Humoral responses to wild type and ancient BA.1 SARS-CoV-2 variant after heterologous priming vaccination with ChAdOx1 nCoV-19 and BNT162b2 booster dose.

Several countries have recommended a booster dose of Pfizer BNT162b2 vaccine for subjects under the age of 60, who have already received the first dose of ChAdOx1. This is due to several ChAdOx1 vaccine-associated adverse vascular events and thrombocytopenia. Neutralization assay and quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG) were conducted to investigate the long-term responses to vaccine treatment in a cohort of Sardinian participants, who have received heterologous Prime-Boost Vaccination via ChAdOx1 vector vaccine and a booster dose via BNT162b2. The obtained results were compared with those of a cohort of healthcare workers (HCW) who received homologous BNT162b2 (BNT/BNT/BNT) vaccination. One month (T2) and five months after the second and before the third dose (T3), anti-spike antibody or neutralizing titers in the subjects vaccinated with ChAdOx1-S/BNT162b2 were significantly higher than those who experienced the ChAdOx1-S/ChAdOx1-S or BNT162b2/BNT162b2 schedule. These results suggest that a ChAdOx1-S/BNT162b2 regimen provides a more robust antibody response than either of the homologous regimens. However, the anti-spike antibodies or neutralizing titers after the third injection (mRNA vaccine) of ChAdOx1-S as a second dose and BNT162b2 were not statistically different. Homologous and heterologous vaccination provided a strong antibody response. Neutralizing activities were also described against the Omicron BA.1 variant in a sub-group (40) representative of the three vaccination regimens among our cohort.

Impact of Exposure to Vaccination and Infection on Cellular and Antibody Response to SARS-CoV-2 in CVID Patients Through COVID-19 Pandemic.

PURPOSE: The purpose of this study is to investigate the kinetics of response against SARS-CoV-2 elicited by vaccination and/or breakthrough infection (occurred after 3 doses of BNT162b2) in a cohort CVID patients. METHODS: We measured humoral and cellular immunity using quantitative anti-spike antibody (anti-S-IgG) and neutralization assay and specific interferon-gamma release assay (IGRA) before and after the third or fourth dose of BNT162b2 and/or after COVID-19. RESULTS: In CVID, 58.3% seroconverted after 2 doses that increased to 77.8% after 3 doses. Between the second and third dose, there was a decline in humoral compartment that led to titers below the cutoff of 1:10 (MNA90%) in CVID. This was paralleled by a significantly lower proportion (30%) and reduced magnitude of the residual cellular response among CVID. The third dose achieved a lower titer of anti-S and nAb against the Wuhan strain than HC and significantly decreased the rate of those showing solely a positive neutralizing activity and those with simultaneous negativity of IGRA and nAbs; the differences in IGRA were overall reduced with respect to HC. At further sampling after breakthrough SARS-COV-2 infection, mostly in the omicron era, or fourth dose, 6 months after the last event, the residual nAb titer to Wuhan strain was still significantly higher in HC, while there was no significant difference of nAbs to BA.1. The rate of IGRA responders was 65.5% in CVID and 90.5% in HC (p=0.04), while the magnitude of response was similar. None of CVID had double negativity to nAbs and IGRA at the last sampling. CONCLUSION: This data shows an increase of adaptive immunity in CVID after mRNA vaccination in parallel to boosters, accrual number of exposures and formation of hybrid immunity.

A pilot study of occupational exposure to ultrafine particles during 3D printing in research laboratories.

Introduction: 3D printing is increasingly present in research environments, and could pose health risks to users due to air pollution and particulate emissions. We evaluated the nanoparticulate emissions of two different 3D printers, utilizing either fused filament fabrication with polylactic acid, or stereolithography (SLA) with light curing resin. Methods: Nanoparticulate emissions were evaluated in two different research environments, both by environmental measurements in the laboratory and by personal sampling. Results: The SLA printer had higher nanoparticulate emissions, with an average concentration of 4,091 parts/cm3, versus 2,203 particles/cm3 for the fused filament fabrication printer. The collected particulate matter had variable morphology and elemental composition with a preponderance of carbon, sulfur and oxygen, the main byproducts. Discussion: Our study implies that when considering the health risks of particulate emissions from 3D printing in research laboratories, attention should be given to the materials used and the type of 3D printer.

