The Effect of the Immunization Schedule and Antibody Levels (Anti-S) on the Risk of SARS-CoV-2 Infection in a Large Cohort of Healthcare Workers in Northern Italy

Given their occupational risk profile, HCWs were the first to receive anti-SARS-CoV-2 vaccination. However, breakthrough infections remained common, mainly sustained by new SARS-CoV-2 variants of concern (VOCs) that rapidly spread one after another in Italy. Evidence suggests that the measured level of anti-SARS-CoV-2 antibodies does not clearly predict the level of protection conferred by either natural infection or vaccine-induced immunization, highlighting the need for further study on the diversity in susceptibility to SARS-CoV-2 infection. The present study aimed to characterize different risk profiles for SARS-CoV-2 infection in HCWs who had recently received the booster dose, and who were classified according to their immunization profile. The very small number of workers infected during the 8 months following the primary-cycle administration represents proof of the vaccine's effectiveness against non-omicron strains. The comparison among different immunization profiles showed that hybrid immunization (vaccine plus natural infection) elicits higher antibody levels. However, hybrid immunization does not always provide better protection against reinfection, thus suggesting that the immunization profile plays a major role as a virus-host interaction modifier. Despite the high resistance to the reinfection, the peri-booster infection had a not-neglectable infection rate (5.6%), this further reinforcing the importance of preventive measures

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

Determinants of Anti-S Immune Response at 12 Months after SARS-CoV-2 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

Background: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). Methods: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 spike antibodies (IgG) in a cohort of 16,101 vaccinated HCW from eleven centers in Germany, Italy, Romania, Slovakia and Spain. Considering the skewness of the distribution, the serological levels were transformed using log or cubic standardization and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log or cubic antibody level and the corresponding 95% confidence interval (CI) for different factors and combined them in random-effects meta-analyses. Results: We included 16,101 HCW in the analysis. A high antibody level was positively associated with age (RR = 1.04, 95% CI = 1.00-1.08 per 10-year increase), previous infection (RR = 1.78, 95% CI 1.29-2.45) and use of Spikevax [Moderna] with combinations compared to Comirnaty [BioNTech/Pfizer] (RR = 1.07, 95% CI 0.97-1.19) and was negatively associated with the time since last vaccine (RR = 0.94, 95% CI 0.91-0.98 per 30-day increase). Conclusions: These results provide insight about vaccine-induced immunity to SARS-CoV-2, an analysis of its determinants and quantification of the antibody decay trend with time since vaccination

Multimorbidity and Serological Response to SARS-CoV-2 Nine Months after 1st Vaccine Dose: European Cohort of Healthcare Workers-Orchestra Project.

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

Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: An individual-level analysis within 13 months in the ORCHESTRA cohort.

We investigated changes in serologic measurements after COVID-19 vaccination in 19,422 subjects. An individual-level analysis was performed on standardized measurements. Age, infection, vaccine doses, time between doses and serologies, and vaccine type were associated with changes in serologic levels within 13 months

Determinants of Anti-S Immune Response at 9 Months after COVID-19 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

The persistence of antibody levels after COVID-19 vaccination has public health relevance. We analyzed the determinants of quantitative serology at 9 months after vaccination in a multicenter cohort. Methods: We analyzed data on anti-SARS-CoV-2 spike antibody levels at 9 months from the first dose of vaccinated HCW from eight centers in Italy, Germany, Spain, Romania and Slovakia. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log antibody level and the corresponding 95% confidence interval (CI), and combined them in random-effects meta-analyses. Finally, we conducted a trend analysis of 1 to 7 months’ serology within one cohort. Results: We included 20,216 HCW with up to two vaccine doses and showed that high antibody levels were associated with female sex (p = 0.01), age (RR = 0.87, 95% CI = 0.86–0.88 per 10-year increase), 10-day increase in time since last vaccine (RR = 0.97, 95% CI 0.97–0.98), previous infection (3.03, 95% CI = 2.92–3.13), two vaccine doses (RR = 1.22, 95% CI = 1.09–1.36), use of Spikevax (OR = 1.51, 95% CI = 1.39–1.64), Vaxzevria (OR = 0.57, 95% CI = 0.44–0.73) or heterologous vaccination (OR = 1.33, 95% CI = 1.12–1.57), compared to Comirnaty. The trend in the Bologna cohort, based on 3979 measurements, showed a decrease in mean standardized antibody level from 8.17 to 7.06 (1–7 months, p for trend 0.005). Conclusions: Our findings corroborate current knowledge on the determinants of COVID-19 vaccine-induced immunity and declining trend with time. Viruse

Kinematics and biomechanics in normal and replacement elbow

The biomechanics of normal elbow is of primary importance because its comprehension can help the understanding of the functionality of the whole upper limb. The elbow represents a connecting point between the arm and the forearm contributing to modify the relationship between these segments to correctly position the hand in the three-dimensional space. In the following chapter, we will discuss which are the kinematic requirements needed to perform activities of daily living, as well as the impact of muscular actions and external forces on elbow. The final part of the chapter will focus on the role of biomechanics in elbow arthroplasty surgery and its implication in real-life settings