Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies that activate platelets through FcγRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications.

Oxidative Damage and Post-COVID Syndrome: A Cross-Sectional Study in a Cohort of Italian Workers.

In addition to the acute symptoms after infection, patients and society are also being challenged by the long-term effects of COVID-19, known as long COVID. Oxidative stress, as a pivotal point in the pathophysiology of COVID-19, could potentially be also involved in the development of the post-COVID syndrome. The aim of the present study was to evaluate the relationship between changes in oxidative status and the persistence of long-COVID symptoms in workers with a previous mild COVID-19 infection. A cross-sectional study was conducted among 127 employees of an Italian university (80 with a previous COVID-19 infection, and 47 healthy subjects). The TBARS assay was used to detect malondialdehyde serum levels (MDA), while total hydroperoxide (TH) production was measured by a d-ROMs kit. A significant difference in mean serum MDA values was found between previously infected subjects and healthy controls and (4.9 µm vs. 2.8 µm, respectively). Receiver-operating characteristic (ROC) curves showed high specificity and good sensibility (78.7% and 67.5%, respectively) for MDA serum levels. A random forest classifier identified the hematocrit value, MDA serum levels, and IgG titer against SARS-CoV-2 as features with the highest predictive value in distinguishing 34 long-COVID from 46 asymptomatic post-COVID subjects. Oxidative damage persists in subjects with previous COVID-19 infection, suggesting a possible role of oxidative stress mediators in the pathogenesis of long COVID.

Detection of Endosymbiont Candidatus Midichloria mitochondrii and Tickborne Pathogens in Humans Exposed to Tick Bites, Italy.

During 2021, we collected blood and serum samples from 135 persons exposed to tick bites in southern Italy. We serologically and molecularly screened for zoonotic tickborne pathogens and only molecularly screened for Candidatus Midichloria mitochondrii. Overall, 62 (45.9%) persons tested positive for tickborne pathogens. Coxiella burnetii was detected most frequently (27.4%), along with Rickettsia spp. (21.5%) and Borrelia spp. (10.4%). We detected Candidatus M. mitochondrii DNA in 46 (34.1%) participants who had statistically significant associations to tickborne pathogens (p<0.0001). Phylogenetic analysis of Candidatus M. mitochondrii sequences revealed 5 clades and 8 human sequence types that correlated with vertebrates, Ixodes spp. ticks, and countries in Europe. These data demonstrated a high circulation of tickborne pathogens and Candidatus M. mitochondrii DNA in persons participating in outdoor activities in southern Italy. Our study shows how coordinated surveillance among patients, clinicians, and veterinarians could inform a One Health approach for monitoring and controlling the circulation of tickborne pathogens.

COVID19 outbreak in Lombardy, Italy: An analysis on the short-term relationship between air pollution, climatic factors and the susceptibility to SARS-CoV-2 infection.

Short-term exposure to air pollution, as well as to climate variables have been linked to a higher incidence of respiratory viral diseases. The study aims to assess the short-term influence of air pollution and climate on COVID19 incidence in Lombardy (Italy), during the early stage of the outbreak, before the implementation of the lockdown measures. The daily number of COVID19 cases in Lombardy from February 25th to March 10th, 2020, and the daily average concentrations up to 15 days before the study period of particulate matter (PM10, PM2.5), O3, SO2, and NO2 together with climate variables (temperature, relative humidity - RH%, wind speed, precipitation), were analyzed. A univariable mixed model with a logarithm transformation as link function was applied for each day, from 15 days (lag15) to one day (lag1) before the day of detected cases, to evaluate the effect of each variable. Additionally, change points (Break Points-BP) in the relationship between incident cases and air pollution or climatic factors were estimated. The results did not show a univocal relationship between air quality or climate factors and COVID19 incidence. PM10, PM2.5 and O3 concentrations in the last lags seem to be related to an increased COVID19 incidence, probably due to an increased susceptibility of the host. In addition, low temperature and low wind speed in some lags resulted associated with increased daily COVID19 incidence. The findings observed suggest that these factors, in particular conditions and lags, may increase individual susceptibility to the development of viral infections such as SARS-CoV-2.