A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G.

Introduction: A large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection. Materials and Methods: We compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy). Results: HLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 - 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3'UTR polymorphism (rs371194629) shows that the HLA-G 3'UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X2 = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X2 = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as ß-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3'UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 - 0.7), PM = 6.5 x 10-4]. Conclusion: Our results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients.

Characterization of upper limb use in health care workers during regular shifts: A quantitative approach based on wrist-worn accelerometers.

Despite the high prevalence of upper limb (UL) work-related musculoskeletal disorders (WRMSD) among health care workers (HCWs), little is known about their relationship with exposure to biomechanical risk factors. This study aimed to assess UL activity features under actual working conditions using two wrist-worn accelerometers. Accelerometric data were processed to obtain duration, intensity, and asymmetry of UL use in 32 HCWs during the execution of commonly performed tasks (e.g., patient hygiene, transfer, and meal distribution) within a regular shift. The results show that such tasks are characterized by significantly different patterns of UL use, in particular, higher intensities and larger asymmetries were observed respectively for patient hygiene and meal distribution. The proposed approach appears, thus, suitable to discriminate tasks characterized by different UL motion patterns. Future studies could benefit from the integration of such measures with self-reported workers' perception to elucidate the relationship between dynamic UL movements and WRMSD.

Musculoskeletal disorders and incongruous postures in workers on ropes: A pilot study.

Background: Occupational hazards believed to cause musculoskeletal disorders in rope workers are traditionally associated with maintaining incongruous postures for prolonged periods of time. Design and methods: A cross-sectional survey was conducted on 132 technical operators in the wind energy and acrobatic construction sectors, who work on ropes, analysing the ergonomic characteristics of the environments, the way in which tasks are carried out, the strain perceived by individual workers, and assessing the presence of any musculoskeletal disorders (MSDs) by means of an objective examination focused on the anatomical districts that were the object of our study. Results: Analysis of the data obtained showed that there were differences in the perception of the level of physical intensity and perceived exertion between the groups of workers. Statistical analysis also revealed a significant association between the frequency of MSDs analysed and perceived exertion. Discussion: The most significant finding to emerge from this study is the high prevalence of MSDs of the cervical spine (52.94%), the upper limbs (29.41%), and the dorso-lumbar spine (17.65%). These values differ from those classically found in those exposed to the risk of conventional manual handling of loads. Conclusions: The high prevalence of disorders of the cervical spine, the scapulo-humeral girdle and the upper limbs, indicates the need to consider the forced position to be assumed for a large part of the work activity, staticity, and the inability to move the lower limbs for long periods as the predominant risk in rope work.

COVID-19 Vaccine Hesitancy among Italian Healthcare Workers: Latent Profiles and Their Relationships to Predictors and Outcome.

Vaccine hesitancy and conspiracy beliefs among healthcare workers (HCWs) represent operational priorities that require urgent attention. Identifying and classifying specific subpopulation of hesitancy is crucial to customize educational and intervention strategies to enhance the acceptance and uptake rate of vaccination. Thus, the main purpose of our study was to empirically identify latent profiles of vaccine hesitancy among Italian HCWs adopting a person-centered approach and investigating their relationships with antecedents and intention to get a fourth dose of COVID-19 vaccine. We conducted latent profile analyses (LPA) to identify different configurations of vaccine hesitancy based on five antecedents of vaccination: confidence, complacency, constraints, calculation, and collective responsibility among a sample of Italian HCWs (n = 573). LPA revealed four distinct profiles: believer (61.5%), middler (24.7%), hesitant (9.00%), and rejecter (4.7%). Having conspiracy beliefs was associated with a greater likelihood of membership in all but believer. Finally, the likelihood of intention to get a fourth dose of COVID-19 vaccine was lowest in the rejector and hesitant profiles. Theoretical contributions and implications for practice are discussed.

Evaluation of Correlation between Sleep and Psychiatric Disorders in a Population of Night Shift Workers: A Pilot Study.

