ABSTRACT
Data from human and animal studies are highly suggestive of an influence of time of day of vaccine administration on host immune responses. In this population-based study, we aimed to investigate the effect of time of day of administration of a COVID-19 vector vaccine, ChAdOx1 nCoV-19 (AstraZeneca), on SARS-CoV-2 anti-spike S1 immunoglobulin (IgG) levels. Participants were 803 university employees who received their first vaccine dose in March 2021, had serology data at baseline and at 3 weeks, and were seronegative at baseline. Antibody levels were determined in binding antibody units (BAU/mL) using enzyme-linked immunosorbent assay (ELISA). Generalized additive models (GAM) and linear regression were used to evaluate the association of time of day of vaccination continuously and in hourly bins with antibody levels at 3 weeks. Participants had a mean age of 42 years (SD: 12; range: 21-74) and 60% were female. Time of day of vaccination was associated non-linearly ("reverse J-shape") with antibody levels. Morning vaccination was associated with the highest (9:00-10:00 h: mean 292.1 BAU/mL; SD: 262.1), early afternoon vaccination with the lowest (12:00-13:00 h: mean 217.3 BAU/mL; SD: 153.6), and late afternoon vaccination with intermediate (14:00-15:00 h: mean 280.7 BAU/mL; SD: 262.4) antibody levels. Antibody levels induced by 12:00-13:00 h vaccination (but not other time intervals) were significantly lower compared to 9:00-10:00 h vaccination after adjusting for potential confounders (beta coefficient = -75.8, 95% confidence interval [CI] = -131.3, -20.4). Our findings show that time of day of vaccination against SARS-CoV-2 has an impact on the magnitude of IgG antibody levels at 3 weeks. Whether this difference persists after booster vaccine doses and whether it influences the level of protection against COVID-19 needs further evaluation.
ABSTRACT
OBJECTIVE: We analyzed the annual prevalence of onset-DKA (diabetic ketoacidosis) from 2012 to 2020 with a sub-analysis for lockdown-periods during the COVID-19 pandemic in 2020. DESIGN: All newly diagnosed children with type 1 diabetes (T1D) aged <15 years are prospectively registered in the population-based Austrian Diabetes Incidence Study in Austria. MAIN OUTCOME MEASURES: The annual DKA prevalence was analyzed using Joinpoint regression. Definition of DKA: pH <7.3, mild DKA: pH 7.3 to ≤ 7.1, severe DKA: pH <7.1. DKA prevalence during the lockdown periods in 2020 and the corresponding periods in 2015-2019 were examined using Fisher's exact test. RESULTS: In the years 2012-2020 the mean prevalence for onset-DKA in Austria was 43.6% [95%CI (confidence interval): 41.6, 45.7] and thus above the mean prevalence of previous decades (1989-2011) of 37,1 % (95%CI: 35.6, 38.6). A particularly high prevalence was found among children <2 years of age (72.0% DKA, 32.8% severe DKA). No significant gender difference was found. Prevalence of severe DKA at T1D-onset increased significantly since 2015 (p = 0.023). During the lockdown in 2020, 59.3% of children were diagnosed with DKA at T1D-onset, compared to 42.1% during the previous 5 years (p = 0.022). Moreover, 20% of children had severe DKA at T1D diagnosis, compared to 14% during the comparison period. CONCLUSIONS: The previously already high prevalence of DKA at T1D-onset has further increased over time. The COVID-19 pandemic has exacerbated the problem of a late or delayed diagnosis of diabetes in children resulting in onset-DKA. The alarmingly increased prevalence of DKA in Austrian children with T1D calls for urgent action.