ABSTRACT
We report for the first time therapy-resistant hypernatremia (plasma sodium concentration ≥150 mmol per liter) developing in 6 of 12 critically ill coronavirus disease 2019 (COVID-19) patients age 57-84 years requiring mechanical ventilation. There was no correlation between plasma sodium concentrations and sodium input. Plasma concentrations of chloride were elevated, those of potassium decreased. These findings are consistent with abnormally increased renal sodium reabsorption, possibly caused by increased angiotensin II activity secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced downregulation of angiotensin-converting enzyme 2 (ACE2) receptors. As hypernatremia was associated with increased length of intensive care unit stay, special attention should be paid to the electrolyte status of COVID-19 patients.
Subject(s)
Coronavirus Infections/complications , Fluid Therapy/methods , Hypernatremia/complications , Natriuretic Agents/therapeutic use , Pneumonia, Viral/complications , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Case-Control Studies , Chlorides/blood , Cohort Studies , Coronavirus Infections/blood , Female , Fluid Therapy/statistics & numerical data , Hospital Mortality , Humans , Hypernatremia/blood , Hypernatremia/epidemiology , Hypernatremia/therapy , Length of Stay/statistics & numerical data , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Renal Dialysis , Respiration, Artificial , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2ABSTRACT
Patterning of vertebrate melanophores is essential for mate selection and protection from UV-induced damage. Patterning can be influenced by circulating long-range factors, such as hormones, but it is unclear how their activity is controlled in recipient cells to prevent excesses in cell number and migration. The zebrafish wanderlust mutant harbors a mutation in the sheddase bace2 and exhibits hyperdendritic and hyperproliferative melanophores that localize to aberrant sites. We performed a chemical screen to identify suppressors of the wanderlust phenotype and found that inhibition of insulin/PI3Kγ/mTOR signaling rescues the defect. In normal physiology, Bace2 cleaves the insulin receptor, whereas its loss results in hyperactive insulin/PI3K/mTOR signaling. Insulin B, an isoform enriched in the head, drives the melanophore defect. These results suggest that insulin signaling is negatively regulated by melanophore-specific expression of a sheddase, highlighting how long-distance factors can be regulated in a cell-type-specific manner.