BACKGROUND: Insomnia is the perception of inadequate, insufficient or non-restorative sleep. Of all sleep-related disorders, insomnia is the most common. It is important to remember that the sleep-wake cycle also plays a central role in the genesis of anxiety and depression. The aim of our study is to evaluate the association between sleep disturbances and anxiety and depression in a group of workers of both sexes who perform night shift work. METHODS: Information on sleep disorders was collected by administering the Insomnia Severity Index (ISI) questionnaire. Statistical analysis was conducted using the Chi-square test to assess whether there were any differences between sex for those who were healthy or who were diagnosed with psychiatric disorders. RESULTS: The results showed that there was a good percentage of subjects with insomnia problems, impairing normal daily activities and promoting the onset of fatigue, daytime sleepiness, cognitive performance deficits and mood disorders. CONCLUSION: We highlighted how anxious and depressive anxiety disorders are more pronounced in people who suffer from altered sleep-wake rhythms. Further research in this direction could prove to be fundamental for understanding the genesis of the onset of other disorders as well.

Impact of occupational categories on the incidence of amyotrophic lateral sclerosis in Sardinia Island, Italy.

OBJECTIVE: Occupation is one of the potential risk factors for amyotrophic lateral sclerosis (ALS) for which previous controlled studies produced inconsistent results. The aim of this study is to assess the impact of several groups of occupational categories on ALS incidence. METHODS: ALS patients from the southern part of Sardinia who had onset during 2012-2021 and fulfilled El Escorial revised diagnostic criteria were included. The risk of ALS was estimated in relation to the occupation held in 2011, as obtained from the 2011 Census that classified working activities in ten groups. Each occupational group was compared with a reference category represented by all other occupations, and rate ratio were calculated. Additive interaction between activity at work and age at ALS onset/sex on ALS incidence was calculated. RESULTS: Employment in agriculture/breeding and in the armed forces were significantly associated with increasing ALS risk. None of the other assessed occupation groups was associated with change in the risk of ALS. Geographic analysis indicated that the effect of agriculture/breeding was particularly evident in the areas of higher risk for the general population. By contrast, an inverse pattern of spatial risk was associated with armed forces activity at work. The increased risk of ALS associated to agriculture/breeding was more evident in older people. No significant interaction was detected between working in the armed forces and older age/sex. CONCLUSIONS: The significant interaction between agriculture/breeding and age suggests that the mechanisms leading to ALS are complex and involve several factors.

Continuous assessment of trunk posture in healthcare workers assigned to wards with different MAPO index.

Healthcare professionals generally experience an above-average incidence of low back disorders (LBDs) compared with workers of other professions, and its level of risk is commonly assessed using observational methods such as the MAPO method (Movement and Assistance of Hospital Patients). In this study, we continuously monitored the trunk posture of 30 healthcare workers using a single inertial sensor to: (1) understand whether the MAPO classification is effective in adequately discriminating the risk associated with the time spent in non-neutral trunk postures and (2) characterise the variability of biomechanical exposure among workers employed in wards with the same MAPO index. The results substantially confirm the validity of the MAPO approach in discriminating among wards characterised by different levels of biomechanical exposure associated with the risk of developing LBDs. However, they also highlight the need to assess workers' exposure on an individual basis due to the high intra-group variability.Practitioner summary: Employing a quantitative measurement setup to monitor trunk posture along with an observational method (ie MAPO) can identify the existence of criticalities or the poor application of ergonomic recommendations given during the training of healthcare workers even in hospital wards characterised by little or no risk of developing low back disorders.

Ocular Surface Changes Associated with Face Masks in Healthcare Personnel during COVID-19 Pandemic.

