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.

Placental metal concentrations and birth outcomes: The Environment and Childhood (INMA) project.

OBJECTIVE: To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain. METHODS: Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneously. Effect modification by sex was also evaluated. RESULTS: Elevated placental Cd levels (>5.79 vs. <3.30 ng/g) were associated with reduced birth weight (-111.8 g, 95%CI = -215.6; -8.06, p-trend = 0.01) and length (-0.62 cm, 95%CI = -1.20; -0.04, p-trend = 0.02), while a 10% increase in Cd was associated with 1.21-fold increased odds (95%CI = 1.01; 1.43) of LBW in the global sample but with 14% lower odds (95%CI = 0.78; 0.96) of preterm delivery in males (Pinteraction = 0.10). Detected (vs. undetected) Hg was associated with reduced head circumference (-0.49 cm, 95%CI = -1.00; 0.03) in females (Pinteraction = 0.03). A 10% increase in placental Mn was associated with slight increases in gestational age (0.04 weeks, 95%CI = 0.01; 0.07) in the global sample and in head circumference (0.05 cm, 95%CI = -0.01; 0.10) in females (Pinteraction = 0.03). Elevated Cr levels (>99.6 vs. <56.1 ng/g) were associated with reduced birth length (-0.68 cm, 95%CI = -1.33; -0.04, p-trend = 0.02) and slightly increased gestational age (0.35 weeks, 95%CI = -0.07; 0.77, p-trend = 0.08) in the global sample. As and Pb were detected in few placentas (27% and 13%, respectively) and were not associated with any studied birth outcome. CONCLUSIONS: Data suggest that in utero exposure to Cd, Hg, and Cr could adversely affect fetal growth, whereas Mn and Cr appear to have a positive effect on gestational age. Given the relatively small number of subjects, sex-specific associations should be interpreted with caution.