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A neurogenic pathway, involving airway TRPV-1, has been implicated in acute cardiovascular events occurring after peaks of air pollution. We tested whether inhaled prostaglandin-E 2 (PGE 2 ) and bradykinin (BK) regulate TRPV-1 activity in vivo by changing cough response to capsaicin (CPS) and affecting heart rate variability (HRV), while also taking into account the influence of TRPV-1 polymorphisms (SNPs). Moreover, we assessed the molecular mechanism of TRPV-1 modulation in vitro. Seventeen healthy volunteers inhaled 100 μg PGE 2 , 200 μg BK or diluent in a randomized double-blind fashion. Subsequently, the response to CPS was assessed by cough challenge and the sympathetic activity by HRV, expressed by low (nLF) and high (nHF) normalized frequency components, as well as nLF/nHF ratio. Intracellular [Ca 2+ ] was measured in HeLa cells, transfected with wild-type TRPV-1, pre-treated with increasing doses of PGE 2 , BK or diesel exhaust particulate (DEP), after CPS stimulation. Six functional TRPV-1 SNPs were characterized in DNA from each subject. Inhalation of PGE 2 and BK was associated with significant increases in cough response induced by 30 μM of CPS (cough number after PGE 2  = 4.20 ± 0.42; p  < 0.001, and after BK = 3.64 ± 0.37; p  < 0.01), compared to diluent (2.77 ± 0.29) and in sympathetic activity (nLF/nHF ratio after PGE 2  = 6.1; p  < 0.01, and after BK = 4.2; p  < 0.05), compared to diluent (2.5–3.3). No influence of SNPs was observed on autonomic regulation and cough sensitivity. Unlike PGE 2 and BK, DEP directly activated TRPV-1. Inhalation of PGE 2 and BK sensitizes TRPV-1 and is associated with autonomic dysregulation of cardiac rhythm in healthy subjects.

The battle against the new coronavirus that continues to kill millions of people will be still long. Novel strategies are demanded to control infection, mitigate symptoms and treatment of COVID-19. This is even more imperative given the long sequels that the disease has on the health of the infected. The discovery that S protein includes two ankyrin binding motifs (S-ARBMs) and that the transient receptor potential vanilloid subtype 1 (TRPV-1) cation channels contain these ankyrin repeat domains (TRPs-ARDs) suggest that TRPV-1, the most studied member of the TRPV channel family, can play a role in binding SARS-CoV-2. This hypothesis is strengthened by studies showing that other respiratory viruses bind the TRPV-1 on sensory nerves and epithelial cells in the airways. Furthermore, the pathophysiology in COVID-19 patients is similar to the effects generated by TRPV-1 stimulation. Lastly, treatment with agonists that down-regulate or inactivate TRPV-1 can have a beneficial action on impaired lung functions and clearance of infection. In this review, we explore the role of the TRPV-1 channel in the infection, susceptibility, pathogenesis, and treatment of COVID-19, with the aim of looking at novel strategies to control infection and mitigate symptoms, and trying to translate this knowledge into new preventive and therapeutic interventions.

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.

Background The prevalence of obesity is increasing all over the world, resulting in a global health emergency. The impact of obesity on the risk of SARS-CoV-2 infection and symptom severity, especially among high-risk working populations such as health workers, deserves further studies. Methods A multicentric retrospective cohort study was conducted among health workers at four Italian University Hospitals belonging to the ORCHESTRA Project. Data were collected through an online survey, investigating sociodemographic and clinical data, until September 2022. Results The questionnaire was filled out by 5777 health workers. The median age was 46 years old (I–III quartile 20–72) and 75.5% were females. Data on BMI was available for 5470 participants. Overweight and obese subjects amounted to 23.4% and 9.8%, respectively. Naïve health workers were the majority (57.4%). Overweight and obese subjects were at a higher risk of infection only before vaccination with respect to normoweight subjects (RRR = 1.28 (IC 95% 1.01–1.62, p = 0.039) and 1.36 (1.00–1.86, p = 0.047), respectively). Major acute and post-acute COVID-19 symptoms were more common among obese subjects, as compared to those with a normal weight (35.2% vs. 23.5%, and 14.2% vs. 9.3%). BMI did not reduce antibody levels after vaccination. On the contrary, overweight and obese health workers had a significantly higher RGM after the third dose (1.12 and 1.48, respectively; normal weight as reference). Conclusions Overweight and obese subjects are at a higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 vaccination fosters a high antibody response even in these individuals. Vaccination against SARS-CoV-2 should be prioritized in subjects with a high BMI, especially in highly exposed workers, such as health workers.

