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The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

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Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection because of their occupational exposure. Moreover, they can be a vehicle for the virus transmission among patients. The vaccination of healthcare personnel against COVID-19 is crucial in fighting the spread of SARS-CoV-2 infection, together with strict sanitary procedures that aim to limit the risk of contagion. Unfortunately, even if COVID-19 vaccination has been proved one of the most effective tools for protecting against COVID-19, many healthcare professionals are not yet vaccinated. The aim of the current review is to contribute to identifying an effective strategy for COVID-19 prevention especially among non-vaccinated HCWs. In this review, we collected the most recent and relevant findings from literature on the protection of unvaccinated HCWs, identifying three types of measures as principal actions to protect those operators: addressing vaccine hesitancy, improving non-pharmaceutical interventions and promoting actions at personal level (respiratory hygiene, hand hygiene and use of PPE). All these interventions are very effective in preventing contagion, if well respected and conducted; nevertheless, it is essential to promote vaccination, as it is the most effective measure.

The study of developmental effect of xenobiotics in humans is limited and often relies on epidemiological data. Whether and to which extent potentially toxic compounds may cross the placental barrier, and whether adverse effects on embryo development are the consequence of direct or indirect placental-mediated action is debated. The availability of in vitro models simulating the feto-maternal interface could contribute to elucidate this issue. Here, we report the development of a novel in vitro model using murine blastocyst derived trophoblast stem cells (TSC) to mimic the placental barrier and mouse embryoid bodies (EBs) to represent the embryonic tissues. We demonstrate that this model can be used for translocation studies, as well as embryotoxicity assessment of titanium dioxide nanoparticles (TiO

Healthcare workers (HCWs) have an increased risk to be exposed to infectious diseases compared to the general population. For this reason, according to the National Immunization and Prevention Plan, all HCWs should have demonstrable evidence of immunity to measles, mumps, rubella, varicella and Hepatitis B. Earlier studies have already shown that a large percentage of Italian operators lacked immune protection for one or more of those pathogens. The aim of this study was to evaluate the immunization status for vaccine-preventable diseases of HCWs in a large Italian teaching hospital. We retrospectively evaluated clinical records and serological data of HCWs who followed the occupational health surveillance program between January 1 and December 31 2019. We reviewed the clinical records of 1,017 HCWs: 393 males and 624 females with a median age of 35.69 y (range: 19–67). Protective IgG antibody values were documented in the 88.0%, 75.7%, 90.3%, 87.4% and 85.7% of the HCWs screened, respectively, against measles, mumps, rubella, varicella and Hepatitis B. Age was significantly related to serological protection against measles, mumps and varicella but was not significantly related to protective IgG levels for rubella and HBV. Female gender was significantly related to a higher protection rate against Hepatitis B (87.8 vs 82.4%; p

COVID-19 vaccination with mRNA vaccines induces immune responses capable of neutralizing SARS-CoV-2. Commercially available serological anti-SARS-CoV-2 quantitative and neutralizing assays are essential for the determination of immune responses to vaccines. Nevertheless, at present there is a lack of validated tests to assess the mucosal response to COVID-19 vaccination and standardized analytic and pre-analytic methods have not yet been defined. The aim of our study was to evaluate the accuracy of two diagnostic immunoassays for COVID-19 (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD) on serum, saliva, and nasal secretions, by the enrollment of three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection). In order to obtain an appropriate cut-off value for the biological matrices studied, ROC curve analyses were performed. Data demonstrate that the analytical and pre-analytical method we have developed can provide accurate and reliable results for the detection of anti-SARS-CoV-2 mucosal specific antibodies (IgA-S1 and IgG-RBD) on saliva and, as a novelty, on nasal secretions, either after COVID-19 infection or in vaccinated subjects.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact on health services; hundreds of thousands of healthcare workers (HCWs) have died from coronavirus disease 2019 (COVID-19). The introduction of the BNT162b2 mRNA vaccine in Italy provided recipients with significant protection against COVID-19 within one to two weeks after the administration of the second of the two recommended doses. While the vaccine induces a robust T cell response, the protective role of factors and pathways other than those related to memory B cell responses to specific SARS-CoV-2 antigens remains unclear. This retrospective study aimed to evaluate the determinants of serological protection in a group of vaccinated HCWs (n = 793) by evaluating circulating levels of antiviral spike receptor-binding domain (S-RBD) antibodies during the nine-month period following vaccination. We found that 99.5% of the HCWs who received the two doses of the BNT162b2 vaccine developed protective antibodies that were maintained at detectable levels for as long as 250 days after the second dose of the vaccine. Multivariate analysis was performed on anti-S-RBD titers in a subgroup of participants (n = 173) that were evaluated twice during this period. The results of this analysis reveal that the antibody titer observed at the second time point was significantly related to the magnitude of the primary response, the time that had elapsed between the first and the second evaluation, and a previous history of SARS-CoV-2 infection. Of importance is the finding that despite waning antibody titers following vaccination, none of the study participants contracted severe COVID-19 during the observational period.

