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.].

SARS-CoV-2 Emergency Management in the ASL 1 Abruzzo Companies, Italy: An Autumn 2022 Cross-Sectional Investigation.

BACKGROUND: The SARS-CoV-2 pandemic still represents a public health emergency that affects workplaces and forces employers to develop technical, organizational and procedural measures safeguarding workers' health, particularly 'fragile' ones. This research aimed to assess employers' adherence to the emergency measures planned by the Italian government to hinder COVID-19 during Autumn 2022. METHODS: A cross-sectional study was conducted in Autumn 2022, with an 18-item questionnaire derived from the Italian State's governmental indications, sent by email to 51 companies of Marsica and Peligna Valley, L'Aquila, Southern Italy. RESULTS: A total of 20 recruited companies (65% were micro-enterprises, belonging to the food and financial sector) responded to the questionnaire within a mean time of 18 days (±11.64), which was lower for medium- and large-sized companies as well as for banking sector ones (p < 0.05). As regards intervention strategies, sanitization (92.7% of positive answers) and specific training (83.3%) showed almost full compliance in contrast to working organization (47.5%) and social distancing (61.7%). The companies that reported managing fragility (50%) belong almost exclusively to the banking sector, with predominantly office-based tasks. CONCLUSIONS: The study provided insight into critical issues relating to compliance with national legislative directives and the crucial role of occupational physicians as global advisors for all workplaces.

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.

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.

SARS-CoV-2 and Its Variants in Thrice-Infected Health Workers: A Case Series from an Italian University Hospital.

BACKGROUND: We described a SARS-CoV-2 thrice-infected case series in health workers (HW) to evaluate patient and virus variants and lineages and collect information on variables associated with multiple infections. METHODS: A retrospective analysis of clinical and laboratory characteristics of SARS-CoV-2 thrice-infected individuals was carried out in Verona University Hospital, concurrent with the ORCHESTRA project. Variant analysis was conducted on a subset of available specimens. RESULTS: Twelve HW out of 7368 were thrice infected (0.16%). Symptomatic infections were reported in 63.6%, 54.5% and 72.7% of the first, second and third infections, respectively. Nine subjects were fully vaccinated at the time of the third infection, and five had an additional booster dose. The mean time to second infection was 349.6 days (95% CI, 138-443); the mean interval between the second and third infection was 223.5 days (95% CI, 108-530) (p = 0.032). In three cases, the second and third infections were caused by the Omicron variant, but different lineages were detected when the second vs third infections were sequenced. CONCLUSIONS: This case series confirms evidence of multiple reinfections with SARS-CoV-2, even from the same variant, in vaccinated HW. These results reinforce the need for continued infection-specific prevention measures in previously infected and reinfected HW.

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.

Usefulness and Limitations of Anti-S IgG Assay in Detecting Previous SARS-CoV-2 Breakthrough Infection in Fully Vaccinated Healthcare Workers.

INTRODUCTION: The anti-spike (S) IgG assay is the most widely used method to assess the immunological response to COVID-19 vaccination. Several studies showed that subjects with perivaccination infection have higher anti-S IgG titers. However, a cut-off has not yet been identified so far for distinguishing infected subjects after vaccination. This study thus evaluates the performance of the anti-S IgG assay in identifying subjects with breakthrough infections (BIs) and its potential usefulness for screening healthcare workers (HCWs). METHODS: Out of 6400 HCWs of the University Hospital of Verona vaccinated with two doses of BNT162b2, 4462 never infected before subjects who had completed primary vaccination were tested for IgG anti-S 6 to 9 months after the second dose. Of these, 59 (1.3%) had a BI. The discriminant power of IgG anti-S in detecting previous breakthrough infection was tested by constructing receiver operating characteristic (ROC) curves. RESULTS: The discriminant power for BI was rather good (area under the curve (AUC), 0.78) and increased with decreasing time elapsed between antibody titer assessment and previous SARS-CoV-2 infection. Accuracy (AUC) sensitivity increased from 0.78 (95% CI 0.70-0.85) for BI in the previous six months to 0.83 (95% CI 0.67-0.99) for those in the previous two months, and from 0.68 to 0.80, respectively. The specificity (0.86) and optimal cut-off (935 BAU/mL) remained unchanged. However, BI were rather rare (1.3%), so the positive predictive value (PPV) was low. Only 40 of the 664 HCWs with antibody titer > 935 BAU/mL had previously confirmed BI, yielding a PPV of only 6.0%. When adopting as cut-off the 90th percentile (1180 BAU/mL), PPV increased to 7.9% (35/441). CONCLUSIONS: The anti-S IgG assay displayed good sensitivity and specificity in discriminating subjects with BI, especially in recent periods. However, BIs were rare among HCWs, so that the anti-S IgG assay may have low PPV in this setting, thus limiting the usefulness of this test as a screening tool for HCWs. Further studies are needed to identify more effective markers of a previous infection in vaccinated subjects.

