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PURPOSE: Anti SARS-CoV-2 vaccination initially showed high effectiveness in preventing COVID-19. However, after the surge of variants of concern, the effectiveness dropped. Several studies investigated if this was related to the decrease of the humoral response over time; however, this issue is still unclear. The aim of this study was to understand whether SARS-CoV-2 anti-S IgG levels can be used to predict breakthrough infection risk and define the timing for further booster doses administration. METHOD: Within the framework of the ORCHESTRA Project, over 20,000 health workers from 11 European centers were enrolled since December 2020. We performed two Cox proportional hazards survival analyses regarding pre-Omicron (from January to July 2021) and Omicron (December 2021-May 2022) periods. The serological response was classified as high (above the 75th percentile), medium (25th-75th), or low (< 25th). RESULTS: Seventy-four (0.33%) and 2122 (20%) health workers were infected during the first and second periods, respectively. Both Cox analyses showed that having high anti-S titer was linked to a significantly lower risk of infection as compared to having medium serological response [HR of high vs medium anti-S titer = 0.27 (95% CI 0.11-0.66) during the first phase, HR = 0.76 (95% CI 0.62-0.93) during the second phase]. CONCLUSION: Vaccine effectiveness wanes significantly after new variants surge, making anti-S titer unsuitable to predict optimal timing for further booster dose administration. Studies on other immunological indicators, such as cellular immunity, are therefore needed to better understand the mechanisms and duration of protection against breakthrough infection risk.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Personal de Salud , Inmunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Personal de Salud/estadística & datos numéricos , SARS-CoV-2/inmunología , Europa (Continente)/epidemiología , Inmunoglobulina G/sangre , Anticuerpos Antivirales/sangre , Femenino , Adulto , Masculino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Persona de Mediana Edad , Inmunización Secundaria , Glicoproteína de la Espiga del Coronavirus/inmunología , Infección IrruptivaRESUMEN
BACKGROUND: The SARS-CoV-2 pandemic greatly impacted healthcare workers (HCWs) dedicated to caring for COVID-19 patients. The study was conducted in a large European hospital to study the psychological distress of HCWs engaged in COVID-19 wards in the early phase of the pandemic. METHODS: A questionnaire was sent to 1229 HCWs aimed at collecting the following information: 1) sociodemographic data; 2) depression, anxiety, and stress scales (DASS-21); 3) event impact scale (IES-R); 4) perceived stress scale (PSS); and 5) work interface analysis. The responses were collected through Google® forms and then statistically analyzed. Regardless of the outcome of the questionnaire, all subjects were offered psychological support voluntarily. RESULTS: Approximately two-thirds of the workers reported no symptoms according to the DASS-21 scales, while the IES-R and PSS scales showed 36% and 43%, respectively. There were no statistically significant differences in the levels of depression investigated through the different scales in the various occupational categories. Symptoms of anxiety, stress, and depression were more pronounced in women, while the highest stress levels were observed in the younger age groups. The highest scores were observed on the DAS-21 scales of anxiety and IES-R but not on the others. Only 51 workers, most of them with previous SARS-CoV-2 infection, sought clinical psychological counseling, and more than half received subsequent psychological support. CONCLUSIONS: Our results agree with most of the literature data that anxiety, depression, and stress are associated with gender (female), age (18-44 vs. over 55), and having cared for patients with COVID-19.
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COVID-19 , Bienestar Psicológico , Femenino , Humanos , Ansiedad/epidemiología , COVID-19/epidemiología , Estudios Transversales , Depresión/epidemiología , Personal de Salud/psicología , Hospitales , Salud Mental , SARS-CoV-2RESUMEN
BACKGROUND: Health care workers (HCWs) were on the frontline of the current pandemic. We aimed at identifying determinants of SARS-CoV-2 infection and the effectiveness of personal protection equipment (PPE) worn by HCWs before vaccination. METHODS: We abstracted data on SARS-CoV-2 infection based on positive PCR results and sociodemographic characteristics of 38,793 HCWs from public hospitals and public health authorities from 10 European centers. We fitted cohort-specific multivariate logistic regression models to identify determinants of infection and combined the results using random-effects meta-analyses. RESULTS: The overall prevalence of infection before vaccination among HCWs was 9.58%. Infection was associated with the presence of selected symptoms; no association was found between sociodemographic factors and increased risk of infection. The use of PPE and particularly FFP2/FFP3 masks had a different protective effect during the first and second waves of the COVID pandemic. CONCLUSIONS: The study provides evidence that mask use was the most effective PPE in preventing SARS-CoV-2 infection among HCWs.
