Revealing the Hidden Impacts: Insights into Biological Aging and Long-Term Effects in Pauci- and Asymptomatic COVID-19 Healthcare Workers.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers-DNA methylation age (DNAmAge) and telomere length (TL)-in blood leukocytes, nasal cells (NCs), and induced sputum (IS) one year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data from questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male sex, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p < 0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p < 0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p ≤ 0.05) and NCs (p < 0.001) and were biologically older than COPD patients (p < 0.05). These findings suggest the need to monitor aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Colorectal cancer and inflammatory bowel diseases share common salivary proteomic pathways.

Inflammatory bowels diseases (IBD) are high risk conditions for colorectal cancer (CRC). The discovery of IBD and CRC noninvasive protein/peptide biomarkers using saliva and feces was the aim of this study involving 20 controls, 25 IBD (12 Crohn's Disease-CD), 37 CRC. By untargeted proteomic (LTQ-Orbitrap/MS), a total of 152 proteins were identified in saliva. Absent in controls, 73 proteins were present in both IBD and CRC, being mainly related to cell-adhesion, cadherin-binding and enzyme activity regulation (g-Profiler). Among the remaining 79 proteins, 14 were highly expressed in CD and 11 in CRC. These proteins clustered in DNA replication/expression and innate/adaptive immunity. In stool, endogenous peptides from 30 different proteins were identified, two being salivary and CD-associated: Basic Proline-rich Protein 1 (PRBs) and Acidic Proline-rich Phosphoprotein. Biological effects of the PRBs-related peptides GQ-15 and GG-17 found in CD stool were evaluated using CRC cell lines. These peptides induced cell proliferation and activated Erk1/2, Akt and p38 pathways. In conclusion, the salivary proteome unveiled DNA stability and immunity clusters shared between IBD and CRC. Salivary PRB-derived peptides, enriched in CD stool, stimulate CRC cell proliferation and the pro-oncogenic RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways suggesting a potential involvement of PRBs in IBD and cancer pathogenesis.

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.

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.

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.

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.

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.

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.

Response to Vaccination against Mumps in Medical Students: Two Doses Are Needed.

Mumps is a vaccine-preventable infectious disease diffuse worldwide. The implementation of mumps vaccination reduced largely the spread of infection. On 11,327 Medical School students the prevalence of mumps positive antibodies was evaluated according to dose/doses of vaccine, year of birth and sex. Compliance to mumps vaccine was low in students born before 1990 but increased consistently after this year, above all compliance to two doses, due to the implementation of the vaccine offer. Positivity of mumps antibodies is significantly (p < 0.0001) lower in students vaccinated once (71.2%) compared to those vaccinated twice (85.4%). In addition, students born after 1995, largely vaccinated twice, showed a seropositivity near to 90%. Further, females had a significantly (p < 0.0001) higher proportion of positive antibodies after vaccination than males, both one (74.6% vs. 64.7%) and two doses (86.8% vs. 82.9%). Finally, seropositivity after two vaccine doses remains high (86.1%) even 15 years after the second dose. In conclusion, the research highlighted that vaccination against mumps reaches a good level of coverage only after two doses of vaccine persisting at high levels over 15 years and induces a more significant response in females.

Vaccination and Immunity toward Measles: A Serosurvey in Future Healthcare Workers.

Measles is a very contagious infectious disease, and vaccination is the only medical aid to counter the spread of the infection. The aim of this study was to evaluate the influence of vaccination schedule and type of vaccine, number of doses, and sex on the immune response. In a population of Italian medical students (8497 individuals born after 1980 with certificate of vaccination and quantitative measurement of antibodies against measles), the prevalence of positive antibodies to measles and antibody titer was measured. Vaccination schedule such as number of doses and vaccine type (measles alone or combined as measles, mumps and rubella (MMR)) and sex were the variables considered to influence the immune response. The vaccination schedule depends on the year of birth: students born before 1990 were prevalently vaccinated once and with measles vaccine alone (not as MMR). One dose of vaccine induces a significantly (p < 0.0001) higher positive response and antibody titer than two doses, in particular when measles alone is used (p < 0.0001). Females have a significantly higher percentage of positive response (p = 0.0001) than males but only when the MMR formulation was used. Multiple linear regression confirms that sex significantly influences antibody titer when only MMR is used, after one (p = 0.0002) or two (p = 0.0060) doses. In conclusion, vaccination schedule and, partially, sex influence immune response to measles vaccination. Most notably, the measles vaccine alone (one dose) is more effective than one and two doses of MMR.

Persistence of Anti-Hbs after up to 30 Years in Health Care Workers Vaccinated against Hepatitis B Virus.

The burden of hepatitis B virus (HBV) infection is a serious public health problem all over the world. Vaccination remains the most effective prevention measure, and safe and effective HBV vaccines have been available since 1982. Health care workers (HCWs) vaccinated against HBV and prospectively followed up for at least 14 years were classified by their antibody titers after primary vaccination as: poor responders (10-99 mIU/mL); moderate responders (100-999 mIU/mL); and good responders (≥1000 mIU/mL). The incidence of antibody loss was calculated for 1000 person-years and the anti-HBs persistence was calculated. The analysis concerned 539 HCWs: 494 good responders (91.7%); 37 moderate responders (6.9%); and eight poor responders (1.5%). The incidence of anti-HBs loss was 52.1 per 1000 person-years for the poor responders, 11.3 per 1000 person-years for the moderate responders, and 1.4 per 1000 person-years for the good responders. The mean persistence of anti-HBs differed significantly between the three groups, being: 19.2 years (95% CI: 15.6-22.8), 25.4 years (95% CI: 23.0-27.9), and 31.0 years (95% CI: 30.5-31.5) for the poor, moderate and good responders, respectively. In conclusion, our findings demonstrate a good persistence of protective anti-HBs titers in HCWs exposed to occupational risk for up to 30 years after a primary vaccination cycle (even without a booster dose) if their titer was initially higher than 100 mIU/mL.

