Relaxing restrictions at the pace of vaccination increases freedom and guards against further COVID-19 waves.

Mass vaccination offers a promising exit strategy for the COVID-19 pandemic. However, as vaccination progresses, demands to lift restrictions increase, despite most of the population remaining susceptible. Using our age-stratified SEIRD-ICU compartmental model and curated epidemiological and vaccination data, we quantified the rate (relative to vaccination progress) at which countries can lift non-pharmaceutical interventions without overwhelming their healthcare systems. We analyzed scenarios ranging from immediately lifting restrictions (accepting high mortality and morbidity) to reducing case numbers to a level where test-trace-and-isolate (TTI) programs efficiently compensate for local spreading events. In general, the age-dependent vaccination roll-out implies a transient decrease of more than ten years in the average age of ICU patients and deceased. The pace of vaccination determines the speed of lifting restrictions; Taking the European Union (EU) as an example case, all considered scenarios allow for steadily increasing contacts starting in May 2021 and relaxing most restrictions by autumn 2021. Throughout summer 2021, only mild contact restrictions will remain necessary. However, only high vaccine uptake can prevent further severe waves. Across EU countries, seroprevalence impacts the long-term success of vaccination campaigns more strongly than age demographics. In addition, we highlight the need for preventive measures to reduce contagion in school settings throughout the year 2021, where children might be drivers of contagion because of them remaining susceptible. Strategies that maintain low case numbers, instead of high ones, reduce infections and deaths by factors of eleven and five, respectively. In general, policies with low case numbers significantly benefit from vaccination, as the overall reduction in susceptibility will further diminish viral spread. Keeping case numbers low is the safest long-term strategy because it considerably reduces mortality and morbidity and offers better preparedness against emerging escape or more contagious virus variants while still allowing for higher contact numbers (freedom) with progressing vaccinations.

Peripheral thyroid hormone levels and hepatic thyroid hormone deiodinase gene expression in dairy heifers on the day of ovulation and during the early peri-implantation period.

BACKGROUND: Before the onset of fetal thyroid hormone production, the transplacental delivery of maternal thyroid hormones is necessary for embryonic and fetal development. Therefore, the adaptation of maternal thyroid hormone metabolism may be important for pregnancy success and embryo survival. The aims of this study were to determine the thyroid hormone levels during the early peri-implantation period until day 18 and on the day of ovulation, to determine whether pregnancy success is dependent on a "normothyroid status" and to determine whether physiological adaptations in maternal thyroid hormone metabolism occur, which may be necessary to provide sufficient amounts of biologically active T3 to support early pregnancy. Therefore, blood samples obtained on the day of ovulation (day 0) and days 14 and 18 of the Holstein-Friesian heifers (n = 10) during the respective pregnant, non-pregnant and negative control cycles were analyzed for thyroid-stimulating-hormone (TSH), thyroxine (T4) and triiodothyronine (T3). Liver biopsies (day 18) from pregnant and respective non-pregnant heifers were analyzed for mRNA expression of the most abundant hepatic thyroid hormone deiodinase (DIO1) by real time qPCR. RESULTS: Although liver DIO1 mRNA expression did not differ between the pregnant and non-pregnant heifers on day 18, the serum concentrations of TSH and T3 on day 18 were higher in non-pregnant heifers compared to pregnant heifers (P < 0.05). Moreover, T3 decreased between day 0 and 18 in pregnant heifers (P < 0.001). CONCLUSIONS: In conclusion, no associations between thyroid hormone patterns on day 18 and pregnancy success were detected. During the early peri-implantation period, TSH and T3 may be affected by the pregnancy status because both TSH and T3 were lower on day 18 in pregnant heifers compared to non-pregnant dairy heifers. In further studies, the thyroid hormone axis should be evaluated throughout the entire gestation to confirm these data and identify other possible effects of pregnancy on the thyroid hormone axis in cattle.

Serum IGFBP4 concentration decreased in dairy heifers towards day 18 of pregnancy.

This study was conducted to determine if the main components of the somatotropic axis change during the early phase of pregnancy in the maternal blood system and whether differences exist on day 18 after pregnancy recognition by the maternal organism. Blood samples of pregnant heifers (Holstein Friesian; n = 10 after embryo transfer) were obtained on the day of ovulation (day 0), as well as on days 7, 14, 16 and 18 and during pregnant, non-pregnant and negative control cycles. The concentrations of progesterone (P4), oestrogen, growth hormone (GH), insulin-like growth factor-1 and -2 (IGF1, -2) and IGF-binding protein-2, -3 and -4 (IGFBP2, -3, -4) were measured. The mRNA expressions of growth hormone receptor 1A, IGF1, IGF2, IGFBP2, IGFBP3 and IGFBP4 were detected using RT-qPCR in liver biopsy specimens (day 18). In all groups, total serum IGF1 decreased from day 0 to 16. Notably, IGFBP4 maternal blood concentrations were lower during pregnancy than during non-pregnant cycles and synchronized control cycles. It can be speculated that the lower IGFBP4 in maternal blood may result in an increase of free IGF1 for local action. Further studies regarding IGFBP4 concentration and healthy early pregnancy are warranted.