The COVID-19 pandemic has led to health, social and economic consequences for public health systems. As a result, the development of safe and effective vaccines, in order to contain the infection quickly became a priority. The first vaccine approved by the Italian Agency for Drugs Authorization (AIFA) was the BNT162b2 mRNA vaccine, developed by BioNTech and Pfizer (Comirnaty). Comirnaty contains a molecule called messenger RNA (mRNA), which is a nucleoside-modified RNA that encodes the SARS-CoV-2 spike glycoprotein. Even if data from phase I suggest that vaccine induced antibodies can persist for up to six months following the second shot of BNT vaccine, data regarding the real duration of immunological protection are lacking. In this study, we aimed to evaluate the duration of serological protection by detecting the presence of anti-S-RBD (receptor-binding domain) antibodies for SARS-CoV-2 among a large group of healthcare workers (HCWs) three months after vaccination. 99% of HCWs had a detectable titre of anti-S SARS-CoV-2 antibodies 90 days after the second vaccine shot. Elderly operators showed significantly lower levels of protective antibodies when compared to the younger ones, thus they could become unprotected earlier than other operators.

Lactoferrin (Lf) is a cationic glycoprotein synthetized by exocrine glands and is present in all human secretions. It is also secreted by neutrophils in infection and inflammation sites. This glycoprotein possesses antimicrobial activity due to its capability to chelate two ferric ions per molecule, as well as to interact with bacterial and viral anionic surface components. The cationic features of Lf bind to cells, protecting the host from bacterial and viral injuries. Its anti-inflammatory activity is mediated by the ability to enter inside the nucleus of host cells, thus inhibiting the synthesis of proinflammatory cytokine genes. In particular, Lf down-regulates the synthesis of IL-6, which is involved in iron homeostasis disorders and leads to intracellular iron overload, favoring viral replication and infection. The well-known antiviral activity of Lf has been demonstrated against DNA, RNA, and enveloped and naked viruses and, therefore, Lf could be efficient in counteracting also SARS-CoV-2 infection. For this purpose, we performed in vitro assays, proving that Lf exerts an antiviral activity against SARS-COV-2 through direct attachment to both SARS-CoV-2 and cell surface components. This activity varied according to concentration (100/500 μg/ml), multiplicity of infection (0.1/0.01), and cell type (Vero E6/Caco-2 cells). Interestingly, the in silico results strongly supported the hypothesis of a direct recognition between Lf and the spike S glycoprotein, which can thus hinder viral entry into the cells. These in vitro observations led us to speculate a potential supplementary role of Lf in the management of COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than one hundred million people since the beginning of the worldwide pandemic. In this study, data from a large hospital in central Italy was used to evaluate the impact of the first dose of the BNT162b2 mRNA vaccine on SARS-CoV-2 infections in terms of the prevalence of symptomatic cases, symptom duration, and viral clearance timing. All vaccinated Healthcare Workers (HCWs) with positive RT-PCR by nasopharyngeal (NP) swabs were divided into two cohorts (positive RT-PCR within day 12 and positive RT-PCR between day 13 and day 21 after first dose administration) and compared for the presence and duration of symptoms and the timing of viral clearance. The same variables were evaluated across HCWs with positive RT-PCR within 6 days after first dose administration and non-vaccinated HCWs with positive RT-PCR between 1 October 2020 and 28 February 2021. Eighteen HCWs tested positive on RT-PCR by NP swab from day 1 to day 12 after the 1st dose administration (incidence rate 6.2 × 10−4) and 5 HCWs from day 13 to day 21 (incidence rate 2.3 × 10−4). Symptom duration and viral clearance timing are significantly shorter in the cohort of HCWs with positive RT-PCR 12 days after the first dose of the BNT162b2 mRNA vaccine. The administration of the first dose proved effective in reducing presence, symptom duration, and viral clearance even in HCWs vaccinated for less than 6 days. These results could have implications on public health and post-exposure prophylaxis.

