in the workers should be compared, in order to assess their degree of exposure". METHODS: Guideline values include limit values, action levels and reference values, and may refer to an environmental or biological matrix. RESULTS: The present paper aims to discuss the methodologies currently used for the definition of the most relevant guideline and limit values at the national and international level, with a particular attention to those used in the European Union (OEL). CONCLUSIONS: It is concluded that a correct use of guideline values represents a fundamental tool for both the assessment and the management of chemical risk in workers exposed to toxic and/or carcinogenic substances.

[Health and work in a gender perspective.] / Salute e lavoro in un'ottica di genere.

OBJECTIVES: A literature review was performed to highlight which work-related diseases express sex/gender differences in health outcomes and focus the main limits of studies in this field. METHODS: The research, carried out on PubMed by specific search string, identified 4828 articles (1997-2017 period) of which 381 are eligible for review (4-22%, depending on the disease). RESULTS: Among them, 68% reported sex/gender differences in health outcomes, which in most cases appear to be due to different exposure and/or work segregation rather than to biological differences. However, few studies place this assessment among the research goals and results are almost never discussed and hypothesis are seldom formulated about any observed differences. CONCLUSIONS: It seems necessary to use research methodologies and study design that can detect and explain the described complexity and useful in defining appropriate preventive strategies.

[Gender-sensitive risk assessment and health medical surveillance: some operative tools.] / Valutazione dei rischi e sorveglianza sanitaria in ottica di genere: proposta di strumenti operativi.

OBJECTIVES: A thorough and fully application of the principles of gender mainstreaming, in accordance with the European Community guidelines, to the health and safety at work, implies the systematic review of the whole prevention from the gendered point of view. This means that both biology- and gender-based differences between male and female workers should be conceived not only as determinants of health but also as factors affecting either positively or negatively the health and safety risk prevention. In this evolutionary cultural step the role of the occupational physician is particularly important. METHODS: In this paper we propose some operative tools that can concretely implement gender perspective in all the various areas of prevention, where the occupational physician has a leading, if not even exclusive, role such as risk assessment, training and health medical surveillance.

Sinonasal cancer in a worker exposed to chromium in an unusual industrial sector.

BACKGROUND: Occupational exposure to chromium is carcinogenic for human respiratory system. Due to the low incidence of sinonasal malignancies, there is still a paucity of evidence to confirm that chromium(VI) exposure is a cause of nasal cancer. OBJECTIVES: To report on a sinonasal cancer (SNC) of rare occupational origin, increasing the awareness on epidemiological knowledge of occupational exposures to chromium compounds. METHODS: We describe a case of a 64-year-old chrome plater who worked in the galvanic industry in the early 1970s. After a latency period of 39 years, he was diagnosed with sinonasal undifferentiated carcinoma (SNUC). A brief review of the literature was conducted. RESULTS: A thorough occupational history revealed a 4-year-long occupational exposure to chromium(VI) during a magnesium cylinder plating process involved in computer production. The patient underwent endoscopic endonasal removal of the SNUC. He is alive with no evidence of disease at 40-month follow-up. Our literature review identified 8 papers concerning 40 cases of chrome-induced sinonasal tumors. The maximum relative risk of SNC developing in chromium-exposed workers was 15.4. CONCLUSIONS: When dealing with patients diagnosed with SNC, the possibility of an underlying occupational risk is worth further investigation. Because chromium exposure is rare, and the incidence of SNUC is low, any information emerging on clinical and exposure-related aspects of SNCs in chrome plating workers can contribute to adding evidence on the possible causal relationship between chromium and sinonasal malignancies.

Methodology to define biological reference values in the environmental and occupational fields: the contribution of the Italian Society for Reference Values (SIVR).

BACKGROUND: Biological reference values (RVs) explore the relationships between humans and their environment and habits. RVs are fundamental in the environmental field for assessing illnesses possibly associated with environmental pollution, and also in the occupational field, especially in the absence of established biological or environmental limits. OBJECTIVES: The Italian Society for Reference Values (SIVR) determined to test criteria and procedures for the definition of RVs to be used in the environmental and occupational fields. METHODS: The paper describes the SIVR methodology for defining RVs of xenobiotics and their metabolites. Aspects regarding the choice of population sample, the quality of analytical data, statistical analysis and control of variability factors are considered. The simultaneous interlaboratory circuits involved can be expected to increasingly improve the quality of the analytical data. RESULTS: Examples of RVs produced by SIVR are presented. In particular, levels of chromium, mercury, ethylenethiourea, 3,5,6-trichloro-2-pyridinol, 2,5-hexanedione, 1-hydroxypyrene and t,t-muconic acid measured in urine and expressed in micrograms/g creatinine (µg/g creat) or micrograms/L (µg/L) are reported. CONCLUSIONS: With the proposed procedure, SIVR intends to make its activities known to the scientific community in order to increase the number of laboratories involved in the definition of RVs for the Italian population. More research is needed to obtain further RVs in different biological matrices, such as hair, nails and exhaled breath. It is also necessary to update and improve the present reference values and broaden the portfolio of chemicals for which RVs are available. In the near future, SIVR intends to expand its scientific activity by using a multivariate approach for xenobiotics that may have a common origin, and to define RVs separately for children who may be exposed more than adults and be more vulnerable.