The aim of this study was to investigate ocular surface changes associated with face mask (FMs) use of healthcare personnel during the COVID-19 pandemic. We prospectively evaluated 200 eyes of 100 individuals during working hours and 40 eyes of 20 individuals during their rest days as a control group. Dry eye symptoms were assessed with the Ocular Surface Disease Index (OSDI) and McMonnies questionnaire. The clinical investigation included the best corrected visual acuity (BCVA), corneal fluorescein staining (FS), break-up time (BUT), and Schirmer test I before and after a 7-h work shift with a continuative use of surgical or N95 masks. The control group was evaluated similarly twice a day, at 8:00 a.m. and at 3:00 p.m.. In the study group, BCVA, FS, BUT, and Schirmer test were investigated and there was a significant negative variation at the end of the shift. On the contrary, the control group did not show significant variations of any clinical feature. Furthermore, no significant changes in clinical parameters were observed during the use of surgical or N95 masks. In conclusion, FMs continuative use resulted in daily ocular surface modifications specifically in healthcare personnel.

Evaluation of humoral and cellular response to third dose of BNT162b2 mRNA COVID-19 vaccine in patients treated with B-cell depleting therapy.

OBJECTIVE: to investigate the responses to mRNA COVID-19 vaccines in a cohort of immunosuppressed patients affected by immune-mediated inflammatory diseases (IMID). METHODS: we have measured humoral and cellular immunity using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assays and specific interferon-gamma (IFN-g) release assay (IGRA) before and after the third dose of BNT162b2. The response of those on anti-CD20 (n = 18) was then compared with healthy controls (HC, n = 18) and IMID naïve to anti-CD20 drugs (n = 13). RESULTS: a third BNT162b2 dose is highly immunogenic in IMID patients naïve to anti-CD20, as 100% of the subjects seroconverted compared to the 55% in anti-CD20. The rate of IGRA response was of 79% in anti-CD20, 50% in IMID naïve to anti-CD20, 100% in HC. Among those who have seroconverted, IMID patients had significantly reduced anti-S-IgG and neutralization titers compared to HC, whereas no significant difference was observed when comparing anti-CD20 and HC. Furthermore, 13% of anti-CD20 and 7.7% of IMID were simultaneously negative for both neutralizing antibodies and IGRA after three doses. CONCLUSION: these data draw attention to the immunogenicity of COVID-19 vaccination in treated IMID, taking specific groups into consideration for vaccination program.

A Protective HLA Extended Haplotype Outweighs the Major COVID-19 Risk Factor Inherited From Neanderthals in the Sardinian Population.

Sardinia has one of the lowest incidences of hospitalization and related mortality in Europe and yet a very high frequency of the Neanderthal risk locus variant on chromosome 3 (rs35044562), considered to be a major risk factor for a severe SARS-CoV-2 disease course. We evaluated 358 SARS-CoV-2 patients and 314 healthy Sardinian controls. One hundred and twenty patients were asymptomatic, 90 were pauci-symptomatic, 108 presented a moderate disease course and 40 were severely ill. All patients were analyzed for the Neanderthal-derived genetic variants reported as being protective (rs1156361) or causative (rs35044562) for severe illness. The ß°39 C>T Thalassemia variant (rs11549407), HLA haplotypes, KIR genes, KIRs and their HLA class I ligand combinations were also investigated. Our findings revealed an increased risk for severe disease in Sardinian patients carrying the rs35044562 high risk variant [OR 5.32 (95% CI 2.53 - 12.01), p = 0.000]. Conversely, the protective effect of the HLA-A*02:01, B*18:01, DRB*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 - 41.0), p < 0.0001]. This result suggests that the balance between risk and protective immunogenetic factors plays an important role in the evolution of COVID-19. A better understanding of these mechanisms may well turn out to be the biggest advantage in the race for the development of more efficient drugs and vaccines.

Neutralizing Antibodies Responses against SARS-CoV-2 in a Sardinian Cohort Group Up to 9 Months after BNT162b2 Vaccination.