Clinical and radiological criteria for the differential diagnosis between asbestosis and idiopathic pulmonary fibrosis: Application in two cases.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) and asbestosis are pulmonary interstitial diseases that may present overlapping clinical aspects in the full-blown phase of the disease. For both clinical entities the gold standard for diagnosis is histological examination, but its execution poses ethical problems, especially when performed for preventive or forensic purposes. OBJECTIVE: To evaluate the application of internationally accepted clinical, anamnestic and radiological criteria for differential diagnosis between asbestosis and IPF, and to assess the ability to discriminate between the two diseases. Even if clinically similar, the two diseases present extremely different prognostic and therapeutic perspectives. METHODS: Two clinical cases of IPF are reported, in which the differential diagnosis was made by studying occupational exposure to asbestos, the onset and progression of clinical symptoms, and the identification of specific radiological elements by means of chest High Resolution Computed Tomography (HRCT). RESULTS: The diagnosis of IPF could be made on the basis of the absence of significant exposure to asbestos, the early onset and rapid progression of dyspnea and restrictive ventilatory defects, in association with a pulmonary radiological pattern characterized by peculiar elements such as honeycombing. DISCUSSION: The diagnostic procedure adopted to make a differential diagnosis with asbestosis provides practical clinical elements facilitating the differentiation between the two forms of pulmonary fibrosis, a fundamental aspect of the activity of the occupational physician.

Occupational exposure to carbon fibers impregnated with epoxy resins and evaluation of their respirability.

Objectives: The study aims to investigate occupational exposure to carbon fibers impregnated with epoxy resins (carbon fiber reinforced [CFR]) in workers at an airplane fuselage section construction plant, by environmental and biological monitoring.Materials and methods: Determination of airborne CFR was done by environmental sampling with active samplers, 11 of which were stationary and 19 personal samplings. The subsequent analyses were performed in the scanning electron microscope fitted with an X-ray microanalysis system (SEM-EDXA). Biological monitoring was carried out by determining CFR in exhaled breath condensate (EBC) collected from 19 male workers who wore personal environmental samplers (exposed workers) and from 10 male workers at the same factory who had no occupational exposure to CFR (internal controls). CFR analysis was done by SEM, applying the method used for determining asbestos fibers in aqueous samples.Results: The airborne CFR concentrations were found to be significantly higher (p = 0.03) at personal samplings (median value 7.01 ff/L, range 1.24-11.16 ff/L) than stationary samplings (median value 1.93 ff/L, range 0.55-10.09 ff/L). The aerodynamic diameters calculated starting from the length and geometric diameter of the sampled CFRs were always higher than 20 µm. CFR was not found in any of the EBC samples collected from the exposed workers and controls.Conclusions: Despite the evidence of occupational exposure to low concentrations of CFR, the absence of such fibers in the EBC in the exposed workers confirms their non-respirability, as expected based on their aerodynamic diameter.

Women and men, authors and victims of workplace bullying in Italy: a literature review.

INTRODUCTION: It is known in literature that women are frequently victims of murder, sexual assault and stalking. It is interesting to investigate the gender characterization when workplace bullying occurs. OBJECTIVES: To investigate the phenomenon of workplace bullying and to understand if there are any relevant data about the gender aspects of workplace bullying by reviewing the literature in Italy. METHODS: Review of articles on a sample of Italian workers. The research question followed the P.E.C.O. model and the article selection is based on PRISMA statement. Fourteen research strings were applied on: Pubmed, Microsoft Academic e Science Direct. A total of 32 articles were selected. RESULTS: There are few studies in which gender differences on workplace bullying and crimes related are analysed, in some cases it is considered in the research but not in the results section (n=6 articles). In the studies selected women are predominantly victims (n=10 articles), the aggressors instead are usually men (n=2 articles). The attacks suffered by women are frequently discriminations due to family management, children and gender related issues (n=6 articles). Men have the major consequences on mental health if compared to women (n=7 articles). CONCLUSIONS: Gender is relevant in the characterization of workplace bullying. There is a need for further investigation focusing on gender differences between perpetrators and victims of workplace bullying offences. A unique evaluation protocol is necessary for evaluating workplace bullying, the crimes linked to it and gender differences, to obtain a more accurate comparability of data.

Neurofilament light chain and glial fibrillary acid protein levels are elevated in post-mild COVID-19 or asymptomatic SARS-CoV-2 cases.

