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

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

Occupational contact dermatitis in a gender perspective: North East Italian data 1996-2016.

BACKGROUND: Occupational contact dermatitis (OCD) ranks high among occupational diseases in Europe, but little is known as regards OCD and jobs in a gender perspective. OBJECTIVES: To evaluate sex prevalence of OCD according to occupational sectors and agents involved. 27381 patients (1996-2016) with suspected irritant/allergic contact dermatitis (ICD-ACD) were evaluated in North-Eastern Italy. Each patient underwent: a standardized questionnaire, a dermatologist/occupational physician evaluation and a patch test. RESULTS: Females were younger at diagnosis (35.2 ± 11.6 years vs 37.7 ± 12.6 in males, p< 0.001) and had a lower ICD prevalence (OR 0.58, C.I. 95% 0.51 - 0.66, p < 0.001). Job categories most involved differed between sexes, with highest rank for healthcare professionals in females and machinery mechanics and filters for males. In females ACD percentage was higher in all job categories. CONCLUSIONS: OCD characteristics differ between sexes, according to intrinsic and extrinsic factors. Use of personal care products, housekeeping products and outdoor work activities may account for different sensitization profiles.

Characteristics and incidence of contact dermatitis among hairdressers in north-eastern Italy.

BACKGROUND: Hairdressers are at high risk of contact dermatitis (CD) due to skin exposure to numerous irritants and haptens in hair products in combination with frequent wet work. OBJECTIVES: To investigate the characteristics and incidence of CD among hairdressers in north-eastern Italy. METHODS: A total of 324 hairdressers who had been examined and patch tested in north-eastern Italy from 1996 to 2016 were retrospectively identified, and compared with 9669 matched controls. Sensitization to allergens of the hairdressing series was analysed among hairdressers attending an occupational medicine clinic in Trieste, Italy. Incidence data were calculated from 1999 to 2016. RESULTS: Sensitization to p-phenylenediamine, thiuram mix, and N-isopropyl-N'-phenyl-p-phenylenediamine was significantly associated with hairdressing and with hand/forearms dermatitis. Frequent sensitizers from hairdressing series were ammonium persulfate, toluene-2,5-diamine, and p-aminobenzene. The overall incidence of CD declined from 2003 (31.7 cases/10 000 workers) to 2016 (20.8 cases/10 000 workers). CONCLUSIONS: Sensitization to several haptens was significantly associated with hairdressing. The incidence of CD among hairdressers in north-eastern Italy has declined in recent years, but is still high. Preventive efforts are needed to reduce the burden of CD in this professional group.

Sensitization to nickel in the Triveneto region: Temporal trend after European Union regulations.

Highlights After the introduction of the EU regulatory interventions, nickel sensitization decreased significantly in the group of females aged ≤25 years. Women born between 1966 and 1975 presented the higheest prevalence of sensitization to nickel, then prevalence of sensitization gradually decreased with a minimum in more recent years. Nickel sensitization is higher in Italian patients compared to people living in other EU coutries. Additional interventions are needed to address nickel sensitization.

Occupational contact dermatitis in Triveneto: Analysis of patch test data of the North Eastern Italian Database from 1996 to 2016.

BACKGROUND: Occupational contact dermatitis (OCD) is frequent in the workplace. OBJECTIVES: To provide recent data on the epidemiology of OCD in Italy. METHODS: This multicenter retrospective study, conducted from 1996 to 2016, included patients with suspected allergic contact dermatitis (ACD) patch tested in the departments comprising the North-East Italy Contact Dermatitis Group. RESULTS: We studied 18 859 workers with a diagnosis of contact dermatitis (CD), of which 10.4% were recognized as being of professional origin. OCD declined from 1996 to 2011-2013 and increased in 2014-2016. The overall prevalence of both CD and OCD was higher in women compared to men, but the share of OCD of the total CD was greater for men compared to women. A history of atopic dermatitis was less frequent in workers with OCD than in non-OCD patients (5.8% vs 8.6%). Hairdressers were the youngest profession (27.1 ± 11.7 years). Hands were the primary site of involvement in patients with OCD (76.6%). The five highest risk occupations for OCD were hairdressers, cooks, metalworkers, chemical industry workers, and construction workers. CONCLUSIONS: OCDs have a relevant impact in our region, mainly for five job categories, and the increase in the last 3 years suggests the need to improve preventive measures.

Cerium Oxide Nanoparticles Absorption through Intact and Damaged Human Skin.