Assessment of exposure to oak wood dust using gallic acid as a chemical marker.

OBJECTIVES: The American Conference of Governmental Industrial Hygienists (ACGIH) has classified oak dust as a human carcinogen (A1), based on increased sinus and nasal cancer rates among exposed workers. The aims of this study were to investigate the use of gallic acid (GA) as a chemical marker of occupational exposure to oak dusts, to develop a high-performance liquid chromatography-diode array detector method to quantify GA and to apply the method in the analysis of oak dust samples collected in several factories. METHODS: A high-performance liquid chromatography method was developed to detect GA in oak wood dust. The method was tested in the field, and GA was extracted from inhalable oak wood dust collected using the Institute of Occupational Medicine inhalable dust sampler in the air of five woodworking plants where only oak wood is used. RESULTS: A total of 57 samples with dust concentrations in the range of 0.27-11.14 mg/m(3) were collected. Five of these samples exceeded the Italian threshold limit value of 5 mg/m(3), and 30 samples exceeded the ACGIH TLV of 1 mg/m(3). The GA concentrations were in the range 0.02-4.18 µg/m(3). The total oak dust sampled was correlated with the GA content with a correlation coefficient (r) of 0.95. CONCLUSIONS: The GA in the tannic extracts of oak wood may be considered a good marker for this type of wood, and its concentration in wood dust sampled in the work environment is useful in assessing the true exposure to carcinogenic oak dust.

Woodworkers and the inflammatory effects of softwood/hardwood dust: evidence from nasal cytology.

Our primary aim was to use nasal cytology to compare a group of woodworkers with a group of unexposed subjects to see whether wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary aim was to seek any differences in nasal symptoms or nasal cytology between workers exposed to softwood vs hardwood dust, thereby comparing the inflammatory harmful potential of the two woods. Among 117 woodworkers at factories in the Veneto region (Italy), 40 exposed to either softwood or hardwood dust were assessed by means of a questionnaire, nasal cytology, and personal wood dust sampling, and compared with 40 unexposed controls. Woodworkers reported significantly more nasal symptoms than controls (p = 0.0007). The woodworker group's nasal smears contained significantly more neutrophils (p < 0.00001) and lymphocytes (p = 0.02) than the control group's. The softwood workers had significantly lower levels of personal exposure to wood dust than the hardwood workers (p = 0.04); there were no significant differences in age, history of cigarette smoking, or period of exposure between these two sub-cohorts of woodworkers. A statistical trend indicated that softwood workers had more eosinophils (p = 0.05) and lymphocytes (p = 0.05) in their rhinocytograms. Nasal cytology revealed chronic inflammatory rhinitis in a significant proportion of woodworkers' enroled in this study. It also suggested a different harmful potential for softwood and hardwood dust. Nasal cytology could prove useful in screening woodworkers for chronic inflammatory rhinitis. Further investigations are needed to examine the role of different types of wood dust in nasal inflammation.

High-frequency hearing thresholds: effects of age, occupational ultrasound and noise exposure.

PURPOSE: It has been suggested that high-frequency audiometry (HFA) could represent a useful preventive measure in exposed workers. The aim was to investigate the effects of age, ultrasound and noise on high-frequency hearing thresholds. METHODS: We tested 24 industrial ultrasound-exposed subjects, 113 industrial noise-exposed subjects and 148 non-exposed subjects. Each subject was tested with both conventional-frequency (0.125-8 kHz) and high-frequency (9-18 kHz) audiometry. RESULTS: The hearing threshold at high frequency deteriorated as a function of age, especially in subjects more than 30 years old. The ultrasound-exposed subjects had significantly higher hearing thresholds than the non-exposed ones at the high frequencies, being greatest from 10 to 14 kHz. This hearing loss was already significantly evident in subjects with exposure <5 years and increased with years of exposure and advancing age. The noise exposure group had significantly higher hearing thresholds than the non-exposed group at the conventional frequencies 4 and 6 kHz and at the high frequency of 14 kHz. After stratification for age, there was a significant difference between the two groups at 9-10 and 14-15 kHz only for those under 30 years of age. CONCLUSION: Multivariate analysis indicated that age was the primary predictor, and noise and ultrasound exposure the secondary predictors of hearing thresholds in the high-frequency range. The results suggest that HFA could be useful in the early diagnosis of noise-induced hearing loss in younger groups of workers (under 30 years of age).

