Estimating thoracic kyphosis without information on upper thoracic kyphosis: an observational study on 455 patients examined by EOS imaging.

BACKGROUND: Physiological thoracic kyphosis (TK) allows sagittal balance of human body. Unlike lumbar lordosis (LL), TK has been relatively neglected in the literature. EOS is an imaging technique employing high-sensitivity xenon particles, featured by low-dose exposure combined with high accuracy compared to conventional radiography. The aim of this study was to investigate predictors of TK in patients with phyiological spine morphology using EOS imaging. METHODS: EOS images of 455 patients without spinal anomalies were retrospectively assessed for TK (T1- T12), upper thoracic kyphosis (UTK, T1-T5), lower thoracic kyphosis (LTK, T5-T12), LL (L1-S1) and pelvic incidence (PI). The latter curves were measured by two researchers separately and the average of the two measurements was used for further analysis. Spearman non-parametric correlation was estimated for age, PI, LL, LTK, UTK and TK. Multiple robust linear regression analysis was employed to estimate TK, controlling for the effect of age, sex, LL and LTK. RESULTS: The mean age of patients was 28.3 ± 19.2 years and 302 (66.4%) of them were females. The mean TK, UTK and LTK was 45.5° ± 9.3, 16 ± 7.4° and 29.7° ± 8.9, respectively. The mean UTK in people under 40 years of age was 17.0° ± 7.2, whereas for patients 40+ years old it was 13.6° ± 7.4. At univariable analysis TK positively correlated with UTK (p<0.001), LTK (p<0.001) an LL (p<0.001). At multivariable linear regression TK increased with LTK (RC = 0.67; 95%CI: 0.59; 0.75) or LL (RC = 0.12; 95%CI: 0.06; 0.18), whereas it decreased with age (RC = -0.06; 95%CI: -0.09;-0.02). CONCLUSION: If EOS technology is available, the above linear regression model could be used to estimate TK based upon information on age, sex, LL and LTK. Alternatively, TK could be estimated by adding to LTK 17.0° ± 7.4 for patients < 40 years of age, or 13.6° ± 7.4 in patients 40 + years old. The evidence from the present study may be used as reference for research purposes and clinical practice, including spine examination of particular occupational categories or athletes.

COVID-19 in City Council Civil Servants, 1 March 2020-31 January 2023: Risk of Infection, Reinfection, Vaccine Effectiveness and the Impact of Heterologous Triple Vaccination.

Background: The risk of COVID-19 increases in any occupation entailing intense social interactions. This study aimed to investigate the impact of COVID-19 among civil servants of Trieste city council (northeastern Italy) over the entire pandemic. Methods: The crude incidence rate of COVID-19 was estimated from 1 March 2020 to 31 January 2023 by explanatory factors, expressing the estimate as COVID-19 events x 10,000 person-days (P-d) at risk. A multivariable Cox proportional hazard regression model was fitted to examine the risk of primary COVID-19 infection and reinfections, reporting adjusted hazard ratios (aHR) with 95% confidence interval (95% CI). Results: The cohort of Trieste city council was mainly composed of administrative clerks (48.5%), nursery teachers (33%), technicians (9.9%) and local police officers (8.5%). Between 1 March 2020 and 31 January 2023, 1444 (62.4%) employees tested positive for SARS-CoV-2 at least once and 18.1% (=262/1444) at least twice. By the end of this study, 55% (N = 1272) of employees had received at least three doses of COVID-19 vaccine, whereas 19.7% (N = 457) remained unvaccinated. At multiple Cox regression analysis, the adjusted risk of primary COVID-19 events during the entire study period increased in employees aged 40-49 years (aHR = 1.65; 95% CI: 1.01; 2.71), females (aHR = 1.28; 95%CI: 1.12; 1.45), local police officers (aHR = 1.82; 95%CI: 1.50; 2.22) and nursery teachers (aHR = 1.27; 95%CI: 1.13; 1.43). However, whilst the risk of primary infections in police officers increased already during the Alpha transmission period (aHR = 6.82; 95%CI: 4.48; 10.40), progressively reducing across subsequent variants, for nursery teachers, it increased during the Delta wave (aHR = 2.42; 1.70; 3.44), reducing with Omicron (aHR = 1.23; 95%CI: 1.07; 1.40). Compared to unvaccinated colleagues, during the entire study period the risk of primary infections was significantly lower in employees immunized with three (aHR = 0.42; 95%CI: 0.36; 0.47) or four (aHR = 0.30; 95%CI: 0.23; 0.40) doses of COVID-19 vaccine, for a vaccine effectiveness (VE) of 58% and 70%, respectively. The protective effect of vaccination against primary infections was confirmed in the sub-group analysis by main pandemic waves, for a VE of 75% for one dose against 99% for two doses during the Alpha transmission period, slightly reducing to 59% and 70% in Delta time, respectively. During the Omicron wave, the risk of primary SARS-CoV-2 infections diminished significantly with three (aHR = 0.42; 95%CI: 0.36; 0.49) or four vaccine doses (aHR = 0.09; 95%CI: 0.05; 0.16), for a VE of 58% and 91%, respectively. Moreover, the risk of primary SARS-CoV-2 reinfections during the entire study period reduced with one (aHR = 0.47; 95%CI: 0.27; 0.82), two (aHR = 0.42; 95%CI: 0.30; 0.58), three (aHR = 0.32; 95%CI: 0.24; 0.44) or four vaccine doses (aHR = 0.14; 95%CI: 0.05; 0.46), for a VE of 53%, 58%, 68% and 86% against reinfections, respectively. No significant difference in VE was associated with heterologous versus homologous triple vaccination, both against primary infections or reinfections. Conclusions: Primary SARS-CoV-2 infections were more likely among nursery teachers and local police officers. The risk of both primary infections and reinfections reduced with higher number of doses of COVID-19 vaccine, regardless of the pandemic wave. Since city council civil servants were swab tested on demand or for contact tracing, the estimation of COVID-19 risk and VE largely missed aymptomatic SARS-CoV-2 infections. On the one hand, the present study confirmed the protective effect of COVID-19 vaccination against symptomatic SARS-CoV-2 infections; on the other hand, it highlighted not only the importance of continuous booster doses to keep up the humoral immunity over time but also the importance of updated vaccine formulations to prevent and control the spread of a highly mutable virus. Moreover, the protective effect of the first two doses against reinfections confirmed the efficacy of hybrid immunity during Omicron time.