Cerium oxide (CeO2) nanoparticles (NPs) are used in polishing products and absorbents, as promoters in wound healing, and as organopesticide decontaminants. While systemic bioaccumulation and organ toxicity has been described after inhalation, data on CeO2 NPs' transdermal permeation are lacking. Our study was an in vitro investigation of the permeation of 17-nm CeO2 NPs dispersed in synthetic sweat (1 g L-1) using excised human skin on Franz cells. Experiments were performed using intact and needle-abraded skin, separately. The average amount of Ce into intact and damaged skin samples was 3.64 ± 0.15 and 7.07 ± 0.78 µg cm-2, respectively (mean ± SD, p = 0.04). Ce concentration in the receiving solution was 2.0 ± 0.4 and 3.3 ± 0.7 ng cm-2 after 24 h (p = 0.008). The Ce content was higher in dermal layers of damaged skin compared to intact skin (2.93 ± 0.71 µg cm-2 and 0.39 ± 0.16 µg cm-2, respectively; p = 0.004). Our data showed a very low dermal absorption and transdermal permeation of cerium, providing a first indication of Ce skin uptake due to contact with CeO2.

Sensitization to, and allergic contact dermatitis caused by, colophonium in north-eastern Italy in 1996 to 2016 with a focus on occupational exposures.

BACKGROUND: Colophonium is a natural substance derived from Pineaceae trees. It is used in a wide range of consumer and occupational products because of its tackiness, and is a known sensitizer. OBJECTIVES: To analyse the temporal trend of contact allergy to colophonium in north-eastern Italy, and to evaluate the associations with occupations in our geographical area. METHODOLOGY: From 1996 to 2016, 27 381 patients with suspected allergic contact dermatitis were patch tested in north-eastern Italy. Individual characteristics were documented by use of a standardized questionnaire in 6 departments of dermatology or occupational medicine. RESULTS: The overall prevalence of colophonium sensitization was 1.67%; the prevalence was significantly higher in women (1.75%) than in men (1.49%). No significant differences among departments were observed. We found significant associations between colophonium sensitization and being a student (odds ratio [OR] 4.64; 95% confidence interval [CI]: 1.04-20.6), being a farmer or fishermen (OR 3.63; 95%CI: 1.21-10.84), being a housekeeper (OR 2.02; 95%CI: 1.08-3.77), and being retired (OR 2.06; 95%CI: 1.08-3.92). CONCLUSION: Our study showed that contact allergy to colophonium is still relevant in north-eastern Italy. The frequency of sensitization has dropped significantly over a period of 10 years, but students and farmers/fishermen still have sensitization prevalences above 3.5%. Our results are in line with European data.

[Guidelines for occupational exposures to mechanical vibration.] / I valori guida nella valutazione del rischio da vibrazioni meccaniche.

OBJECTIVES: In this study, the daily exposure action values (EAV) and the daily exposure limit values (ELV) for hand-transmitted vibration (HTV) and whole-body vibration (WBV), established by the EU Directive 2002/44/EC and the Italian Decree 81/2008, and expressed in terms of 8-hr frequency weighted r.m.s. acceleration magnitude, are discussed upon consideration of the findings of experimental and epidemiological studies. METHODS: There is some epidemiological support for the EAV A(8) of 2.5 ms-2 r.m.s. and the ELV A(8) of 5 ms-2 r.m.s. for HTV, at least for the vascular component (secondary Raynaud's phenomenon) of the hand-arm vibration syndrome. RESULTS: There is some experimental evidence for the EAV A(8) of 0.5 ms-2 r.m.s. for WBV, while there is neither biodynamic nor epidemiological validation for the ELV A(8) of 1.15 ms-2 r.m.s. for WBV, this latter lowered to 1 ms-2 r.m.s. in the Italian legislation.

An overview of low back pain and occupational exposures to whole-body vibration and mechanical shocks.

This paper offers an overview of the relation of low back pain (LBP) to occupational exposures to whole-body vibration (WBV) and mechanical shocks. LBP is a condition of multifactorial origin and is a very common health problem in the general population. Among occupational risk factors, epidemiological studies of driving occupations have provided evidence for strong associations between LBP and occupational exposures to WBV and mechanical shocks. Since it is hard to separate the contribution of WBV exposure to disorders in the lower back from that of other individual, ergonomic or psychosocial risk factors, a quantitative exposure-response relationship for WBV cannot be outlined precisely. Experimental research has provided biodynamic support to the findings of epidemiological studies, showing that in controlled laboratory conditions exposure to WBV can cause mechanical overload to the human spine. The EU Directive on mechanical vibration has established daily exposure action and limit values to protect the workers against the risk from WBV. There is some evidence that the EU exposure limit values are excessive, so much so that an elevated risk of LBP has been found for WBV exposures beneath the EU limit values. In the Italian arm of the EU VIBRISKS prospective cohort study of professional drivers, measures of internal lumbar load (compressive and shear peak forces), calculated by means of anatomy-based finite-element models, were found better predictors of the occurrence over time of low back disorders than the metrics of external exposure suggested by the EU Directive on mechanical vibration. Further biodynamic and epidemiological studies are needed to validate the findings of the VIBRISKS study.