Aging is the predominant risk factor for most degenerative diseases, including chronic obstructive pulmonary disease (COPD). This process is however very heterogeneous. Defining the biological aging of individual tissues may contribute to better assess this risky process. In this study, we examined the biological age of induced sputum (IS) cells, and peripheral blood leukocytes in the same subject, and compared these to assess whether biological aging of blood leukocytes mirrors that of IS cells. Biological aging was assessed in 18 COPD patients (72.4 ± 7.7 years; 50% males). We explored mitotic and non-mitotic aging pathways, using telomere length (TL) and DNA methylation-based age prediction (DNAmAge) and age acceleration (AgeAcc) (i.e., difference between DNAmAge and chronological age). Data on demographics, life style and occupational exposure, lung function, and clinical and blood parameters were collected. DNAmAge (67.4 ± 5.80 vs. 61.6 ± 5.40 years; p = 0.0003), AgeAcc (−4.5 ± 5.02 vs. −10.8 ± 3.50 years; p = 0.0003), and TL attrition (1.05 ± 0.35 vs. 1.48 ± 0.21 T/S; p = 0.0341) are higher in IS cells than in blood leukocytes in the same patients. Blood leukocytes DNAmAge ( r = 0.927245; p = 0.0026) and AgeAcc ( r = 0.916445; p = 0.0037), but not TL, highly correlate with that of IS cells. Multiple regression analysis shows that both blood leukocytes DNAmAge and AgeAcc decrease (i.e., younger) in patients with FEV 1 % enhancement ( p = 0.0254 and p = 0.0296) and combined inhaled corticosteroid (ICS) therapy ( p = 0.0494 and p = 0.0553). In conclusion, new findings from our work reveal a differential aging in the context of COPD, by a direct quantitative comparison of cell aging in the airway with that in the more accessible peripheral blood leukocytes, providing additional knowledge which could offer a potential translation into the disease management.

Background/Objectives: This retrospective multicenter study, conducted within the ORCHESTRA Project, investigated SARS-CoV-2 reinfections among 5777 healthcare workers (HCWs) from four University Hospitals (Modena, Verona, Padova and Trieste) in northern Italy, aiming to assess the risk of reinfection and its determinants, comparing the clinical characteristics of reinfections with those of first infections, and examining the impact of preventive measures and vaccination strategies. Methods: HCWs completed an online questionnaire between June and August 2022. The survey collected demographic, occupational, and clinical data, including information on first infections and reinfections. Statistical analyses were performed using SPSS 28.0, through bivariate and multivariate approaches. Results: Response rates were 41.8% for Modena, 39.5% for Verona, 17.9% for Padova, and 17.4% for Trieste. Among the respondents, 4.8% (n = 276) experienced 2 infections and 0.5% (n = 27) reported 3 infections, out of a total of 330 reinfection cases. Additionally, 43.0% (n = 2787) reported only one infection, while 51.5% were never infected. Reinfection rates increased across five study phases (based on the epidemiological context), likely due to the emergence of new SARS-CoV-2 variants. A booster vaccine dose significantly reduced reinfection risk. Higher reinfection risk was found among HCWs aged ≤30 years, those with chronic respiratory diseases, and those working in COVID-19 wards, particularly nurses and allied health professionals. Reinfections were associated with a lower frequency of symptoms both during the period of swab positivity and after a negative swab, as well as with a shorter duration of swab positivity. No significant differences in symptom duration were found between first infections and reinfections. Conclusions: Despite its limitations, the online questionnaire proved a useful tool. Natural infection and vaccination reduced both reinfection risk and symptom severity. Prior infections should be considered in planning vaccination schedules and prioritizing HCWs.

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.

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.

ObjectivesThe aim of this study was to assess the predictors of a favourable prognosis of occupational asthma (OA) and the employment status of patients with OA at least 2 years after diagnosis.MethodsWe collected data from 204 patients who had a diagnosis of OA confirmed by a positive specific inhalation challenge. We defined OA remission as meeting the following three criteria: no asthma symptoms, no antiasthma therapy for the last year and having normal lung function at the end of follow-up. A logistic regression analysis was performed to estimate the effects of the covariates.ResultsAt 10.6±7.8-year follow-up, 60 of 204 possible patients participated in the study, and among them 17 showed OA remission. When compared with the 43 patients with persistent OA, these patients exhibited at diagnosis younger age (p=0.0039), shorter duration of symptomatic exposure (p=0.0512), better lung function expressed by higher forced vital capacity (FVC%) predicted (p=0.0164), forced expiratory volume in 1 s (FEV1) % predicted (p=0.0066) and FEV1/FVC% (p=0.0132), and less bronchial hyper-responsiveness (p=0.0118). Nevertheless, in the multivariable model, no variables were significantly associated with OA remission. At follow-up, three individuals have retired; among the remaining 57 workers, 91.2% were still employed and 43.8% of them had continued working in the same factory after ceasing exposure to the causative agent.ConclusionsThis monocentric study did not identify a strong predictor of OA remission, but documented a high employment rate and a good job preservation over a long timeframe after diagnosis of OA mainly induced by low molecular weight agents.