Objective: The pandemic of coronavirus disease (COVID-19) has rapidly spread globally and infected millions of people. The prevalence and prognostic impact of dysnatremia in COVID-19 is inconclusive. Therefore, we investigated the prevalence and outcome of dysnatremia in COVID-19. Design: The prospective, observational, cohort study included consecutive patients with clinical suspicion of COVID-19 triaged to a Swiss Emergency Department between March and July 2020. Methods: Collected data included clinical, laboratory and disease severity scoring parameters on admission. COVID-19 cases were identified based on a positive nasopharyngeal swab test for SARS-CoV-2, patients with a negative swab test served as controls. The primary analysis was to assess the prognostic impact of dysnatremia on 30-day mortality using a cox proportional hazard model. Results: 172 (17%) cases with COVID-19 and 849 (83%) controls were included. Patients with COVID-19 showed a higher prevalence of hyponatremia compared to controls (28.1% vs. 17.5%, p<0.001); while comparable for hypernatremia (2.9% vs 2.1%, p=0.34). In COVID-19 but not in controls, hyponatremia was associated with a higher 30-day mortality (HR 1.4, 95%-CI 1.10-16.62, p=0.05). In both groups, hypernatremia on admission was associated with higher 30-day mortality (COVID-19: HR 11.5, 95%-CI 5.00-26.43, p<0.001; controls: HR 5.3, 95%-CI 1.60-17.64, p=0.006). In both groups, hyponatremia and hypernatremia were significantly associated with adverse outcome, e.g. intensive care unit admission, longer hospitalization, and mechanical ventilation. Conclusion: Our results underline the importance of dysnatremia as predictive marker in COVID-19. Treating physicians should be aware and appropriate treatment measures taken in patients with COVID-19 and dysnatremia.

BACKGROUND The differential diagnosis of diabetes insipidus is challenging. The most reliable approaches are copeptin measurements after hypertonic saline infusion or arginine, which is a known growth hormone secretagogue but has recently also been shown to stimulate the neurohypophysis. Similar to arginine, glucagon stimulates growth hormone release, but its effect on the neurohypophysis is poorly studied. DESIGN Double-blind, randomized, placebo-controlled trial including 22 healthy participants, 10 patients with central diabetes insipidus, and 10 patients with primary polydipsia at the University Hospital Basel, Switzerland. METHODS Each participant underwent the glucagon test (subcutaneous injection of 1mg glucagon), and placebo test. The primary objective was to determine whether glucagon stimulates copeptin and to explore whether the copeptin response differentiates between diabetes insipidus and primary polydipsia. Copeptin levels were measured at baseline and 30, 60, 90, 120, 150, 180minutes after injection. RESULTS In healthy participants, glucagon stimulated copeptin with a median increase of 7.56 (2.38; 28.03) pmol/l, while placebo had no effect (0.10pmol/l (-0.70; 0.68); p<0.001). In patients with diabetes insipidus, copeptin showed no relevant increase upon glucagon, with an increase of 0.55 (0.21; 1.65) pmol/l, whereas copeptin was stimulated in patients with primary polydipsia with an increase of 15.70 (5.99; 24.39)pmol/l. Using a copeptin cutoff level of 4.6pmol/l had a sensitivity of 100% (95%CI 100-100) and a specificity of 90% (95%CI 70-100) to discriminate between diabetes insipidus and primary polydipsia. CONCLUSION Glucagon stimulates the neurohypophysis, and glucagon-stimulated copeptin has the potential for a safe, novel, and precise test in the differential diagnosis of diabetes insipidus.

No abstract