A longitudinal study of neck and upper limb musculoskeletal disorders and alternative measures of vibration exposure.

OBJECTIVE: To investigate the exposure-response relationships between alternative frequency weightings of hand-transmitted vibration (HTV) and neck and upper limb musculoskeletal disorders (MSDs) in a cohort of HTV workers. METHODS: In a three-year longitudinal study, the occurrence of neck and upper limb MSDs was investigated in 249 HTV workers and 138 control men. In the HTV workers, MSDs were related to measures of daily vibration exposure expressed in terms of 8-h energy-equivalent frequency-weighted acceleration magnitude [A(8)]. To calculate A(8), the acceleration magnitudes of vibration were weighted by means of four alternative frequency weightings of HTV. The associations between MSDs, individual characteristics, physical work load other than vibration, and psychological strain were also investigated. RESULTS: The occurrence of upper limb MSDs was greater in the HTV workers than in the controls. After adjustment for potential confounders, the occurrence of elbow/forearm and wrist/hand MSDs increased with the increase in vibration exposure. A measure of model selection did not reveal any substantial difference in the performance of the alternative frequency weightings of HTV for the prediction of neck and upper limb MSDs. In the study population, age, hard physical work load, and poor psychological well-being were associated with both neck and upper limb MSDs. CONCLUSIONS: In this study, there was evidence for significant exposure-response relationships between HTV exposure and MSDs in the distal sites of the upper limbs. There were no differences in the prediction of neck and upper limb MSDs between measures of daily vibration exposure calculated with alternative frequency weightings of acceleration magnitude.

Transdermal nicotine absorption handling e-cigarette refill liquids.

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 µg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 µg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 µg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids.

Relationships of low back outcomes to internal spinal load: a prospective cohort study of professional drivers.

PURPOSE: To investigate the relationships between low back symptoms and alternative measures of external dose and internal spinal dose in professional drivers exposed to whole body vibration (WBV). METHODS: The occurrence of low back symptoms was investigated in a cohort of 537 drivers over a 2-year follow-up period. Low back pain (LBP), individual characteristics, and work-related risk factors were investigated with a structured questionnaire. Exposure to WBV was evaluated by means of measures of external dose (daily vibration exposure in terms of either equivalent continuous acceleration over an 8-h period (A(8)) or vibration dose value according to the EU Directive on mechanical vibration) and measures of internal lumbar load (daily compressive dose S ed and risk factor R according to ISO/CD 2631-5 2014). RESULTS: In the drivers' cohort, the cumulative incidence of 12-month low back outcomes was 16.8% for LBP, 9.3% for chronic LBP, and 21.8% for sciatic pain. The measures of internal spinal load were better predictors of the occurrence of low back symptoms than the measures of daily vibration exposure. A twofold increase in the risk estimates for low back outcomes was found in the upper quartile of the R factor (0.41-0.72 units) compared to the lower one (0.07-0.19 units). CONCLUSIONS: In this prospective cohort study, measures of internal spinal dose performed better than measures of daily vibration exposure (external dose) for the prediction of low back outcomes in professional drivers. The ISO boundary values of the risk factor R for low and high probabilities of adverse health effects on the lumbar spine tend to underestimate the health risk in professional drivers.

Reduction in finger blood flow induced by hand-transmitted vibration: effect of hand elevation.

OBJECTIVES: This study investigated the effect of hand elevation on reductions in finger blood flow (FBF) induced by hand-transmitted vibration. METHODS: Fourteen males attended six sessions on six separate days, with a control sessions and a vibration session (125-Hz vibration at 44 ms(-2) rms) with the right hand supported at each of three elevations: 20 cm below heart level (HL), at HL, and 20 cm above HL. Finger blood flow on the left and right hand was measured every 30 s during each 25-min session comprised of five periods: (1) no force and no vibration (5 min), (2) 2-N force and no vibration (5 min), (3) 2-N force and vibration (5 min), (4) 2-N force and no vibration (5 min), and (5) no force and no vibration (5 min). RESULTS: Without vibration, FBF decreased with increasing elevation of the hand. During vibration of the right hand, FBF reduced on both hands. With elevation of the right hand, the percentage reduction in FBF due to vibration (relative to FBF on the same finger at the same elevation before exposure to vibration) was similar on the middle and little fingers of both hands. After cessation of vibration, there was delayed return of FBF with all three hand heights. CONCLUSIONS: Vibration of one hand reduces FBF on both exposed and unexposed hands, with the reduction dependent on the elevation of the hand. The mechanisms responsible for vibration-induced reductions in FBF seem to reduce blood flow as a percentage of the blood flow without vibration. Tasks requiring the elevation of the hands will be associated with lower FBF, and the FBF will be reduced further if there is exposure to hand-transmitted vibration.