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.

Nano and microparticle drug delivery systems for the treatment of Brucella infections.

Nano-based drug delivery systems are increasingly used for diagnosis, prevention and treatment of several diseases, thanks to several beneficial properties, including the ability to target specific cells or organs, allowing to reduce treatment costs and side effects frequently associated with chemotherapeutic medications, thereby improving treatment compliance of patients. In the field of communicable diseases, especially those caused by intracellular bacteria, the delivery of antibiotics targeting specific cells is of critical importance to maximize their treatment efficacy. Brucella melitensis, an intracellular obligate bacterium surviving and replicating inside macrophages is hard to be eradicated, mainly because of the low ability of antibiotics to enter these phagocityc cells . Although different antibiotics regimens including gentamicin, doxycycline and rifampicin are in fact used against the Brucellosis, no efficient treatment has been attained yet, due to the intracellular life of the respective pathogen. Nano-medicines responding to environmental stimuli allow to maximize drug delivery targeting macropages, thereby boosting treatment efficacy. Several drug delivery nano-technologies, including solid lipid nanoparticles, liposomes, chitosan, niosomes, and their combinations with chitosan sodium alginate can be employed in combination of antibiotics to successfully eradicate Brucellosis infection from patients.

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.

Maintaining Cross-Border Cargo Movements Between Jordan and Saudi Arabia During the COVID-19 Pandemic.

One of Jordan's essential border crossings, the Al-Omari border crossing, is 1 of 3 land crossings between Jordan and Saudi Arabia and is located 160 km west of the capital city of Amman. Given its economic importance and essential role in the functioning of food supply networks across the region, Jordan undertook evidence-driven actions to keep the border crossing safely open during the initial phase of the COVID-19 pandemic. Cross-border coordination and collaboration, specifically with international contact tracing and case management, have been critical elements of Jordan's response. While several bottlenecks and delays led to documented clusters of infections among truck drivers, this case study illustrates the use of evidence to mitigate disease exposure and spread. Plans to manage public health threats need to consider sustainable strengthened surveillance and laboratory capacities coupled with efficient cross-border communication and coordination plans implemented across multiple sectors engaged in cross-country health.

SARS-CoV-2 Reinfections in Health-Care Workers, 1 March 2020-31 January 2023.

