Corrigendum: 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.

[This corrects the article DOI: 10.3389/fimmu.2022.1079884.].

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.

Attributable Fraction of Cancer Related to Occupational Exposure in Italy.

BACKGROUND: Exposure to occupational carcinogens is an important and avoidable cause of cancer. We aimed to provide an evidence-based estimate of the burden of occupation-related cancers in Italy. METHODS: The attributable fraction (AF) was calculated based on the counterfactual scenario of no occupational exposure to carcinogens. We included exposures classified as IARC group 1 and with reliable evidence of exposure in Italy. Relative risk estimates for selected cancers and prevalences of exposure were derived from large-scale studies. Except for mesothelioma, a 15-20-year latency period between exposure and cancer was considered. The data on cancer incidence in 2020 and mortality in 2017 in Italy were obtained from the Italian Association of Cancer Registries. RESULTS: The most prevalent exposures were UV radiation (5.8%), diesel exhaust (4.3%), wood dust (2.3%) and silica dust (2.1%). Mesothelioma had the largest AF to occupational carcinogens (86.6%), followed by sinonasal cancer (11.8%) and lung cancer (3.8%). We estimated that 0.9% of cancer cases (N~3500) and 1.6% of cancer deaths (N~2800) were attributable to occupational carcinogens in Italy. Of these, about 60% were attributable to asbestos, 17.5% to diesel exhaust, followed by chromium and silica dust (7% and 5%). CONCLUSIONS: Our estimates provide up-to-date quantification of the low, but persistent, burden of occupational cancers in Italy.

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.

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.

Short summary: 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. Background: Persistence of vaccine immunization is key for COVID-19 prevention. Methods: We investigated the difference between two serologic measurements of anti-COVID-19 S1 antibodies in an individual-level analysis on 19,422 vaccinated healthcare workers (HCW) from Italy, Spain, Romania, and Slovakia, tested within 13 months from first dose. Differences in serologic levels were divided by the standard error of the cohort-specific distribution, obtaining standardized measurements. We fitted multivariate linear regression models to identify predictors of difference between two measurements. Results: We observed a progressively decreasing difference in serologic levels from <30 days to 210-240 days. Age was associated with an increased difference in serologic levels. There was a greater difference between the two serologic measurements in infected HCW than in HCW who had never been infected; before the first measurement, infected HCW had a relative risk (RR) of 0.81 for one standard deviation in the difference [95% confidence interval (CI) 0.78-0.85]. The RRs for a 30-day increase in time between first dose and first serology, and between the two serologies, were 1.08 (95% CI 1.07-1.10) and 1.04 (95% CI 1.03-1.05), respectively. The first measurement was a strong predictor of subsequent antibody decrease (RR 1.60; 95% CI 1.56-1.64). Compared with Comirnaty, Spikevax (RR 0.83, 95% CI 0.75-0.92) and mixed vaccines (RR 0.61, 95% CI 0.51-0.74) were smaller decrease in serological level (RR 0.46; 95% CI 0.40-0.54). Conclusions: Age, COVID-19 infection, number of doses, time between first dose and first serology, time between serologies, and type of vaccine were associated with differences between the two serologic measurements within a 13-month period.

Effectiveness of prevention of SARS-CoV-2 transmission among unvaccinated Italian healthcare workers.