Given the huge impact of the COVID-19 pandemic, it appears of paramount importance to assess the cognitive effects on the population returning to work after COVID-19 resolution. Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) represent promising biomarkers of neuro-axonal damage and astrocytic activation. In this cohort study, we explored the association between sNfL and sGFAP concentrations and cognitive performance in a group of 147 adult workers with a previous asymptomatic SARS-CoV-2 infection or mild COVID-19, one week and, in 49 of them, ten months after SARS-Cov2 negativization and compared them to a group of 82 age and BMI-matched healthy controls (HCs). sNfL and sGFAP concentrations were assessed using SimoaTM assay Neurology 2-Plex B Kit. COVID-19 patients were interviewed one-on-one by trained physicians and had to complete a list of questionnaires, including the Cognitive Failure Questionnaire (CFQ). At the first assessment (T0), sNfL and sGFAP levels were significantly higher in COVID-19 patients than in HCs (p < 0.001 for both). The eleven COVID-19 patients with cognitive impairment had significantly higher levels of sNfL and sGFAP than the others (p = 0.005 for both). At the subsequent follow-up (T1), sNfL and sGFAP levels showed a significant decrease (median sNfL 18.3 pg/mL; median sGFAP 77.2 pg/mL), although they were still higher than HCs (median sNfL 7.2 pg/mL, median sGFAP 63.5 pg/mL). Our results suggest an ongoing damage involving neurons and astrocytes after SARS-Cov2 negativization, which reduce after ten months even if still evident compared to HCs.

West Nile Virus Infection in Occupational Settings-A Systematic Review.

BACKGROUND: West Nile virus (WNV) is an emerging mosquito-borne neurotropic virus, belonging to the Flaviviridae family and the Orthoflavivirus genus. The effective control of WNV requires a targeted preventive strategy that also needs the identification of the higher-risk populations. Hence, this study focused on a systematic literature review of WNV-acquired infection in work-related settings and the assessment of the exposure risks among different occupational categories. METHODS: A comprehensive search was conducted to identify studies until September 2023 in multiple databases such as PubMed/MEDLINE, SCOPUS and Web of Science, according to the PRISMA 2020 statement. Risk of bias of collected papers was assessed by the ROB tool of the National Toxicology Program's Office of Health Assessment and Translation handbook. RESULTS: A total of 21 studies were included in the systematic review, out of which seventeen were observational studies and four were case reports. Workers identified as at higher risk for WNV infection were military workers, veterinarians, agricultural workers, farmers, and laboratory workers with contact with infected fluids or aerosols. CONCLUSIONS: The identification of higher-risk workers could facilitate active surveillance by occupational physicians, which could improve our understanding of the epidemiology of WNV and, in addition, could help tailor appropriate preventive recommendations, reducing the overall burden of disease in high-risk areas.

Repurposing antiviral drugs against HTLV-1 protease by molecular docking and molecular dynamics simulation.

Human T-cell leukemia virus type I (HTLV-1) belongs to the delta retrovirus family and the etiological agent of adult T-cell leukemia (ATL(. While the current HTLV-1 therapy, relies on using Zidovudine plus IFN-γ, there is no FDA approved drugs against it. In silico drug repurposing is a fast and accurate way for screening US-FDA approved drugs to find a therapeutic option for the HTLV-1 infection. So that, this research aims to analyze a dataset of approved antiviral drugs as a potential prospect for an anti-viral drug against HTLV-1 infection. Molecular docking simulation was performed to identify interactions of the antiviral drugs with the key residues in the HTLV-1 protease binding site. Then, molecular dynamics simulation was also performed for the potential protein-ligand complexes to confirm the stable behavior of the ligands inside the binding pocket. The best docking scores with the target was found to be Simeprevir, Atazanavir, and Saquinavir compounds which indicate that these drugs can firmly bind to the HTLV-1 protease. The MD simulation confirmed the stability of Simeprevir-protease, Atazanavir-Protease, and Saquinavir-Protease interactions. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against HTLV-1 infection.Communicated by Ramaswamy H. Sarma.

Recombinant GPEHT Fusion Protein Derived from HTLV-1 Proteins with Alum Adjuvant Induces a High Immune Response in Mice.

