Determinants of anti-S immune response at 6 months after COVID-19 vaccination in a multicentric European cohort of healthcare workers – ORCHESTRA project

Background: The duration of immune response to COVID-19 vaccination is of major interest. Our aim was to analyze the determinants of anti-SARS-CoV-2 IgG titer at 6 months after 2-dose vaccination in an international cohort of vaccinated healthcare workers (HCWs). Methods: We analyzed data on levels of anti-SARS-CoV-2 Spike antibodies and sociodemographic and clinical characteristics of 6,327 vaccinated HCWs from 8 centers from Germany, Italy, Romania and Slovakia. Time between 1st dose and serology ranged 150-210 days. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors, obtaining standardized values. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of 1 standard deviation of log antibody level and corresponding 95% confidence interval (CI), and finally combined them in random-effects meta-analyses. Results: A 6-month serological response was detected in 99.6% of HCWs. Female sex (RR 1.10, 95%CI 1.00-1.21), past infection (RR 2.26, 95%CI 1.73-2.95) and two vaccine doses (RR 1.50, 95%CI 1.22-1.84) predicted higher IgG titer, contrary to interval since last dose (RR for 10-day increase 0.94, 95%CI 0.91-0.97) and age (RR for 10-year increase 0.87, 95%CI 0.83-0.92). M-RNA-based vaccines (p<0.001) and heterologous vaccination (RR 2.46, 95%CI 1.87-3.24, one cohort) were associated with increased antibody levels. Conclusions: Female gender, young age, past infection, two vaccine doses, and m-RNA and heterologous vaccination predicted higher antibody level at 6 months. These results corroborate previous findings and offer valuable data for comparison with trends observed with longer follow-ups

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers.

Background: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. Methods: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). Results: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). Conclusion: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated

One year of sars-cov-2 pandemic: Comparison of infection between health care workers and general population before and after vaccination

Background: The Covid-19 pandemic in Italy has been characterized by three waves of infection during 2020. Vaccination of healthcare workers started in January 2021, earlier than that of other population groups. The main aim of this study is to compare the spread of the pandemic between HCW and the general population focusing on potential effects of the vaccination. Methods:The study consisted of a retrospective analysis of results of RT-PCR tests performed between 6 March 2020 and 4 April 2021 among HCWs from Bologna, Italy, and those of the general population of Emilia Romagna region. We calculated the crude proportion of positive RT-PCR tests over total tests and the crude prevalence of positive test in population; then, we conducted joinpoint analyses using the Joinpoint Regression Program of the National Cancer Institute. Results: The results of the joinpoint analysis show that both ϕ and ψ ratio indicators have a similar pattern, with a sharp increase during the early phase of the pandemic, and a strong decrease at the end of the first wave around week 15. In both indicators there are no significant changes in the trend after week 25. Pandemic spread among HCWs appeared earlier than in the general population, but it oth-erwise appeared to have comparable features. A decline in infection was apparent among HCWs after vaccination. Conclusions: Surveillance of HCWs would inform on the epidemic in the general population. The apparent effectiveness of the anti-SarsCoV2 vaccine will likely occur in the general population

Spatial variability of nitrogen dioxide and formaldehyde and residential exposure of children in the industrial area of Viadana, Northern Italy

Spatial variability of nitrogen dioxide and formaldehyde and residential exposure of children in the industrial area of Viadana, Northern Ital

PVT1: A long non-coding RNA recurrently involved in neoplasia-associated fusion transcripts

NGS technologies and bioinformatics tools allow the rapid identification of chimeric transcripts in cancer. More than 40,000 fusions are so far reported in the literature; however, for most of them, the role in oncogenesis is still not fully understood. This is the case for fusions involving the long non-coding RNA (lncRNA) Plasmacytoma variant translocation 1 (PVT1) (8q24.21). This lncRNA displays oncogenic functions in several cancer types interacting with microRNAs and proteins, but the role of PVT1 fusion transcripts is more obscure. These chimeras have been identified in both hematological malignancies and solid tumors, mainly arising from rearrangements and/or amplification of the 8q24 chromosomal region. In this review, we detail the full spectrum of PVT1 fusions in cancer, summarizing current knowledge about their genesis, function, and role as biomarkers

CircRNAs and Fusion-circRNAs in cancer: New players in an old game

Circular RNAs (circRNAs) are generated from 'back-splicing' events. Their circular structure makes them stable in cells and body fluids. These entities are involved in several human diseases including cancer, as they affect the expression of genes promoting proliferation, invasion, apoptosis, and angiogenesis. Moreover, they are secreted in extracellular vesicles, such as exosomes, having a potential role as messengers in cell-to-cell communications. CircRNAs are also generated by the back-splicing of linear fusion transcripts derived from genomic rearrangements, giving rise to fusion circRNAs (f-circRNAs). Here we discuss the most relevant results achieved by studying the role of circRNAs in cancer onset and progression, particularly focusing on f-circRNAs in hematological and solid tumors. Moreover, we report recent advances in the application of circRNAs as novel “liquid biopsy” biomarkers for early and non-invasive diagnosis of tumors, and as therapeutic targets in human cancer. Their use as engineered molecules sponging oncogenic miRNAs or stably expressing proteins/drugs is also discussed. All these achievements suggest the crucial importance of circRNAs and f-circRNAs in the future setup of personalized therapies in molecular medicine

Serological response after SARS-CoV2 vaccination in healthcare workers: a multicenter study

Introduction: Characterizing immunological response following COVID-19 vaccination is an important public health issue. The objectives of the present analysis were to investigate the proportion, level and the determinants of humoral response from 21 days to three months after the first dose in vaccinated healthcare workers (HCWs). Methods: We abstracted data on level of anti-SARS-CoV-2 Spike antibodies (IgG) and sociodemographic characteristics of 17,257 HCWs from public hospitals and public health authorities from three centers in Northern Italy who underwent COVID-19 vaccination (average 70.6 days after first dose). We fitted center-specific multivariate regression models and combined them using random-effects meta-analyses. Results: A humoral response was elicited in 99.3% of vaccinated HCW. Female sex, young age, and previous COVID-19 infection were predictors of post-vaccination antibody level, and a positive association was also detected with pre-vaccination serology level and with time between pre-and post-vaccination testing, while a decline of antibody level was suggested with time since vac-cination. Conclusions: These results stress the importance of analyzing retrospective data collected via occupational health surveillance of HCWs during the COVID-19 epidemic and following vaccination. They need to be confirmed in larger series based on prospectively collected data