Nanoparticles skin absorption: New aspects for a safety profile evaluation.

Nanoparticles (NPs) skin absorption is a wide issue, which needs to be better understood. The attempt of this review is to summarize the scientific evidence concerning open questions, i.e.: the role of NPs intrinsic characteristics (size, shape, charge, surface properties), the penetration of NPs through the intact or impaired skin barrier, the penetration pathways which should be considered and the role of NPs interaction in physiological media. The outcomes suggest that one main difference should be made between metal and non-metal NPs. Both kinds have a secondary NPs size which is given after interaction in physiological media, and allows a size-dependent skin penetration: NPs⩽4nm can penetrate and permeate intact skin, NPs size between 4 and 20nm can potentially permeate intact and damaged skin, NPs size between 21 and 45nm can penetrate and permeate only damaged skin, NPs size>45nm cannot penetrate nor permeate the skin. Other aspects play an important role, mostly for metal NPs, i.e., dissolution in physiological media, which can cause local and systemic effects, the sensitizing or toxic potential and the tendency to create aggregates. This paper suggests a decision tree to evaluate the potential risk for consumers and workers exposed to NPs.

Association between vasoconstriction during and following exposure to hand-transmitted vibration.

OBJECTIVES: This study investigated whether reductions in finger blood flow (FBF) during and after vibration are similarly dependent on the magnitude and duration of the vibration. METHODS: FBF on the left and right hand was measured every minute during, and for 1 h following, exposure of the right hand to one of three magnitudes of 125-Hz sinusoidal vibration (0, 22, or 88 ms(-2) rms) for one of two durations (7.5 or 15 min). Each of five experimental sessions was comprised of five periods: (i) no force and no vibration (5 min), (ii) 2-N force and no vibration (5 min), (iii) 2-N force and vibration (7.5 or 15 min), (iv) 2-N force and no vibration (5 min), and (v) no force and no vibration (60 min). RESULTS: Vibration reduced FBF in the exposed and unexposed hands, both during and after vibration. With increased magnitude of vibration, there was increased vasoconstriction in all fingers during and after exposure, and longer recovery times after vibration exposure. With increased duration of vibration, there were no changes in vascular responses during exposure but increased vasoconstriction after exposure and prolonged recovery times. With the greater vibration magnitude, the reduction in FBF during exposure was correlated with the time taken to recover after exposure. CONCLUSIONS: Subjects with greater reduction in blood flow during vibration exposure also have stronger and longer vasoconstriction during subsequent recovery. The correlation between vascular changes during and after vibration exposure suggests similar mechanisms control FBF during and after vibration exposure.

Slow-Paced Breathing Intervention in Healthcare Workers Affected by Long COVID: Effects on Systemic and Dysfunctional Breathing Symptoms, Manual Dexterity and HRV.

BACKGROUND: Many COVID-19 survivors still experience long-term effects of an acute infection, most often characterised by neurological, cognitive and psychiatric sequelae. The treatment of this condition is challenging, and many hypotheses have been proposed. Non-invasive vagus nerve stimulation using slow-paced breathing (SPB) could stimulate both central nervous system areas and parasympathetic autonomic pathways, leading to neuromodulation and a reduction in inflammation. The aim of the present study was to evaluate physical, cognitive, emotional symptoms, executive functions and autonomic cardiac modulation after one month of at-home slow breathing intervention. METHODS: 6655 healthcare workers (HCWs) were contacted via a company email in November 2022, of which N = 58 HCWs were enrolled as long COVID (cases) and N = 53 HCWs as controls. A baseline comparison of the two groups was performed. Subsequently each case was instructed on how to perform a resonant SPB using visual heart rate variability (HRV) biofeedback. They were then given a mobile video tutorial breathing protocol and asked to perform it three times a day (morning, early afternoon and before sleep). N = 33 cases completed the FU. At T0 and T1, each subject underwent COVID-related, psychosomatic and dysfunctional breathing questionnaires coupled with heart rate variability and manual dexterity assessments. RESULTS: After one month of home intervention, an overall improvement in long-COVID symptoms was observed: confusion/cognitive impairment, chest pain, asthenia, headache and dizziness decreased significantly, while only a small increase in manual dexterity was found, and no relevant changes in cardiac parasympathetic modulation were observed.