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.

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 vaccination. 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.

Returning to Work after the COVID-19 Pandemic Earthquake: A Systematic Review.

BACKGROUND: The ongoing SARS-CoV-2 pandemic has disrupted life and work habits and has produced landmark changes worldwide. This systematic review aimed to analyse the management of Return to Work (RTW) by work organisations following the virus spread. METHODS: A selection of 2477 papers, using string research on PubMed, Embase, Web of Science and Scopus from January 2020 to October 2021, were analysed. RESULTS: Fifty-one articles were finally included, and the results obtained were discussed from three different points of view. Twenty articles concerning 'Remodelling of Work Organization' proposed some model strategies for resumption to work. Twenty-one papers, including 'Clinical Evaluation of Workers', mostly explored the psychosocial impact of returned workers. Finally, twelve articles explored the best 'Testing Strategies related to RTW'. Despite the heterogeneity of included articles, several interesting approaches have emerged in managing RTW. CONCLUSIONS: The reported experiences could help to develop an RTW model for COVID-19 and future pandemics.

Post-Vaccination SARS-CoV-2 Infections among Health Workers at the University Hospital of Verona, Italy: A Retrospective Cohort Survey.

BACKGROUND: The SARS-CoV-2 vaccination campaign began on 27 December 2020 in Europe, primarily involving health workers. This study aimed to assess the SARS-CoV-2 vaccination effectiveness, as assessed by reductions in incidence, symptom severity, and further infection spreading. METHODS: A retrospective cohort study was conducted on 9811 health workers operating at the Verona University Hospital, Italy, from 27 December 2020 to 3 May 2021. All health workers were offered vaccination with Comirnaty (BNT162b2, BioNTech/Pfizer, Mainz, Germany/New York, United States), and a health surveillance program was implemented with periodical swab testing. Vaccination status and clinical data were collected using an ad hoc semi-structured questionnaire and health surveillance charts. RESULTS: As of 3rd of May, 82.5% of health workers had been vaccinated against SAR-CoV-2, and 177 (1.8%) had tested positive for SARS-CoV-2. Vaccination more than halved the cumulative incidence of SARS-CoV-2 infection and reduced by two-thirds the cumulative incidence of symptomatic subjects. In detail, most unvaccinated HWs were symptomatic; 50% reported fever, 45% reported ageusia/anosmia, and nearly 20% reported dyspnea. These percentages were much lower in HWs who had been vaccinated for at least 14 days (18% for fever and anosmia, 6% for dyspnea and ageusia). Moreover, cases of vaccine breakthrough were sixfold less likely to further spread the infection than unvaccinated HWs. CONCLUSIONS: SARS-CoV-2 vaccination reduced the infection frequency among HWs, further spreading of the infection, and the presence, severity, and duration of COVID-19-related symptoms.

SARS-CoV-2 Infection in Health Workers: Analysis from Verona SIEROEPID Study during the Pre-Vaccination Era.