The human T-cell leukemia virus type 1 (HTLV-1) is a positive single-stranded RNA virus that belongs to the delta retrovirus family. As a result, a vaccine candidate that can be recognized by B cells and T cells is a good candidate for generating a durable immune response. Further, the GPEHT protein is a multi-epitope protein designed based on the Gag, Pol, Env, Hbz, and Tax proteins of HTLV-1. In developing a suitable and effective vaccine against HTLV-1, the selection of a designed protein (GPEHT) with the formulation of an alum adjuvant was conducted. In this study, we assessed the potential of a multi-epitope vaccine candidate for stimulating the immune response against HTLV-1. In assessing the type of stimulated immune reaction, total IgG, IgG1, and IgG2a isotypes, as well as the cytokines associated with Th1 (IFN-γ), Th2 (IL-4), and Th17 (IL-17), were analyzed. The outcomes showed that the particular antisera (total IgG) were more elevated in mice that received the GPEHT protein with the alum adjuvant than those in the PBS+Alum control. A subcutaneous vaccination with our chimera protein promoted high levels of IgG1 and IgG2a isotypes. Additionally, IFN-γ, IL-4, and IL-17 levels were significantly increased after spleen cell stimulation in mice that received the GPEHT protein. The immunogenic analyses revealed that the GPEHT vaccine candidate could generate humoral and cell-mediated immune reactions. Ultimately, this study suggests that GPEHT proteins developed with an alum adjuvant can soon be considered as a prospective vaccine to more accurately evaluate their protective efficacy against HTLV-1.

Evaluation of the dual effects of antiviral drugs on SARS-CoV-2 receptors and the ACE2 receptor using structure-based virtual screening and molecular dynamics simulation.

The use of US FDA-approved drugs is preferred due to the need for lower costs and less time. In in silico medicine, repurposing is a quick and accurate way to screen US FDA-approved medications to find a therapeutic option for COVID-19 infection. Dual inhibitors possess dual inhibitory activity, which may be due to the inhibition of two different enzymes, and are considered better than combination therapy from the developmental and clinical perspectives. In this study, a molecular docking simulation was performed to identify the interactions of antiviral drugs with the critical residues in the binding site of the main SARS-CoV-2 protease, spike glycoprotein, and papain-like protease receptors compared to the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor of host cells. Each of the receptors was docked with 70 US FDA-approved antiviral drugs using AutoDock Vina. A molecular dynamics (MD) simulation study was also used for 100 ns to confirm the stability behaviour of the ligand receptor complexes. Among the drugs that had the strongest interaction with the SARS-CoV-2 main protease, spike glycoprotein and papain-like protease receptors, and host cell ACE2 receptors, Simeprevir, Maraviroc and Saquinavir had dual inhibitory effects. The MD simulation study confirmed the stability of the strongest interactions between the antiviral drugs and the main protease, ACE2, spike glycoprotein, and papain-like protease receptors to 100 ns. However the results of MMPBSA analysis showed that the bond between Saquinavir and the ACE2 receptor was weak. Simeprevir and Maraviroc drugs had acceptable binding energies with dual receptors, especially the Simeprevir.Communicated by Ramaswamy H. Sarma.

Seroprevalence of Leishmania infantum in outdoor workers from southern Italian endemic regions.

Visceral leishmaniasis is a zoonotic vector-borne disease caused by Leishmania infantum. The infection often remains asymptomatic, though clinical forms may occur in immunosuppressed individuals. Although data on leishmaniasis in humans are available worldwide, the exposure to L. infantum of workers conducting outdoor activities has been scantly investigated, and it is limited to military personnel operating in endemic regions. This study aimed to assess the seroprevalence of L. infantum in different groups of outdoor workers and the occupational risk factors. The cross-sectional study was performed on 229 workers including forestry guards, farmers, veterinarians, geologists and agronomists from three regions of southern Italy (i.e., Apulia, Basilicata and Campania). All serum samples were screened for L. infantum-specific IgG/IgM by using automated indirect chemiluminescent immunoassays. Overall, 5.7% (13/229) of workers was positive to anti-L. infantum antibodies, with the highest seroprevalence in veterinarians (13.6%). An increased occupational health surveillance for L. infantum infection in outdoor workers is essential to better understand the risk of exposure in specific jobs. Furthermore, guidelines and education along with a One Health collaboration among veterinarians, physicians, parasitologists and occupational health care professionals are crucial for the prevention of this disease.