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COVID-19 , Humanos , SARS-CoV-2 , Vacunación , Personal de Salud , PandemiasRESUMEN
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.
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COVID-19 , ARN Viral , Anticuerpos Antivirales , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Femenino , Personal de Salud , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Vacunación/métodosRESUMEN
BACKGROUND: Dental technicians are at high risk of pneumoconiosis, usually driven by inhalation of mixed dusts, including metals. An etiological diagnosis is not easy to be performed, particularly in advanced stages. CASE PRESENTATION: We describe the case of an early pneumoconiosis occurring in a 47-year-old dental technician who developed respiratory symptoms shortly after beginning work. She described the work environment as dusty and lacking relevant primary prevention tools. A chest CT showed multiple peripheral pseudonodular lesions in both lower lobes; bronchoalveolar lavage and bronchial aspirate evidenced numerous macrophages with reflective metal bodies included into the cytoplasm, that at scanning electron microscopy coupled to Energy Dispersive X-Ray Analysis resulted Zirconium and Aluminum, whereas Tungsten (W) was localized outside cells. End of shift urinary concentrations of W were substantially raised as compared to pre-shift (1.1 vs. 0.2 µg/L). CONCLUSIONS: We concluded for diagnosis of early work-related pneumoconiosis due to abnormal occupational exposure to metals. The case demonstrates the need also for dental professionals to comply with industrial hygiene standards and to be monitored by occupational health physicians.
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Metales Pesados/efectos adversos , Exposición Profesional/efectos adversos , Neumoconiosis/etiología , Técnicos Dentales , Polvo , Humanos , Italia , Persona de Mediana Edad , Neumoconiosis/diagnóstico por imagen , Neumoconiosis/patologíaRESUMEN
BACKGROUND: The present study was aimed at evaluating the effectiveness of BNT162b2 among HCWs of a university hospital while a recrudescence of pandemics was hitting the province, with a high rate of the B.1.1.7 variant. Methods: The study was performed in the context of health surveillance at the workplaces. We monitored the SARS-CoV-2 infection and COVID-19 symptoms among HCWs classified by having received the entire vaccine schedule or not; the latter further classified in not vaccinated workers and workers who had received the first shot more than 14 days earlier. The SARS-CoV-2 infection was diagnosed by conventional RT-PCR on rhino-pharyngeal swabs, followed by gene sequencing in positive vaccinated HCWs. The cumulative incidence of infections in the period was normalised to 100,000 people. Results: At the end of the observation period, HCWs that had completed the full schedule were at lower infection risk than both unvaccinated HCWs and the workforce who had not yet gained the complete theoretical protection from the vaccine (by 2.4-folds). Overall, ninety-two SARS-CoV-2 infections were observed among HCWs, mostly among not protected workers (52 cases) but none of them showed symptoms requiring hospitalisation. Conclusions: The vaccination campaign effectively reduced the appearance of symptoms and the incidence of infections among vaccinated HCWs. Among vaccinated HCWs, gene sequencing was possible in five cases only, 4 B.1.1.7 and 1 B1.525 variants. The high rate of unsuccessful gene sequencing observed among infected vaccinated workers could be explained by a low viral burden. Vaccination for COVID-19 should be mandatory in occupational settings with a high infective risk.
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COVID-19 , SARS-CoV-2 , Vacuna BNT162 , Vacunas contra la COVID-19 , Personal de Salud , HumanosRESUMEN
COVID-19 vaccines elicit a strong anti-S antibodies response. We aim to describe antibody titers in peri-vaccination SARS-CoV-2 infections. This is a retrospective longitudinal single-cohort study. Serological tests were performed at the time of the first SARS-CoV-2 vaccine dose (T0) and 60 (T1), 120 (T2), and 240 (T3) days after. The study included 4,682 subjects. Group A had the infection without an anti-S Ig response. Group B and C seroconverted for anti-N Ig between T0 and T1 and between T1 and T2, respectively. Group D was persistently anti-N Ig negative. Group B showed an initial sub-optimal response, reaching the highest titer at T3. Those who received the second dose 120 days after the infection had higher titers compared to those who received it 21 days after the first dose. The immune response depends on the number and the timing of vaccine doses, highlighting the need for a more personalized approach to vaccination.
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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.
