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.

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.

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.

Evaluation of the Kinetics of Antibody Response to COVID-19 Vaccine in Solid Organ Transplant Recipients: The Prospective Multicenter ORCHESTRA Cohort.

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients' characteristics.

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.