Objective: To study SARS-CoV-2 reinfections in health-care workers (HCWs) of the University Health Agency Giuliano-Isontina (ASUGI), covering the provinces of Trieste and Gorizia (northeastern Italy) routinely screened for SARS-CoV-2 via nasopharyngeal swab. Design: Cohort study of HCWs (N = 8205) followed since the start of the pandemic (1 March 2020) through 31 January 2023. The risk of reinfection during the Omicron transmission period (after 30 November 2021) among HCWs previously infected by SARS-CoV-2 was estimated based on days since last dose of COVID-19 vaccine received, adjusting for age, sex, job task, workplace, number of doses of COVID-19 vaccines and number of swab tests performed. In the crude as well as adjusted incidence rate analysis, reinfections occurring 15+ days after a first dose of COVID-19 vaccine or 8+ days following a second or more dose were counted. Results: In a highly vaccinated population, during the entire study period (1 March 2020-31 January 2023) 5253 HCWs incurred at least one SARS-CoV-2 infection, 4262 HCWs were infected only once, and 1091 were reinfected. Reinfections almost entirely (99.1% = 1071/1091) occurred after 30 November 2021, peaking in July 2022 (N = 161). Six hundred eighty-three reinfections followed a pre-Omicron primary event against 408 reinfections following an Omicron event. Reinfections during the Omicron transmission period occurred a mean of 400 ± 220 days after primary SARS-CoV-2 infection; 512 ± 205 days following a pre-Omicron primary event, as opposed to 218 ± 74 days after an Omicron primary infection. Thirty-four hospitalizations were observed, all before the Omicron wave, following 18 (0.4%) primary SARS-CoV-2 infections and 16 (1.5%) reinfections. By excluding events occurring <15 days after a first dose or <8 days after a further dose of COVID-19 vaccine, 605 reinfections followed a pre-Omicron primary event (raw incidence = 1.4 × 1000 person-days) against 404 after a primary Omicron infection (raw incidence = 0.3 × 1000 person-days). Apart from nurse aids (slightly enhanced biological risk) and academic HCWs (remarkably lower risk with pre-Omicron primary events), the effect of occupation in terms of job task and workplace was marginal. Furthermore, whilst the risk of reinfection was lower in males and HCWs < 60 years old following a pre-Omicron primary infection, HCWs aged 30-50 were more likely to be infected after an Omicron primary event. Regardless of timeline of primary SARS-CoV-2 event, the risk of reinfection decreased with higher number of doses of COVID-19 vaccines, being lowest after the second booster. In particular, VE was 16% for one dose, 51% for two doses, 76% for the booster and 92% for the second booster with a pre-Omicron primary SARS-CoV-2 event. The latter figures increased to 72%, 59%, 74% and 93%, respectively, with Omicron primary infections. Conclusions: SARS-CoV-2 reinfections were frequent during the Omicron transmission period, though featured by mild or no symptoms. Whilst the impact of occupation on biological risk was relatively marginal, COVID-19 vaccination had the strongest protective effect against reinfection, with a 93% VE by second booster following an Omicron primary infection.

Efficacy of ozone therapy on visual evoked potentials in diabetic patients.

BACKGROUND: The involvement of the central nervous system is a frequent yet underestimated complication of diabetes mellitus. Visual evoked potentials (VEP) are a simple, sensitive, and noninvasive method for detecting early alterations in central optic pathways. The objective of this paralleled randomized controlled trial was to evaluate the impact of ozone therapy on visual pathways in diabetic patients. METHODS: Sixty patients with type 2 diabetes visiting clinics of Baqiyatallah university in Tehran (Iran) hospital were randomly assigned to two experimental groups: Group 1 (N = 30) undergoing a cycle of 20 sessions of systemic oxygen-ozone therapy in addition to standard therapy for metabolic control; Group 2 (N = 30)-serving as control-receiving only standard therapy against diabetes. The primary study endpoints were two VEP parameters; P100 wave latency and P100 amplitude at 3 months. Moreover, HbA1c levels were measured before the start of treatment and three months later as secondary study endpoint. RESULTS: All 60 patients completed the clinical trial. P100 latency significantly reduced at 3 months since baseline. No correlation was found between repeated measures of P100 wave latency and HbA1c (Pearson's r = 0.169, p = 0.291). There was no significant difference between baseline values and repeated measures of P100 wave amplitude over time in either group. No adverse effects were recorded. CONCLUSIONS: Ozone therapy improved the conduction of impulses in optic pathways of diabetic patients. The improved glycemic control following ozone therpay may not fully explain the reduction of P100 wave latency though; other mechanistic effects of ozone may be involved.