COVID-19 challenge: proactive management of a Tertiary University Hospital in Veneto Region, Italy.

BACKGROUND: The aim of this study is to describe the successful emergency plan implemented by Padova University Hospital (AOUP) during the COVID-19 pandemic. METHODS: The emergency plan included early implementation of procedures aimed at meeting the increasing demand for testing and care while ensuring safe and timely care of all patients and guaranteeing the safety of healthcare workers. RESULTS: From 21 February to 1 May 2020, there were 3,862 confirmed cases of SARS-CoV-2 infection in the Province of Padua. A total of 485 patients were hospitalized in AOUP, of which 91 were admitted to the ICU; 12 .6% of admitted patients died. The average bed occupancy rate in the ICU was 61.1% (IQR 43.6%:77.4%). Inpatient surgery and inpatient admissions were kept for 76% and 74%, respectively, compared to March 2019. A total of 123,077 swabs were performed, 19.3% of which (23,725 swabs) to screen AOUP workers. The screening of all staff showed that 137 of 7,649 (1.8%) hospital workers were positive. No healthcare worker died. DISCUSSION: AOUP strategy demonstrated effective management of the epidemic thanks to the timely implementation of emergency procedures, a well-coordinated effort shared by all hospital Departments, and their continuous adjustment to the ongoing epidemic. Timely screening of all hospital workers proved to be particularly important to defend the hospital, avoiding epidemic clusters due to unknown positive cases.

Upper and Lower Respiratory Signs and Symptoms in Workers Occupationally Exposed to Flour Dust.

A group of 142 bakers was studied in order to investigate the relationship between higher/lower respiratory signs/symptoms and inflammation biomarkers and occupational exposure to flour dust. A complete upper and lower respiratory tract evaluation was performed. Seven percent of bakers complained of lower respiratory symptoms, while 22% of them complained of upper respiratory symptoms. Fifty five percent of the bakers were allergic, and 37.1% showed sensitization to occupational allergens. Abnormal spirometries were found in 15% of bakers, while fractional exhaled nitric oxide (FeNO) was above the normal reference in 24.5% of them. Moreover, 23.8% of bakers were found to be hyposmic. Population mean peak nasal inspiratory flow (PNIF) was in the normal range even if almost all the workers suffered from neutrophilic rhinitis at nasal cytology with the number of nasal neutrophils increasing with the increase of the duration of exposure to flour dust (p = 0.03). PNIF and FEV1 (forced expiratory volume in the 1st second) showed a positive correlation (p = 0.03; r = 0.19). The Tiffeneau index decreased with the increase of dust (p = 0.017). A similar result was obtained once we divided our population into smokers and non-smokers (p = 0.021). Long-term exposure to bakery dusts can lead to a status of minimal nasal inflammation and allergy.

Retrospective Analysis of a Modified Organizational Model to Guarantee CT Workflow during the COVID-19 Outbreak in the Tertiary Hospital of Padova, Italy.

At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) outbreak in Italy, the cluster of Vò Euganeo was managed by the University Hospital of Padova. The Department of Diagnostic Imaging (DDI) conceived an organizational approach based on three different pathways for low-risk, high-risk, and confirmed Coronavirus Disease 19 (COVID-19) patients to accomplish three main targets: guarantee a safe pathway for non-COVID-19 patients, ensure health personnel safety, and maintain an efficient workload. Thus, an additional pathway was created with the aid of a trailer-mounted Computed Tomography (CT) scanner devoted to positive patients. We evaluated the performance of our approach from February 21 through April 12 in terms of workload (e.g., number of CT examinations) and safety (COVID-19-positive healthcare workers). There was an average of 72.2 and 17.8 COVID-19 patients per day in wards and the Intensive Care Unit (ICU), respectively. A total of 176 high-risk and positive patients were examined. High Resolution Computed Tomography (HRCT) was one of the most common exams, and 24 pulmonary embolism scans were performed. No in-hospital transmission occurred in the DDI neither among patients nor among health personnel. The weekly number of in-patient CT examinations decreased by 27.4%, and the surgical procedures decreased by 29.5%. Patient screening and dedicated diagnostic pathways allowed the maintenance of high standards of care while working in safety.

Occupational Exposure to Flour Dust. Exposure Assessment and Effectiveness of Control Measures.

The adverse effects associated with exposure to flour dust have been known since the 1700s. The aim of the study was to assess the occupational exposure to flour dust in Italian facilities, identify the activities characterized by the highest exposure, and provide information to reduce workers' exposure. The study was performed in different facilities such as flourmills (n = 2), confectioneries (n = 2), bakeries (n = 24), and pizzerias (n = 2). Inhalable flour dust was assessed by personal and area samplings (n = 250) using IOM (Institute of Occupational Medicine) samplers. The results showed personal occupational exposure to flour dust over the American Conference of Governmental Industrial Hygiene (ACGIH) and the Scientific Committee on Occupational Exposure Limit (SCOEL) occupational limits (mean 1.987 mg/m3; range 0.093-14.055 mg/m3). The levels were significantly higher for dough makers in comparison to the dough formers and packaging area subjects. In four bakeries the industrial hygiene surveys were re-performed after some control measures, such as installation of a sleeve to the end of pipeline, a lid on the mixer tub or local exhaust ventilation system, were installed. The exposure levels were significantly lower than those measured before the introduction of control measures. The exposure level reduction was observed not only in the dough making area but also in all bakeries locals.

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.