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The remarkable variability of response to vaccines against SARS-CoV-2 is apparent. The present study aims to estimate the extent to which the host genetic background contributes to this variability in terms of immune response and side effects following the administration of the BNT162b2 vaccine. We carried out a genome wide association study (GWAS) by genotyping 873 Italian healthcare workers who underwent anti-SARS-CoV-2 vaccination with the BNT162b2 vaccine and for whom information about anti-SARS-CoV-2 spike antibodies titers and vaccine side effects were available. The GWAS revealed a significant association between the HLA locus and the anti-SARS-CoV-2 Spike antibodies level at 2 months following the first dose of vaccine (SNP: rs1737060; p = 9.80 × 10-11 ). In particular, we observed a positive association between the antibody levels and the presence of the HLA-A*03:01 allele. The same allele was found associated with a 2-2.4-fold increased risk of experiencing specific side effects such as fever, chills and myalgia and a 1.5-1.8-fold increased risk of joint pain, nausea, fatigue, headache and asthenia, independently of age and sex. This study confirms that the heterogeneity in the immune response to the BNT162b2 vaccine and in its side effects are at least partially influenced by genetic variants. This information, integrated with individual biological and lifestyle-related correlates, could be of use in the definition of algorithms aimed at the identification of subjects in which the administration of additional vaccine doses would be particularly beneficial to maintain immunity against the virus.
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Estudio de Asociación del Genoma Completo , Vacunas , Humanos , Alelos , Vacuna BNT162 , Vacunas contra la COVID-19/efectos adversos , Anticuerpos Antivirales , Personal de Salud , Antígenos HLA-ARESUMEN
[This corrects the article DOI: 10.3389/fimmu.2022.1079884.].
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BACKGROUND: SARS-CoV-2 breakthrough infections (BI) after vaccine booster dose are a relevant public health issue. METHODS: Multicentric longitudinal cohort study within the ORCHESTRA project, involving 63,516 health workers (HW) from 14 European settings. The study investigated the cumulative incidence of SARS-CoV-2 BI after booster dose and its correlation with age, sex, job title, previous infection, and time since third dose. RESULTS: 13,093 (20.6%) BI were observed. The cumulative incidence of BI was higher in women and in HW aged < 50 years, but nearly halved after 60 years. Nurses experienced the highest BI incidence, and administrative staff experienced the lowest. The BI incidence was higher in immunosuppressed HW (28.6%) vs others (24.9%). When controlling for gender, age, job title and infection before booster, heterologous vaccination reduced BI incidence with respect to the BNT162b2 mRNA vaccine [Odds Ratio (OR) 0.69, 95% CI 0.63-0.76]. Previous infection protected against asymptomatic infection [Relative Risk Ratio (RRR) of recent infection vs no infection 0.53, 95% CI 0.23-1.20] and even more against symptomatic infections [RRR 0.11, 95% CI 0.05-0.25]. Symptomatic infections increased from 70.5% in HW receiving the booster dose since < 64 days to 86.2% when time elapsed was > 130 days. CONCLUSIONS: The risk of BI after booster is significantly reduced by previous infection, heterologous vaccination, and older ages. Immunosuppression is relevant for increased BI incidence. Time elapsed from booster affects BI severity, confirming the public health usefulness of booster. Further research should focus on BI trend after 4th dose and its relationship with time variables across the epidemics.
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COVID-19 , Femenino , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Incidencia , SARS-CoV-2 , Vacuna BNT162 , Infección Irruptiva , Estudios LongitudinalesRESUMEN
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.
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A virtual screening procedure was applied to the discovery of structurally diverse non-steroidal Farnesoid X Receptor (FXR) agonists. From 117 compounds selected by virtual screening, a total of 47 compounds were found to be FXR agonists, with 34 of them showing activity below a concentration of 20 µM. 1H-Pyrazole[3,4-e][1,4]thiazepin-7-one-based hit compound 7 was chosen for hit-to-lead optimization. A large number of 1H-pyrazole[3,4-e][1,4]thiazepin-7-one derivatives was designed, synthesized, and evaluated by a cell-based luciferase transactivation assay for their agonistic activity against FXR. Most of them exhibited low micromolar range of potency and very high efficacy.