BACKGROUND: To report the baseline phase of the SIEROEPID study on SARS-CoV-2 infection seroprevalence among health workers at the University Hospital of Verona, Italy, between spring and fall 2020; to compare performances of several laboratory tests for SARS-CoV-2 antibody detection. METHODS: 5299 voluntary health workers were enrolled from 28 April 2020 to 28 July 2020 to assess immunological response to SARS-CoV-2 infection throughout IgM, IgG and IgA serum levels titration by four laboratory tests. Association of antibody titre with several demographic variables, swab tests and performance tests (sensitivity, specificity, and agreement) were statistically analyzed. RESULTS: The overall seroprevalence was 6%, considering either IgG and IgM, and 4.8% considering IgG. Working in COVID-19 Units was not associated with a statistically significant increase in the number of infected workers. Cohen's kappa of agreement between MaglumiTM and VivaDiagTM was quite good when considering IgG only (Cohen's kappa = 78.1%, 95% CI 74.0-82.0%), but was lower considering IgM (Cohen's kappa = 13.3%, 95% CI 7.8-18.7%). CONCLUSION: The large sample size with high participation (84.7%), the biobank and the longitudinal design were significant achievements, offering a baseline dataset as the benchmark for risk assessment, health surveillance and management of SARS-CoV-2 infection for the hospital workforce, especially considering the ongoing vaccination campaign. Study results support the national regulator guidelines on using swabs for SARS-CoV-2 screening with health workers and using the serological tests to contribute to the epidemiological assessment of the spread of the virus.

SARS-CoV-2 emergency in the workplace: are companies ready to protect their workers? A cross-sectional survey.

Purpose. The SARS-CoV-2 pandemic has affected all aspects of everyday life worldwide, including the entire working sector. This study aims to evaluate the response capacity of some Italian companies to the emergency about workers' health and safety. Methods. Data were cross-sectional, collected by a specially drafted 19-item checklist sent to 60 enterprises located in the province of L'Aquila, Abruzzo, Italy. Results. Forty-one companies (68%) responded by filling in the checklist; more than 50% have fewer than 50 employees each and most of the companies belong to the food industry and the financial services. Adherence to the containment measures for the COVID-19 emergency was analysed, especially relating to job organization, social distancing, sanitization and specific training. Large enterprises and the banking sector showed ductile work reorganization according to the containment measures compared to small companies and the food sector. Conclusions. Italian companies have shown a good response to the regulatory restrictions resulting from the SARS-CoV-2 emergency. This is a worthy premise for the imminent management of Phase 2, with the progressive reopening of Italian companies.

Health Surveillance and Response to SARS-CoV-2 Mass Testing in Health Workers of a Large Italian Hospital in Verona, Veneto

Italy presented the first largest COVID-19 outbreak outside of China. Veneto currently ranks fourth among the Italian regions for COVID-19 confirmed cases (~19,000). This study presents health surveillance data for SARS-CoV-2 in 6100 health workers (HW) employed in a large public hospital. Workers underwent oropharyngeal and nasopharyngeal swabs, with a total of 5942 participants (97.5% of the population). A total of 11,890 specimens were tested for SARS-CoV-2 infection using PCR, identifying the viral genes E, RdRP, and N. Positive tests were returned for 238 workers (cumulative incidence of 4.0%, similar in both COVID and nonCOVID units). SARS-CoV-2 risk was not affected by gender, age, or job type, whereas work setting and occupation were both predictors of infection. The risk was higher in medical wards (OR 2.7, 95% CI 1.9-3.9) and health services (OR 4.3, 95% CI 2.4-7.6), and lower in surgical wards and administration areas. To our knowledge, this study represents the largest available HW case list swab-tested for SARS-CoV-2, covering almost the total workforce. Mass screening enabled the isolation of HW, improved risk assessment, allowed for close contacts of and infected HW to return to work, provided evidence of SARS-CoV-2 diffusion, and presented solid ground to prevent nosocomial SARS-CoV-2 infections. The ongoing concurrent sero-epidemiological study aims to enable the improvement of health surveillance to maintain the safety of HWs and the communities they serve.