SARS-CoV-2 Infections, Re-Infections and Clinical Characteristics: A Two-Year Retrospective Study in a Large University Hospital Cohort of Vaccinated Healthcare Workers.

At the University Hospital of Bari, during the first year after the start of the mandatory vaccination campaign with BNT162b2 mRNA COVID-19 vaccine, the preliminary results of an observational study showed a significant prevalence of SARS-CoV-2 breakthrough infections (BIs) among healthcare workers (HCWs), but no hospitalization or deaths. In the present study, we extended the observation period (January 2021-January 2023) with the aim of determining the incidence, characteristics and clinical course of SARS-CoV-2 BIs among 6213 HCWs. All HCWs were regularly monitored and screened. To allow return to work after BI, the protocol required one negative nasopharyngeal swab test followed by a medical examination certifying complete clinical recovery. We observed an overall incidence rate of SARS-CoV-2 BIs of 20.2%. Females were most affected, especially in the nurse group compared with doctors and other HCWs (p < 0.0001). Cardiovascular diseases were the most frequent comorbidity (n = 140; 11.4%). The source of infection was non-occupational in 52.4% of cases. Most cases (96.9%) showed minor symptoms and only two cases of hospitalization (one in intensive care unit), 13 cases of re-infection and no deaths were recorded. Our results confirm that SARS-CoV-2 infection can break vaccination protection but the clinical course is favorable.

Evaluation of immune response to SARS-CoV-2 Omicron sublineages six months after different vaccination regimens in Italy.

The Omicron variant is the most divergent, displaying more mutations than previous SARS-CoV-2 variants, particularly in the gene that encodes the spike protein. This study aimed to assess the persistence of neutralizing antibodies towards the SARS-CoV-2 Omicron sublineages (BA.2, BA.5, BQ.1, XBB and XBB1.5) six months after the third dose in different vaccination regimens. Subjects who received 3 doses of mRNA vaccine retained their neutralization activity against BA.2 and BA.5, even though 56.3% and 66.7% showed a ≥ 2-fold reduction in the neutralizing antibody titre, respectively. Subjects who had received the adenovirus-based vaccine plus a booster dose of mRNA vaccine retained their neutralization activity especially against BA.2. With regard to BQ.1, XBB and XBB.1.5, the majority of the subjects showed a ≥ 2-fold reduction in neutralizing antibody titre, with the greatest evasion being observed in the case of XBB. Overall, our results provide further evidence that triple homologous/heterologous vaccination and hybrid immunity result in detectable neutralizing antibodies against the ancestral virus; however, emerging Omicron sublineages, such as XBB and XBB.1.5, show a great evasive capacity, which compromises the effectiveness of current COVID-19 vaccines.

Impact of COVID-19 emergency on the psychological well-being of susceptible individuals.

The current pandemic has exerted an unprecedented psychological impact on the world population, and its effects on mental health are a growing concern. The present study aims to evaluate psychological well-being (PWB) during the COVID-19 crisis in university workers with one or more diseases likely to increase the risk of severe outcomes in the event of SARS-CoV-2 infection, defined as susceptible. 210 susceptible employees of an Italian University (aged 25-71 years) were recruited during the COVID-19 second wave (October-December 2020). A group comprising 90 healthy university employees (aged 26-69 years) was also recruited. The self-report Psychological General Well Being Index (PGWBI) was used to assess global PWB and the influence on six sub-domains: anxiety, depressed mood, positive well-being, self-control, general health, and vitality. We applied non-linear dimension-reduction techniques and regression methods to 45 variables in order to assess the main demographic, occupational, and general-health-related factors predicting PWB during the COVID-19 crisis. PGWBI score was higher in susceptible than in healthy workers, both as total score (mean 77.8 vs 71.3) and across almost all subscales. Age and jobs involving high social interaction before the pandemic were inversely associated with the PWB total score, general health, and self-control subscores. The current data suggest no decline in PWB during the second wave of COVID-19 health emergency in susceptible individuals of working age. Critically, higher risk for mental-health issues appears to be inversely related to age, particularly among individuals deprived of their previous level of social interaction at work.