Use of chlorhexidine to eradicate oropharyngeal SARS-CoV-2 in COVID-19 patients.

As public distribution of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is underway, prevention of coronavirus disease 2019 (COVID-19) relies on minimizing spread. In this study, chlorhexidine gluconate was investigated as a topical antimicrobial agent against SARS-CoV-2. This was a randomized, prospective cohort study using chlorhexidine as an oral rinse and posterior oropharyngeal spray in hospitalized COVID-19 patients. The primary outcome was presence or absence of laboratory-confirmed SARS-CoV-2 in the oral and oropharyngeal cavities after 4 days of chlorhexidine use and standard of care (study group) or standard of care only (control group). SARS-CoV-2 was eliminated from the oropharynx in 62.1% of patients who used chlorhexidine as an oral rinse, versus 5.5% of the control group patients. Among patients who used a combination of oral rinse and oropharyngeal spray, 86.0% eliminated oropharyngeal SARS-CoV-2, versus 6.3% of control patients. Chlorhexidine is a simple and safe addition to current COVID-19 prevention guidelines and may play a significant role in reducing disease spread.

Glycogen Repletion in Brown Adipose Tissue upon Refeeding Is Primarily Driven by Phosphorylation-Independent Mechanisms.

Glycogen storage in brown adipose tissue (BAT) is generally thought to take place through passive, substrate-driven activation of glycogenesis rather than programmatic shifts favoring or opposing the storage and/or retention of glycogen. This perception exists despite a growing body of evidence suggesting that BAT glycogen storage is actively regulated by covalent modification of key glycogen-metabolic enzymes, protein turnover, and endocrine hormone signaling. Members of one such class of covalent-modification regulators, glycogen-binding Phosphoprotein Phosphatase-1 (PP1)-regulatory subunits (PPP1Rs), targeting PP1 to glycogen-metabolic enzymes, were dynamically regulated in response to 24 hr of starvation and/or 24 hr of starvation followed by ad libitum refeeding. Over-expression of the PPP1R Protein Targeting to Glycogen (PTG), under the control of the aP2 promoter in mice, inactivated glycogen phosphorylase (GP) and enhanced basal- and starvation-state glycogen storage. Total interscapular BAT glycogen synthase and the constitutive activity of GS were conditionally affected. During starvation, glucose-6-phosphate (G-6-P) levels and the relative phosphorylation of Akt (p-Ser-473-Akt) were both increased in PTG-overexpressing (Tg) mice, suggesting that elevated glycogen storage during starvation modifies broader cellular metabolic pathways. During refeeding, Tg and WT mice reaccumulated glycogen similarly despite altered GS and GP activities. All observations during refeeding suggest that the phosphorylation states of GS and GP are not physiologically rate-controlling, despite there being a clear balance of endogenous kinase- and phosphatase activities. The studies presented here reveal IBAT glycogen storage to be a tightly-regulated process at all levels, with potential effects on nutrient sensing in vivo.