ABSTRACT
Introduction Pre exposure prophylaxis with monoclonal antibodies (mAbs) were developed in addition to COVID19 vaccine for immunocompromised and those with insufficient immune response, among them patients with CLL. Omicron variant and its sublineages evolved mutations that escape mAbs neutralizing effect, yet the extent of which was not studied. Methods We evaluated anti-spike titters and neutralization activity of COVID-19 wild type (WT) , Delta , Omicron, BA2, BA4 and BA5 before and after tixagevimab-cilgavimab (TGM/CGM) dose of 150/150mg or 300/300mg in patients with CLL. Results 70 patients were tested 2 weeks before and 4 weeks after receiving TGM/CGM mAbs. After TGM/CGM anti-spike ab level increased 170 folds from 13.6 BAU/ml (IQR, 0.4-288) to 2328 BAU/ml (IQR, 1681-3500). Neutralization activity increased in all variants, and was 176 folds higher in WT and 55 folds higher in Delta compared to 10 folds higher in Omicron and its sublineages (BA2 x11, BA4 x4 , BA5 x18). Over follow-up period of 3 months, 20 patients (29%) with CLL acquired COVID-19 infection, all recovered uneventfully. In a multivariate analysis anti-spike antibody titer was found a significant predictor for post TGM/CGM COVID19 infection. Conclusion Efficacy of preexposure prophylaxis with TGM/CGM in patients with CLL is significantly reduced in era of Omicron and its sublineages BA2, BA4 and BA5.
ABSTRACT
Fatty acid levels in milk vary between day and night milking. Many dairy cows are still kept under white light-emitting diode (W-LED) illumination throughout the night, although it is known to disrupt endogenous circadian rhythms. We investigated the effects of whole-night W-LED illumination (125 lux) on milk yield and circadian composition, compared to a natural light−dark (LD) cycle of 10 h light. Mid−late lactation cows (n = 34) that were exposed to natural LD cycle showed circadian variation in milk fat composition, characterized by higher health-promoting monounsaturated fatty acid (MUFA; 24.2 ± 0.4 vs. 23.2 ± 0.4 g/100 g fat, p < 0.001) and lower saturated fatty acid levels (71.2 ± 0.4 vs. 72.5 ± 0.4, p < 0.001) at 13:30 h (day milk) than at 03:30 h (night milk). Compared to natural LD (n = 16), W-LED (n = 18) did not affect milk production or milk fat yields, yet abolished the milking time variation in milk fat composition towards a less healthy fatty acid profile. This lowered MUFA levels of day milk (23.8 ± 0.4 vs. 26.7 ± 0.4, p < 0.01). Therefore, W-LED has no commercial advantage over the tested natural LD cycle, and conversely, even shows circadian disruption. Accordingly, a natural LD cycle of 10 h light is preferable over W-LED from the perspective of cost savings, the cows' well-being, and preserving the natural milk fat profile, as the nutritional value of the day milk is slightly higher.