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has caused over 460 million cases of infection and over 6 million deaths worldwide. The pandemic has called for science, technology, and innovation to provide solutions and, due to an incredible scientific and financial global effort, several prophylactic and therapeutic apparatuses such as monoclonal antibodies and vaccines were developed in less than one year to address this emergency. After SARS-CoV-2 infection, serum neutralizing antibodies are produced by B cells and studies on virus-neutralizing antibodies' kinetics are pivotal. The process of protective immunity and the duration of this kind of protection against COVID-19 remain to be clarified. We tested 136 sera from 3 groups of individuals, some of them providing multiple sequential sera (1-healthy, no previous CoV2-infected, vaccinated; 2-healthy, previous CoV2 infected, vaccinated; 3-healed, previous CoV2-infected, not vaccinated) to assess the kinetics of antibodies (Abs) neutralizing activity. We found that SARS-CoV-2 infection elicits moderate neutralizing antibody activity in most individuals; neither age nor gender appear to have any influence on Abs responses. The BNT162b2 vaccine, when administered in two doses, induces high antibodies titre endowed with potent neutralizing activity against bare SARS-CoV-2 in in vitro neutralizing assay. The residual neutralization capability and the kinetic of waning immunity were also evaluated over 9 months after the second dose in a reference group of subjects. Neutralization titre showed a decline in all subjects and the median level of S-protein IgG, over 270 days after the second vaccination dose, was below 10 AU/mL in 53% of serum tested.

Responsiveness and minimal important change of the Pain Catastrophizing Scale in people with chronic low back pain undergoing multidisciplinary rehabilitation.

BACKGROUND: The Pain Catastrophizing Scale (PCS), a widely used tool to assess catastrophizing related to spinal disorders, shows valid psychometric properties in general but the minimal important change (MIC) is still not determined. AIM: The aim of this study was to assess responsiveness and MIC of the PCS in individuals with chronic low back pain (LBP) undergoing multidisciplinary rehabilitation. DESIGN: Prospective observational study. SETTING: The setting was outpatient rehabilitation hospital. POPULATION: Two hundred and five patients with chronic LBP. METHODS: Before and after an 8-week multidisciplinary rehabilitation program, 205 patients completed the Italian version of the PCS (PCS-I). We calculated the PCS-I responsiveness by distribution-based methods (effect size [ES], standardized response mean [SRM], and minimum detectable change [MDC]) and anchor-based methods [receiver operating characteristic (ROC) curves]. After the program, participants completed a 7-point global perceived effect scale (GPE), based on which they were classified as "improved" vs. "stable." ROC curves computed the best cut-off level (taken as the MIC) between the two groups. ROC analysis was also performed on subgroups according to patients' baseline PCS scores. RESULTS: ES, SRM and MDC were 0.71, 0.67 and 7.73, respectively. ROC analysis yielded an MIC of 8 points (95% confidence interval [CI]: 6-10; area under the curve [AUC]: 0.88). ROC analysis of the PCS subgroups confirmed an MIC of 8 points (95%CI: 6-10) for no/low catastrophizers (score <30, N.=159; AUC: 0.90) and indicated an MIC of 11 points (95%CI: 8-14) for catastrophizers (score >30, N.=33; AUC: 0.84). CONCLUSIONS: The PCS-I showed good ability to detect patient-perceived clinical changes in chronic LBP postrehabilitation. The MIC values we determined provide a benchmark for assessing individual improvement in this clinical context. CLINICAL REHABILITATION IMPACT: The present study calculated - in a sample of people with chronic LBP - the responsiveness and MIC of the PCS. These values increase confidence in interpreting score changes, enhancing their meaningfulness for both research and clinical contexts.

Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination.

SARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p < 0.001). IMID patients had a significantly different level of IgG than HCW at both T1 (p = 0.031), T2 (p < 0.001), while there was no significant difference at T3. There were no statistically significant differences according to the IMID type or to ongoing treatment with immunosuppressants, corticosteroids or biological drugs other than anti-CD20. The proportion and magnitude of response was significantly lower in IMID treated with anti-CD20 drugs. There was a correlation with age at T1 and at T2 but not at T3, stronger in patients than in HCW. Immune response close after BNT162b2 vaccination is reduced in patients with IMID, but there is no significant difference at 5 months. The measured reduction is related to age and the disease itself rather than treatments, with the exception of anti-CD20 drugs.

Evaluation of Antibody Response to Heterologous Prime-Boost Vaccination with ChAdOx1 nCoV-19 and BNT162b2: An Observational Study.