Molnupiravir, Nirmatrelvir/Ritonavir, or Sotrovimab for High-Risk COVID-19 Patients Infected by the Omicron Variant: Hospitalization, Mortality, and Time until Negative Swab Test in Real Life.

Background. Several drugs which are easy to administer in outpatient settings have been authorized and endorsed for high-risk COVID-19 patients with mild-moderate disease to prevent hospital admission and death, complementing COVID-19 vaccines. However, the evidence on the efficacy of COVID-19 antivirals during the Omicron wave is scanty or conflicting. Methods. This retrospective controlled study investigated the efficacy of Molnupiravir or Nirmatrelvir/Ritonavir (Paxlovid®) or Sotrovimab against standard of care (controls) on three different endpoints among 386 high-risk COVID-19 outpatients: hospital admission at 30 days; death at 30 days; and time between COVID-19 diagnosis and first negative swab test result. Multivariable logistic regression was employed to investigate the determinants of hospitalization due to COVID-19-associated pneumonia, whereas time to first negative swab test result was investigated by means of multinomial logistic analysis as well as Cox regression analysis. Results. Only 11 patients (overall rate of 2.8%) developed severe COVID-19-associated pneumonia requiring admission to hospital: 8 controls (7.2%); 2 patients on Nirmatrelvir/Ritonavir (2.0%); and 1 on Sotrovimab (1.8%). No patient on Molnupiravir was institutionalized. Compared to controls, hospitalization was less likely for patients on Nirmatrelvir/Ritonavir (aOR = 0.16; 95% CI: 0.03; 0.89) or Molnupiravir (omitted estimate); drug efficacy was 84% for Nirmatrelvir/Ritonavir against 100% for Molnupiravir. Only two patients died of COVID-19 (rate of 0.5%), both were controls, one (a woman aged 96 years) was unvaccinated and the other (a woman aged 72 years) had adequate vaccination status. At Cox regression analysis, the negativization rate was significantly higher in patients treated with both antivirals-Nirmatrelvir/Ritonavir (aHR = 1.68; 95% CI: 1.25; 2.26) or Molnupiravir (aHR = 1.45; 95% CI: 1.08; 1.94). However, COVID-19 vaccination with three (aHR = 2.03; 95% CI: 1.51; 2.73) or four (aHR = 2.48; 95% CI: 1.32; 4.68) doses had a slightly stronger effect size on viral clearance. In contrast, the negativization rate reduced significantly in patients who were immune-depressed (aHR = 0.70; 95% CI: 0.52; 0.93) or those with a Charlson index ≥5 (aHR = 0.63; 0.41; 0.95) or those who had started the respective treatment course 3+ days after COVID-19 diagnosis (aOR = 0.56; 95% CI: 0.38; 0.82). Likewise, at internal analysis (excluding patients on standard of care), patients on Molnupiravir (aHR = 1.74; 95% CI: 1.21; 2.50) or Nirmatrelvir/Ritonavir (aHR = 1.96; 95% CI: 1.32; 2.93) were more likely to turn negative earlier than those on Sotrovimab (reference category). Nonetheless, three (aHR = 1.91; 95% CI: 1.33; 2.74) or four (aHR = 2.20; 95% CI: 1.06; 4.59) doses of COVID-19 vaccine were again associated with a faster negativization rate. Again, the negativization rate was significantly lower if treatment started 3+ days after COVID-19 diagnosis (aHR = 0.54; 95% CI: 0.32; 0.92). Conclusions. Molnupiravir, Nirmatrelvir/Ritonavir, and Sotrovimab were all effective in preventing hospital admission and/or mortality attributable to COVID-19. However, hospitalizations also decreased with higher number of doses of COVID-19 vaccines. Although they are effective against severe disease and mortality, the prescription of COVID-19 antivirals should be carefully scrutinized by double opinion, not only to contain health care costs but also to reduce the risk of generating resistant SARS-CoV-2 strains. Only 64.7% of patients were in fact immunized with 3+ doses of COVID-19 vaccines in the present study. High-risk patients should prioritize COVID-19 vaccination, which is a more cost-effective approach than antivirals against severe SARS-CoV-2 pneumonia. Likewise, although both antivirals, especially Nirmatrelvir/Ritonavir, were more likely than standard of care and Sotrovimab to reduce viral shedding time (VST) in high-risk SARS-CoV-2 patients, vaccination had an independent and stronger effect on viral clearance. However, the effect of antivirals or COVID-19 vaccination on VST should be considered a secondary benefit. Indeed, recommending Nirmatrelvir/Ritonavir in order to control VST in high-risk COVID-19 patients is rather questionable since other cheap, large spectrum and harmless nasal disinfectants such as hypertonic saline solutions are available on the market with proven efficacy in containing VST.