BACKGROUND: We aimed to investigate the association between personal protective equipment (PPE) use and SARS-CoV-2 infection among healthcare workers (HCWs). METHODS: We analyzed occupational surveillance contact forms followed by a PCR test notified between March and September 2020 by Italian HCWs. The odds ratios (ORs) and 95% Confidence Intervals (CIs) for positive PCR based on HCWs and contacts characteristics were calculated through multivariable logistic regression models. When multiple contacts were potentially effective for a PCR test, they were weighted by the inverse of their number. RESULTS: Overall, 4,883 contacts reported by 2,952 HCWs were analyzed, and 224 contacts among 144 HCWs had positive PCR. No difference was found according to sex, age, employment, or job title, except for an OR of 0.30 (95%CI 0.11-0.78) for resident physicians, compared to administrative staff. The ORs for use of surgical mask were 0.59 (95%CI=0.40-0.86) for use only by HCW, 0.49 (95%CI=0.22-1.07) only by the infected person, and 0.40 (95%CI=0.27-0.60) by both, compared to use by neither. Use of other PPEs was not associated with infection, while the OR for hand sanitation was 0.61 (95%CI=0.40-0.93). HCWs reporting fever, cough, and asthenia had a higher risk of infection. CONCLUSIONS: Use of surgical masks was associated with a 40-60% lower risk of infection, especially when both HCWs and infected individuals used them. Our results quantify the role played by mask use and hand sanitation in preventing SARS-CoV-2 transmission in high-risk circumstances.

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

Background: 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.

Vaccination Confidence among Healthcare Workers: Results from Two Anamnestic Questionnaires Adopted in the COVID-19 and Influenza Campaign.

BACKGROUND: Following the announcement of the development of COVID-19 vaccines, hesitancy about the safety of vaccinations and their side effects have spread, despite having the approval of international drug agencies. The aim of this study was to test the hypothesis that concern about side effects may have led people to fill out the COVID-19 anamnestic vaccine questionnaire with greater attention compared to the similar instrument used for the influenza vaccination. METHODS: We analyzed vaccination questionnaires of 218 healthcare workers (HCWs) who underwent both COVID-19 and influenza vaccines in 2020/2021. Outcomes included self-reported allergies, chronic pharmacological treatments, and chronic diseases. We tested the difference in prevalence, analyzed differences using the kappa statistics and concordance correlation, and explored factors associated with differences in reporting. RESULTS: HCWs reported more allergies to substances other than drugs and a higher prevalence of chronic drug intake in the COVID-19 questionnaires than in the influenza ones. Technical staff reported more drug allergies than physicians, and other HCWs reported more outcomes than physicians in the COVID-19 questionnaire. CONCLUSIONS: We found that this population of HCWs reported higher conditions during the 2020 COVID-19 vaccination campaign compared to that of the influenza vaccine. The identification of socio-demographic characteristics of the less vaccine-confident HCWs could help in planning targeted interventions to enhance vaccine adherence.

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.

Comparing the Attitude toward the COVID-19 and the 2020/21 and 2019/20 Flu Vaccination Campaigns among Italian Healthcare Workers.

BACKGROUND: While the uptake of the COVID-19 vaccine among healthcare workers (HCWs) is suboptimal, vaccine hesitancy has not been characterized in detail in this population. OBJECTIVE: The aim of this study was to compare the prevalence of health-related conditions reported by HCWs during the COVID-19, 2020/21 flu, and 2019/20 flu vaccination campaigns, so to test the hypothesis that HCWs were more prone to report health conditions during the COVID-19 campaign. METHODS: We analyzed vaccination questionnaires of 176 hospital-based HCWs who underwent the COVID-19 and the 2020/21 flu vaccinations; 2019/20 flu vaccination questionnaires were available for 130 of them. Outcomes included self-reported allergies, chronic diseases, and use of medications. We tested for prevalence equality, analyzed differences using the kappa statistics and concordance correlation, and explored factors associated with differences in reporting. RESULTS: There was no difference in the proportion of HCWs reporting allergies in the three questionnaires, while chronic diseases were more frequently reported in the COVID-19 than in both 2020/21 (p = 0.04) and 2019/20 flu questionnaires (p = 0.02). Furthermore, a higher proportion of HCWs reported medications use in the COVID-19 vaccination questionnaire, compared to both the 2020/21 and the 2019/20 flu vaccination questionnaires (p < 0.001 for both). In each vaccine campaign, women reported more conditions than men, and the difference between chronic disease reports was greater for women than for men. CONCLUSIONS: Our results show more frequent reporting of health conditions during the COVID-19 than the flu vaccination campaigns, providing quantitative evidence of hesitancy of HCWs towards the COVID-19 vaccine.