Long term follow-up of heart rate variability in healthcare workers with mild COVID-19.

Introduction: Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available. Methods: In this study, we conducted a comprehensive clinical and functional follow-up on healthcare workers (HCWs) with former mild COVID-19 (group 1, n = 67), to delineate the trajectory of post-acute autonomic imbalance, we previously detected in a case-control study. Additionally, we assessed HCWs for which a test before SARS-CoV-2 infection was available (group 2, n = 29), who later contracted SARS-CoV-2, aiming to validate findings from our prior case-control investigation. We evaluated autonomic nervous system heart modulation by means of time and frequency domain heart rate variability analysis (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings, were obtained at about 6, 13 months and both at 6 and 13 months from the negative SARS-CoV-2 naso-pharyngeal swab (NPS) for group 1 and at about 1-month from the negative NPS for group 2. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Results: Group 1 was split into three subgroups clinically and functionally followed at, about 6 months (subgroup-A, n = 17), 13 months (subgroup-B, n = 37) and both at 6 and 13 months (subgroup-C, n = 13) from the negative SARS-CoV-2 NPS. In subgroup-A, at 6-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed an increase in normalized high frequency power (nHF) (t = 2.99, p = 0.009), a decrease in the normalized low frequency power (nLF) (t = 2.98, p = 0.009) and in the LF/HF ratio (t = 3.13, p = 0.006). In subgroup B, the comparison of the spectral components in the frequency domain HRV parameters, at 13-month follow-up compared with baseline, showed an increase in nHF (t = 2.54, p = 0.02); a decrease in nLF (t = 2.62, p = 0.01) and in the LF/HF ratio (t = 4.00, p = 0.0003). In subgroup-C, at both 6 and 13-month follow-ups, the spectral components in the frequency domain HRV parameters were higher than baseline in nHF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively); lower in nLF (t = 2.64, p = 0.02 and (t = 2.13, p = 0.05, respectively), and in LF/HF (t = 1.92, p = 0.08 and (t = 2.43, p = 0.03, respectively). A significant proportion of HCWs reported persistent COVID-19 symptoms at both the 6 and 13-month follow-ups, seemingly unrelated to cardiac autonomic balance. In group 2 HCWs, at 1-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed a decrease in nHF (t = 2.19, p = 0.04); an increase in nLF (t = 2.15, p = 0.04) and in LF/HF (t = 3.49, p = 0.002). Conclusion: These results are consistent with epidemiological data suggesting a higher risk of acute cardiovascular complications during the first 30 days after COVID-19. The SARS-CoV-2 associated autonomic imbalance in the post-acute phase after recovery of mild COVID-19 resolved 6 months after the first negative SARS-CoV-2 NPS. However, a significant proportion of HCWs reported long-term COVID-19 symptoms, which dot not seems to be related to cardiac autonomic balance. Future research should certainly further test whether autonomic imbalance has a role in the mechanisms of long-COVID syndrome.

[Considerations on the limit values for benzene]. / Considerazioni sui valori limite per il benzene.

Occupational exposure limits and guideline values for the general population proposed for benzene by several international bodies are discussed and compared with the Italian and EU occupational limit values, taking also into account the criteria used for their derivation. Benzene is an environmental pollutant, and the EU guideline value for ambient air is 5 microg/m3, based on carcinogenic risk. Presently, occupational exposures are greatly reduced, and in many instances close to those of the general population. Consequently, it does not seem to be appropriate to maintain the Italian and the EU occupational exposure limits of 1 ppm (3.2 mg/m3), which are inconsistent with the ALARA principle and not justified by technological constraints. It should be pointed out that, in any case, preventive interventions should be carried out, beyond the compliance with the established limit values, in order to ensure the lowest exposure and by carrying out biological monitoring as a tool to verify the appropriateness of risk management measures.

Persistent Increase of Sympathetic Activity in Post-Acute COVID-19 of Paucisymptomatic Healthcare Workers.