Heart Rate Variability Modulation Through Slow-Paced Breathing in Health Care Workers with Long COVID: A Case-Control Study.

BACKGROUND: Long COVID is a syndrome persisting 12+ weeks after COVID-19 infection, impacting life and work ability. Autonomic nervous system imbalance has been hypothesized as the cause. This study aims to investigate cardiovascular autonomic function in health care workers (HCWs) with Long COVID and the effectiveness of slow-paced breathing (SPB) on autonomic modulation. METHODS: From December 1, 2022 to March 31, 2023, 6655 HCWs of the University Hospitals of Trieste (Northeast Italy) were asked to participate in the study by company-email. Inclusion/exclusion criteria were assessed. Global health status and psychosomatic disorders were evaluated through validated questionnaires. Heart rate variability was assessed by finger-photoplethysmography during spontaneous breathing and SPB, which stimulate vagal response. Long COVID HCWs (G1) were contrasted with Never infected (G2) and Fully recovered COVID-19 workers (G3). RESULTS: There were 126 HCWs evaluated. The 58 Long COVID were assessed at a median time because COVID-19 of 419.5 days (interquartile range 269-730) and had significantly more psychosomatic symptoms and lower detectability of spontaneous systolic pressure oscillation at 0.1 Hz (Mayer wave - baroreflex arc) during spontaneous breathing compared with 53 never-infected and 14 fully-recovered HCWs (19%, 42%, and 40%, respectively, P = .027). During SPB, the increase in this parameter was close to controls (91.2%, 100%, and 100%, respectively, P = .09). No other differences in heart rate variability parameters were found among groups. CONCLUSIONS: Resting vascular modulation was reduced in Long COVID, while during SPB, baroreflex sensitivity effectively improved. Long-term studies are needed to evaluate whether multiple sessions of breathing exercises can restore basal vascular reactivity and reduce cardiovascular risk in these patients.

Effectiveness of a Skin Care Program With a Cream Containing Ceramide C and a Personalized Training for Secondary Prevention of Hand Contact Dermatitis.

Background/Objectives: The aim of our study was to investigate the effectiveness of personalized training on skin protection associated with the regular use of ceramide-containing cream (CC) versus other creams (OC) for improving hand contact dermatitis. Methods: We performed a double-center randomized trial that enrolled workers with hand dermatitis. All workers received personalized training. The intervention was 3 times per day application of the study emollient. The control arm used an emollient of choice without ceramide, as needed. The primary outcome was improvement in hand dermatitis at 1 and 3 months of follow-up. Results: In total, 102 patients with hand dermatitis were enrolled in this study. Improvement in dermatitis was found in 40%, 52.5%, 50%, and 63% of OC and CC, at the first and second follow-ups, respectively. The use of CC was significantly associated with an improvement in dermatitis (odds ratios 2.6; 95% confidence intervals 1.30-5.2), analyzed using generalized equation estimation during the follow-up. Conclusion: Our study demonstrated that an educational personalized intervention could improve the signs and symptoms in patients with hand dermatitis, and the use of a CC resulted in a significantly better outcome during the 3 months of follow-up.

Cognitive Profile Discrepancies among Typical University Students and Those with Dyslexia and Mixed-Type Learning Disorder.

BACKGROUND: Previous studies have identified areas of cognitive weakness in children diagnosed with Specific Learning Disorder (SLD), in the areas of working memory and processing speed in particular. In adulthood, this literature is still scant, and no studies have compared the cognitive profile of university students with dyslexia (DD) with that of students with Mixed-type SLD. METHOD: Thus, in this study, the WAIS-IV was used to examine the cognitive functioning of three groups of university students: students with DD, with Mixed-type SLD, and typical students. Statistical analyses were performed to examine differences in WAIS-IV FSIQ, main, and additional indexes and subtests. RESULTS: The results showed strengths in perceptual reasoning and good verbal comprehension abilities in both the DD and Mixed-type SLD group, with weaknesses in working memory and processing speed, leading to a pattern of a better General Ability Index (GAI) than Cognitive Proficiency Index (CPI) in both clinical groups. Thus, discrepancies between GAI and CPI, well documented in children with SLD, still manifest in adulthood in university students. Our findings also revealed worse cognitive performance in university students with mixed learning disorder relative to students with only a reading deficit. CONCLUSIONS: The cognitive features and distinctive subtest profiles that emerged should guide the assessment and the definitions of intervention programs, special educational needs, and strategies of compensation.

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.