Oncolytic viruses: A novel treatment strategy for breast cancer.

Breast cancer, an unceasingly occurring neoplasm, is one of the major determinants of mortality in women. Several ineffective attempts have been pursued using with conventional therapies against breast cancer. Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses. Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells. Several different DNA- and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus, herpes virus, vaccinia, reovirus, Newcastle Disease virus, measles virus and vesicular stomatitis virus. This review aims to summarize the viro-therapeutical agents against breast malignancies. Key Scientific Concepts of Review: In this review paper, we proposed a new strategy to virus's combinatorial treatments using several kinds of transgenes and drugs. These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.

Supporting the Aspecific Physiological Defenses of Upper Airways against Emerging SARS-CoV-2 Variants.

The rapid rollout of COVID-19 vaccines in 2021 sparked general optimism toward controlling the severe form of the disease, preventing hospitalizations and COVID-19-associated mortality, and the transmissibility of SARS-CoV-2 infection [...].

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020-2 April 2022.

Background: University workers undergo intense social interactions due to frequent contact with students and colleagues and lectures in crowdy conditions. The aim of our study was to assess the incidence of COVID-19 infection and vaccine effectiveness in a cohort of workers of the University of Trieste from 1 March 2020 (start of the pandemic) through 2 April 2022. Methods: The University of Trieste implemented a number of public health policies to contain the spread of SARS-CoV-2 on the campus, including prompt contact tracing, enhanced ventilation of all premises, fomites disinfection and mandatory use of face masks indoors. In compliance with the surveillance protocol of the local public health department, university personnel were tested for SARS-CoV-2 by polymerase chain reaction (PCR) on a nasopharyngeal swab on demand, in the event of symptoms consistent with COVID-19 or for contact tracing, following close contact with a confirmed COVID-19 case. The incidence rates of SARS-CoV-2 infections were estimated as number of cases by number of person-days (p-d) at risk. Multivariable Cox proportional hazard regression model was employed to investigate the risk of primary COVID-19 infection, controlling for a number of potential confounders and expressing the risk as the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI). Results: The incidence of SARS-CoV-2 infection among university staff was lower than that of healthcare workers (HCWs) of the same area. Compared to unvaccinated colleagues (6.55 × 10,000 p-d), the raw incidence of SARS-CoV-2 infection was higher among university workers immunized with one (7.22 × 10,000 p-d) or two (7.48 × 10,000 p-d) doses of COVID-19 vaccines, decreasing in those receiving the booster (1.98 × 1000 p-d). The risk of infection increased only in postgraduate medical trainees (aHR = 2.16; 95% CI: 1.04; 4.48), though this was limited to the Omicron transmission period. After the implementation of the national vaccination campaign against COVID-19, workers immunized with the booster were less likely than unvaccinated workers to be infected by SARS-CoV-2 both before (aHR = 0.10; 95% CI: 0.06; 0.16) and after (aHR = 0.37; 95% CI: 0.27; 0.52) the Omicron transmission period. Vaccine effectiveness of the booster was 90% (=(1-0.10) × 100) before versus 63% (=(1-0.37) × 100) during the Omicron wave, without a significant difference between homologous (three doses of m-RNA vaccines) and heterologous immunization (first two doses of Vaxzevria followed by a third dose of m-RNA vaccine). Conclusions: The incidence of SARS-CoV-2 infection in university staff was lower than that of HCWs of ASUGI, likely because the testing-on-demand schedule inevitably missed the vast majority of asymptomatic infections. Therefore, the observed significantly protective effect of the booster dose in university personnel referred to symptomatic SARS-CoV-2 infections. The infection prevention and control policies implemented by the University of Trieste managed to equalize the biological risk between administrative and teaching staff.

Concentration of mercury in human hair and associated factors in residents of the Gulf of Trieste (North-Eastern Italy).