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Pirazoles/química , Receptores Citoplasmáticos y Nucleares/agonistas , Relación Estructura-Actividad , Tiazepinas/síntesis química , Tiazepinas/farmacología , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Evaluación Preclínica de Medicamentos/métodos , Perfilación de la Expresión Génica , Células Hep G2 , Humanos , Luciferasas/genética , Luciferasas/metabolismo , Modelos Moleculares , Estructura Molecular , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Interfaz Usuario-ComputadorRESUMEN
Objective: To evaluate the information collected from workers infected with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) or close contacts using a digital data gathering system (DDGS) developed at the onset of the coronavirus disease 2019 (COVID-19) pandemic to better manage the spread of infection at our hospital. Design: Observational retrospective study. Setting: Tertiary University Hospital "Spedali Civili" Hospital, Brescia, Italy. Participants: Workers (most of whom are healthcare workers) employed at the hospital. Methods: The information collected by the DDGS was transferred to the IBM SPSS statistical software package and then statistically analyzed. Results: Overall, â¼16% of the hospital workforce was infected by SARS-CoV-2 in the first pandemic wave. Nurses were the professional category with the highest infection rate (â¼15%). The asymptomatic rate of infection was between 31% and 62%. Positive molecular swabs were significantly more frequent in workers undergoing the test after sending a signaling form to our DDGS. Among workers sending the signaling forms, the information about symptoms was more predictive in terms of risk, compared to the close-contact information. The concordance between molecular swabs and subsequent serological testing was significantly higher in workers signaling their at-risk condition through the DDGS. Conclusions: Overall, our data demonstrate the advantages of a digital system to gather information from workers, which is useful for managing emergencies such as the COVID-19 pandemic. This holds particularly true for large organizations such as hospitals.
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OBJECTIVES: This is a longitudinal prospective study which was designed to assess the trend of anti-SARS-CoV-2 antibodies targeting the Spike (anti-S) and Nucleocapside protein (anti-N) viral antigens over a 9-month period after the administration of an anti-SARS-CoV-2 vaccine in a big COVID-19 hospital located in Northern Italy. PARTICIPANTS: 7411 vaccinated workers were included in a linear mixed-effect model analysis performed to model the anti-S decay over the 9 months following the vaccination, during serological screening performed approximately 2, 4, and 9 months following the first jab administration. Serological tests performed in the 9 months preceding vaccine administration were retrospectively analysed to identify the burden of infections occurring before vaccination. RESULTS: The serological assays were used for monitoring the antibody titres during the observational period. Vaccination significantly reduced the rate of infection and elicited a specific humoral response, which lasted during the whole observational period (9 months). A decay was observed in all considered subgroups. At 35 weeks, workers with no history of pre-vaccine infection showed a significantly lower anti-S titre (-2522 U/mL on average (-2589.7 to -2445.7)); younger workers showed significantly higher anti-S titres (140.2 U/mL on average (82.4 to 201.3)). Only seven immunocompromised workers did not show significant levels of anti-S antibodies; three of them, all females, showed a specific T-cell response. CONCLUSIONS: Comparing the 9-month periods before and after the first vaccine dose, a significant reduction in infection rate was observed (1708 cases vs. 156). Pre-vaccine infection, especially if contracted during the first pandemic wave, greatly enhanced the response to vaccination, which was significantly affected also by age both in extent and duration (inversely related). A gender effect on the T-cell immune response was observed in a small group of workers who did not produce antibodies after vaccine administration.
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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.
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Vacunas contra la COVID-19 , COVID-19 , Anticuerpos Antivirales , COVID-19/prevención & control , Femenino , Personal de Salud , Humanos , Inmunidad , Inmunoglobulina G , Lactante , VacunaciónRESUMEN
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.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Lactante , COVID-19/prevención & control , Anticuerpos , Personal de Salud , ItaliaRESUMEN
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.
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Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Anticuerpos Antivirales , COVID-19/prevención & control , Personal de Salud , Inmunidad , VacunaciónRESUMEN
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.
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BACKGROUND: COVID-19 pandemic is requesting unprecedented efforts by health-care workers (HCWs) in all countries, and especially in Italy during the first semester of 2020. METHODS: This is a retrospective, observational study conducted at the Spedali Civili General Hospital, in Brescia, Northern Italy during the SARS CoV-2 pandemic in the first semester of 2020. Serum samples from HCWs were tested for SARS-CoV-2 spike protein-specific antibodies. An online survey was used to collect demographic, clinical, and epidemiological data. RESULTS: Of the 1893 HCWs included, 433 (22.9%) were found seropositive for SARS-CoV-2 IgG. The cumulative prevalence of SARS-CoV-2 infection (antibodies production or past positive RT-PCR on nasal/throat swab) was 25.1% (475/1893). Fifty-six out of 433 (13%) seropositive participants declared to have been asymptomatic during the study period. The development of COVID-19 signs or symptoms is the main determinant of seropositivity (OR: 11.3, p < 0.0001) along with their duration and severity. 40/290 (14.5%) HCWs with documented positive RT-PCR during the study period did not show any detectable antibody response. IgG levels positively correlate with age, COVID-19-compatible signs and symptoms experienced and their duration. CONCLUSIONS: In this study, carried out in one of the most affected areas in Europe, we demonstrate that most HCWs with COVID-19 related symptoms develop a spike protein-specific antibodies with potential neutralizing effect.