Healthcare workers (HCWs) represent a population with a significant burden of paucisymptomatic COVID-19, as the general population. We evaluated autonomic nervous system activity by means of heart rate variability (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings were obtained 30 days (IQR 5.25-55.75) after a negative naso-pharyngeal swab for SARS-CoV-2 in 44 cases and compared with ECGs of 44 controls with similar age and sex distribution. Time and frequency domain HRV were evaluated. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded. Frequency domain HRV analysis showed a significantly higher low/high-frequency power ratio (LF/HF) in the case study compared with controls (t = 2.84, p = 0.006). In time domain HRV analysis, mean standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were significantly lower for cases compared with controls (t = -2.64, p = 0.01 and t = -3.27, p = 0.002, respectively). In the post-acute phase of infection, SARS-CoV-2 produces an autonomic imbalance mirrored by a reduction in HRV. These results are consistent with epidemiological data that suggest a higher risk of acute cardiovascular complications in the first 30 days after COVID-19 infection.

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.

The impact of SARS-CoV-2 on healthcare workers of a large University Hospital in the Veneto Region: risk of infection and clinical presentation in relation to different pandemic phases and some relevant determinants.

Aim: The aim of this study is to evaluate the incidence of SARS-CoV-2 infection and the prevalence of COVID-19-related symptoms in relation to pandemic phases and some relevant variables in a cohort of 8,029 HCWs from one of the largest Italian University Hospitals. Methods: A single-center retrospective study was performed on data collected during SARS-CoV-2 infection surveillance of HCWs. Cox's multiple regression was performed to estimate hazard ratios of SARS-CoV-2 infection. Logistic multivariate regression was used to assess the risk of asymptomatic infections and the onset of the most frequent symptoms. All analyses were adjusted for sociodemographic and occupational factors, pandemic phases, vaccination status, and previous infections. Results: A total of 3,760 HCWs resulted positive (2.0%-18.6% across five study phases). The total incidence rate of SARS-CoV-2 infection was 7.31 cases per 10,000 person-days, significantly lower in phase 1 and higher in phases 4 and 5, compared to phase 3. Younger HCWs, healthcare personnel, and unvaccinated subjects showed a higher risk of infection. Overall, 24.5% were asymptomatic infections, with a higher probability for men, physicians, and HCWs tested for screening, fully vaccinated, and those with previous infection. The clinical presentation changed over the phases in relation to vaccination status and the emergence of new variants. Conclusion: The screening activities of HCWs allowed for the early detection of asymptomatic cases, limiting the epidemic clusters inside the hospital wards. SARS-CoV-2 vaccination reduced infections and symptomatic cases, demonstrating again its paramount value as a preventive tool for occupational and public health.

Comparison of Adverse Effects of Two SARS-CoV-2 Vaccines Administered in Workers of the University of Padova.

Introduction: In Italy, on December 2020, workers in the education sector were identified as a priority population to be vaccinated against COVID-19. The first authorised vaccines were the Pfizer-BioNTech mRNA (BNT162b2) and the Oxford-AstraZeneca adenovirus vectored (ChAdOx1 nCoV-19) vaccines. Aim: To investigate the adverse effects of two SARS-CoV-2 vaccines in a real-life preventive setting at the University of Padova. Methods: Vaccination was offered to 10116 people. Vaccinated workers were asked to voluntarily report symptoms via online questionnaires sent to them 3 weeks after the first and the second shot. Results: 7482 subjects adhered to the vaccination campaign and 6681 subjects were vaccinated with ChAdOx1 nCoV-19 vaccine and 137 (fragile subjects) with the BNT162b2 vaccine. The response rate for both questionnaires was high (i.e., >75%). After the first shot, the ChAdOx1 nCoV-19 vaccine caused more fatigue (p < 0.001), headache (p < 0.001), myalgia (p < 0.001), tingles (p = 0.046), fever (p < 0.001), chills (p < 0.001), and insomnia (p = 0.016) than the BNT162b2 vaccine. After the second dose of the BNT162b2 vaccine, more myalgia (p = 0.033), tingles (p = 0.022), and shivers (p < 0.001) than the ChAdOx1 nCoV-19 vaccine were elicited. The side effects were nearly always transient. Severe adverse effects were rare and mostly reported after the first dose of the ChAdOx1 nCoV-19 vaccine. They were dyspnoea (2.3%), blurred vision (2.1%), urticaria (1.3%), and angioedema (0.4%). Conclusions: The adverse effects of both vaccines were transient and, overall, mild in severity.

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.