The Gulf of Trieste (Northern Adriatic Sea, Italy) is the coastal area of the Mediterranean Sea most highly contaminated by mercury (Hg) due to fluvial inputs from the Isonzo/Soca River system, draining over 500 years' worth of cinnabar extraction activity from the Idrija mining district (Western Slovenia). The aim of this research is to investigate the concentration of Hg in hair samples taken from the general population of the Friuli Venezia Giulia (FVG) Region coastal area, as a marker of chronic exposure to Hg. Three hundred and one individuals - 119 males and 182 females - were recruited by convenience sampling in Trieste in September 2021. An amount of approximately 100 mg of hair was collected from the occipital scalp of each participant to measure the respective Hg concentrations (expressed as mg/kg). Moreover, participants completed a self-report questionnaire collecting extensive socio-demographic and life-style information. A multiple linear regression analysis was employed to investigate factors associated with increased levels of Hg concentration in hair. A mean Hg concentration in hair of 1.63 mg/kg was found, slightly above the 1.0 mg/kg threshold recommended by the WHO for pregnant women and children, although still well below the no observed adverse effects level (NOAEL) of 10 mg/kg. Among respondents, 55.6% showed a Hg concentration in hair > 1 mg/kg, 22.9% > 2 mg/kg, and 2 participants exhibited Hg levels > 10 mg/kg. The adjusted mean hair Hg level increased in those subjects who reported a preference for shellfish/crayfish/mollusks (RC = 0.35; 95%CI: 0.16; 0.55), whereas it decreased in those who reported a preference for frozen fish (RC = -0.23; 95%CI: - 0.39; - 0.06). Though a risk alert for Hg exposure for coastal residents from FVG is deemed unnecessary at this time, it is recommended that pregnant women limit their ingestion of locally caught fish to < 4 servings/month.

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.

Primary SARS-CoV-2 Infections, Re-infections and Vaccine Effectiveness during the Omicron Transmission Period in Healthcare Workers of Trieste and Gorizia (Northeast Italy), 1 December 2021-31 May 2022.

Objective: To evaluate the incidence of primary and recurrent COVID-19 infections in healthcare workers (HCWs) routinely screened for SARS-CoV-2 by nasopharyngeal swabs during the Omicron wave. Design: Dynamic Cohort study of HCWs (N = 7723) of the University Health Agency Giuliano Isontina (ASUGI), covering health services of the provinces of Trieste and Gorizia (Northeast Italy). Cox proportional hazard model was employed to estimate the risk of primary as well as recurrent SARS-CoV-2 infection from 1 December 2021 through 31 May 2022, adjusting for a number of confounding factors. Results: By 1 December 2021, 46.8% HCWs of ASUGI had received the booster, 37.2% were immunized only with two doses of COVID-19 vaccines, 6.0% only with one dose and 10.0% were unvaccinated. During 1 March 2020-31 May 2022, 3571 primary against 406 SARS-CoV-2 recurrent infections were counted among HCWs of ASUGI, 59.7% (=2130/3571) versus 95.1% (=386/406) of which occurring from 1 December 2021 through 31 May 2022, respectively. All HCWs infected by SARS-CoV-2 during 1 December 2021 through 31 May 2022 presented mild flu-like disease. Compared to staff working in administrative services, the risk of primary as well as recurrent SARS-CoV-2 infection increased in HCWs with patient-facing clinical tasks (especially nurses and other categories of HCWs) and in all clinical wards but COVID-19 units and community health services. Regardless of the number of swab tests performed during the study period, primary infections were less likely in HCWs immunized with one dose of COVID-19 vaccine. By contrast, the risk of SARS-CoV-2 re-infection was significantly lower in HCWs immunized with three doses (aHR = 0.58; 95%CI: 0.41; 0.80). During the study period, vaccine effectiveness (VE = 1-aHR) of the booster dose declined to 42% against re-infections, vanishing against primary SARS-CoV-2 infections. Conclusions: Though generally mild, SARS-CoV-2 infections and re-infections surged during the Omicron transmission period. Compared to unvaccinated colleagues, the risk of primary SARS-CoV-2 infection was significantly lower in HCWs immunized just with one dose of COVID-19 vaccines. By Italian law, HCWs immunized only with one dose were either suspended or re-assigned to job tasks not entailing patient facing contact; hence, while sharing the same biological risk of unvaccinated colleagues, they arguably had a higher level of protection against COVID-19 infection. By contrast, SARS-CoV-2 re-infections were less likely in HCWs vaccinated with three doses, suggesting that hybrid humoral immunity by vaccination combined with natural infection provided a higher level of protection than vaccination only. In this stage of the pandemic, where SARS-CoV-2 is more infectious yet much less pathogenic, health protection measures in healthcare premises at higher biological risk seem the rational approach to control the transmission of the virus.