ABSTRACT
OBJECTIVE: To compare patients with DKA, hyperglycaemic hyperosmolar syndrome (HHS), or mixed DKA-HHS and COVID-19 [COVID (+)] to COVID-19-negative (-) [COVID (-)] patients with DKA/HHS from a low-income, racially/ethnically diverse catchment area. METHODS: A cross-sectional study was conducted with patients admitted to an urban academic medical center between 1 March and 30 July 2020. Eligible patients met lab criteria for either DKA or HHS. Mixed DKA-HHS was defined as meeting all criteria for either DKA or HHS with at least 1 criterion for the other diagnosis. RESULTS: A total of 82 participants were stratified by COVID-19 status and type of hyperglycaemic crisis [26 COVID (+) and 56 COVID (-)]. A majority were either Black or Hispanic. Compared with COVID (-) patients, COVID (+) patients were older, more Hispanic and more likely to have type 2 diabetes (T2D, 73% vs 48%, p < .01). COVID(+) patients had a higher mean pH (7.25 ± 0.10 vs 7.16 ± 0.16, p < .01) and lower anion gap (18.7 ± 5.7 vs 22.7 ± 6.9, p = .01) than COVID (-) patients. COVID (+) patients were given less intravenous fluids in the first 24 h (2.8 ± 1.9 vs 4.2 ± 2.4 L, p = .01) and were more likely to receive glucocorticoids (95% vs. 11%, p < .01). COVID (+) patients may have taken longer to resolve their hyperglycaemic crisis (53.3 ± 64.8 vs 28.8 ± 27.5 h, p = .09) and may have experienced more hypoglycaemia <3.9 mmol/L (35% vs 19%, p = .09). COVID (+) patients had a higher length of hospital stay (LOS, 14.8 ± 14.9 vs 6.5 ± 6.0 days, p = .01) and in-hospital mortality (27% vs 7%, p = .02). DISCUSSION: Compared with COVID (-) patients, COVID (+) patients with DKA/HHS are more likely to have T2D. Despite less severe metabolic acidosis, COVID (+) patients may require more time to resolve the hyperglycaemic crisis and experience more hypoglycaemia while suffering greater LOS and risk of mortality. Larger studies are needed to examine whether differences in management between COVID (+) and (-) patients affect outcomes with DKA/HHS.
Subject(s)
COVID-19/complications , Diabetic Ketoacidosis/complications , Hyperglycemic Hyperosmolar Nonketotic Coma/complications , Acid-Base Equilibrium , Adult , Age Factors , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , Comorbidity , Cross-Sectional Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetic Ketoacidosis/blood , Female , Fluid Therapy , Glucocorticoids/therapeutic use , Humans , Hydrogen-Ion Concentration , Hyperglycemic Hyperosmolar Nonketotic Coma/blood , Length of Stay , Male , Middle Aged , SARS-CoV-2 , Safety-net ProvidersABSTRACT
The signal processing capabilities of bacterial signaling networks offer immense potential for advanced phospho-signaling systems for synthetic biology. Emerging models suggest that complex development may require interconnections between what were once thought to be isolated signaling arrays. For example, Caulobacter crescentus achieves the feat of asymmetric division by utilizing a novel pseudokinase DivL, which senses the output of one signaling pathway to modulate a second pathway. It has been proposed that DivL reverses signal flow by exploiting conserved kinase conformational changes and protein-protein interactions. We engineered a series of DivL-based modulators to synthetically stimulate reverse signaling of the network in vivo. Stimulation of conformational changes through the DivL signal transmission helix resulted in changes to hallmark features of the network: C. crescentus motility and DivL accumulation at the cell poles. Additionally, mutations to a conserved PAS sensor transmission motif disrupted reverse signaling flow in vivo. We propose that synthetic stimulation and sensor disruption provide strategies to define signaling circuit organization principles for the rational design and validation of synthetic pathways.