Healthcare workers are considered at higher risk for mumps infection than the general population. Since 2017, the national immunization plan recommended the administration of a dose of measles–mumps–rubella (MMR) vaccine to the healthcare operators who are unable to demonstrate a complete vaccination history or that are seronegative for at least one of the three agents. Regarding mumps infection, based on actual concerns regarding the loss of protection over the years after vaccination, the Advisory Committee on Immunization Practices (ACIP) recommended to administer a third dose of vaccine to operators previously vaccinated with two doses of MMR vaccine who belong to a group at increased risk of mumps infection in the event of an epidemic. This guideline, however, is not currently followed in Italy, resulting in a potential risk for vaccinated operators to become unprotected from mumps over the years. The aim of our study is to evaluate the persistence of a protective antibody level for mumps among medical students vaccinated during infancy or adolescence, at the start of their hospital internship. We retrospectively evaluated mumps-specific IgG levels in a group of medical students, in the period from 1 January to 31 December 2020. We evaluated the persistence of the detectable level of mumps-specific antibodies in relation to their vaccinal status, gender and time elapsed from vaccination. We found that 17.4% (65 subjects) of our sample were seronegative for mumps. The univariate analysis showed a significant difference in serological protection between male and female gender (77.0% vs. 86.2%, p &lt, 0.05 with chi2 test) and between age classes (86.5% vs. 76.4%, 0.05 for subjects aged 18–23 years and over 23 years, respectively). Female gender was significantly related to higher serological protection even after adjusting for age classes and number of vaccine doses administered in a multivariate analysis model. Our study shows a substantial percentage of subjects lacking a protective mumps titer among medical students who were vaccinated in childhood. Given the higher risk of infection among those subjects, routine pre-employment screening should be performed among those operators regardless of their vaccination history and a third dose of MMR should be offered to unprotected students.

Background: Measles is a highly contagious viral disease with serious complications. Currently, in Italy, measles vaccination is not mandatory for health care workers (HCWs) and medical students, and the free offer of the Measles Mumps Rubella (MMR) vaccine is the only national prevention measure to increase the coverage rate among these subjects. Aims: The aim of our study was to evaluate the impact on vaccination rate of the National Plan of Vaccine Prevention (NPVP) implemented in 2017. Material and Methods: This is a retrospective observational study that evaluated the measles-specific IgG immunity status of medical students at the University Tor Vergata of Rome, which underwent occupational health surveillance from 1 January to 31 December 2018. Results: In 2018, 84 of 319 students (26.30%) were serologically non-immune to measles, among these, 16 (19%) had previously been vaccinated, and 35 of the remaining 68 students accepted the MMR vaccine. Therefore, 33 out of 319 students did not undergo vaccination in 2018. These data are similar to those obtained in the previous year. In the 2017 screening, 84/314 (26.75%) students tested negative at the serological screening, whereas 15/85 (17.8%) among them documented a previous vaccination with two doses of the MMR vaccine, 69 students tested as unprotected. Vaccine compliance was 51.44%. Conclusions: No change in vaccination coverage occurred after the introduction of the last NPVP. Further efforts are needed to sensitize target populations about the relevance of vaccination, providing pre-employment screening for measles and free vaccine might be useful for this purpose.