In several countries, thrombotic events after vaccination with ChAdOx1 nCoV-19 have led to heterologous messenger RNA (mRNA) boosting. We tested the antibody response to SARS-CoV-2 spike protein four weeks after heterologous priming with the ChAdOx1 (ChAd) vector vaccine followed by boosting with BNT162b2(ChAd/BNT), comparing data of homologous regimen (BNT/BNT, ChAd/ChAd) subjects positive for SARS-CoV-2 after the first dose of BNT162b2 (BNT1dose/CoV2) and convalescent COVID-19. METHODS: healthy subjects naïve for SARS-CoV-2 infection were assessed for serum IgG anti-S-RBD response 21 days after priming (T1), 4 (TFULL) and 15 (T15W) weeks after booster dose. RESULTS: The median IgG anti-S-RBD levels at TFULL of Chad/BNT group were significantly higher than the BNT/BNT group and ChAd/ChAd. Those of BNT/BNT group were significantly higher than ChAd/ChAd. IgG anti-S-RBD of BNT1dose/CoV2 group were similar to BNT/BNT, ChAd/BNT and ChAd/Chad group. The levels among COVID-19 convalescents were significantly lower than ChAd/BNT, BNT/BNT, ChAd/Chad and BNT1dose/CoV2. The proportion of subjects reaching an anti-S-RBD titer >75 AU/mL, correlated with high neutralizing titer, was 94% in ChAd/BNT and BNT/BNT, 60% in BNT1dose/CoV2, 25% in ChAd/ChAd and 4.2% in convalescents. At T15W the titer of ChAd/BNT was still significantly higher than other vaccine schedules, while the anti-S-RBD decline was reduced for ChAd/ChAd and similar for other combinations. CONCLUSION: Our data highlight the magnitude of IgG anti-S-RBD response in ChAd/BNT dosing, supporting the current national guidelines for heterologous boosting.

Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy.

An increasing number of pathologies correlates with both toxic and essential metal ions dyshomeostasis. Next to known genetic disorders (e.g., Wilson's Disease and ß-Thalassemia) other pathological states such as neurodegeneration and diabetes are characterized by an imbalance of essential metal ions. Metal ions can enter the human body from the surrounding environment in the form of free metal ions or metal-nanoparticles, and successively translocate to different tissues, where they are accumulated and develop distinct pathologies. There are no characteristic symptoms of metal intoxication, and the exact diagnosis is still difficult. In this review, we present metal-related pathologies with the most common onsets, biomarkers of metal intoxication, and proper techniques of metal qualitative and quantitative analysis. We discuss the possible role of drugs with metal-chelating ability in metal dyshomeostasis, and present recent advances in therapies of metal-related diseases.

Seroepidemiology of Measles, Mumps, Rubella and Varicella in Italian Female School Workers: A Cross-Sectional Study.

BACKGROUND: Determining the proportion of susceptible workers can represent a first step to the biological risk assessment related to measles, mumps, rubella and varicella exposure. This study aimed to assess the immunity against measles, mumps, rubella and varicella viruses in a cohort of female school workers. METHODS: A cross-sectional seroepidemiological study in a sample of 263 school workers undergoing routine annual workplace health surveillance program was conducted. As part of the health surveillance program, serum samples were collected and tested for measles, mumps, rubella and varicella IgG antibodies. RESULTS: Overall seropositivity was 90.5%, 85.2%, 94.7% and 97.3% for measles, mumps, rubella and varicella, respectively. In relation to mumps occupation-specific seropositivity, a statistically significant difference was observed, showing the lowest prevalence of protected individuals in other occupation groups. Moreover, in relation to rubella, school workers born in Centre Italy had the lowest seropositivity of protective antibodies and the difference between groups was statistically significant. Measles and rubella seropositivity showed a significant decrease after 2015. CONCLUSIONS: This study showed a relevant proportion of school workers susceptible to the aforementioned diseases. These results highlighted the need for proper health surveillance and immunological controls in school workers, especially for females, and provided useful insights to policymakers to select effective strategies aimed at containing the risk of vaccine-preventable diseases at schools.

Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection.

BACKGROUND: The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. METHODS: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. RESULTS: Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]. CONCLUSIONS: The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection.