Control of COVID-19 Outbreaks under Stochastic Community Dynamics, Bimodality, or Limited Vaccination.

Reaching population immunity against COVID-19 is proving difficult even in countries with high vaccination levels. Thus, it is critical to identify limits of control and effective measures against future outbreaks. The effects of nonpharmaceutical interventions (NPIs) and vaccination strategies are analyzed with a detailed community-specific agent-based model (ABM). The authors demonstrate that the threshold for population immunity is not a unique number, but depends on the vaccination strategy. Prioritizing highly interactive people diminishes the risk for an infection wave, while prioritizing the elderly minimizes fatalities when vaccinations are low. Control over COVID-19 outbreaks requires adaptive combination of NPIs and targeted vaccination, exemplified for Germany for January-September 2021. Bimodality emerges from the heterogeneity and stochasticity of community-specific human-human interactions and infection networks, which can render the effects of limited NPIs uncertain. The authors' simulation platform can process and analyze dynamic COVID-19 epidemiological situations in diverse communities worldwide to predict pathways to population immunity even with limited vaccination.

Acute hypothalamo-pituitary-adrenal axis response to LPS-induced endotoxemia: expression pattern of kinin type B1 and B2 receptors.

Bradykinin (BK) and des-Arg9-BK are pro-inflammatory mediators acting via B2 (B2R) and B1 (B1R) receptors, respectively. We investigated the role of B2R and B1R in lipopolysaccharide (LPS)-induced hypothalamo-pituitary-adrenal (HPA) axis activation in SD rats. LPS given intraperitoneally (ip) up-regulated B1R mRNA in the hypothalamus, both B1R and B2R were up-regulated in pituitary and adrenal glands. Receptor localization was performed using immunofluorescence staining. B1R was localized in the endothelial cells, nucleus supraopticus (SON), adenohypophysis and adrenal cortex. B2R was localized nucleus paraventricularis (PVN) and SON, pituitary and adrenal medulla. Blockade of B1R prior to LPS further increased ACTH release and blockade of B1R 1 h after LPS decreased its release. In addition, we evaluated if blockade of central kinin receptors influence the LPS-induced stimulation of hypothalamic neurons. Blockade of both B1R and B2R reduced the LPS-induced c-Fos immunoreactivity in the hypothalamus. Our data demonstrate that a single injection of LPS induced a differential expression pattern of kinin B1R and B2R in the HPA axis. The tissue specific cellular localization of these receptors indicates that they may play a crucial role in the maintenance of body homeostasis during endotoxemia.