What is the aetiology of dysnatraemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, retrospective observational study in 11 Dutch hospitals

Abstract

Objectives: To evaluate the relationship among dysnatraemia at hospital presentation and duration of admission, risk of intensive care unit (ICU) admission and all-cause mortality and to assess the underlying pathophysiological mechanism of hyponatraemia in patients with COVID-19. Our hypothesis is that both hyponatraemia and hypernatraemia at presentation are associated with adverse outcomes.

Design: Observational study.

Setting: Secondary care; 11 Dutch hospitals (2 university and 9 general hospitals).

Participants: An analysis was performed within the retrospective multicentre cohort study COVIDPredict. 7811 patients were included (60% men, 40% women) between 24 February 2020 and 9 August 2022. Patients who were ≥18 years with PCR-confirmed COVID-19 or CT with COVID-19 reporting and data system score≥4 and alternative diagnosis were included. Patients were excluded when serum sodium levels at presentation were not registered in the database or when they had been transferred from another participating hospital.

Outcome measures: We studied demographics, medical history, symptoms and outcomes. Patients were stratified according to serum sodium concentration and urinary sodium excretion.

Results: Hyponatraemia was present in 2677 (34.2%) patients and hypernatraemia in 126 (1.6%) patients. Patients with hyponatraemia presented more frequently with diarrhoea, lower blood pressure and tachycardia. Hyponatraemia was, despite a higher risk for ICU admission (OR 1.27 (1.11-1.46; p<0.001)), not associated with mortality or the risk for intubation. Patients with hypernatraemia had higher mortality rates (OR 2.25 (1.49-3.41; p<0.001)) and were at risk for ICU admission (OR 2.89 (1.83-4.58)) and intubation (OR 2.95 (1.83-4.74)).

Conclusions: Hypernatraemia at presentation was associated with adverse outcomes in patients with COVID-19. Hypovolaemic hyponatraemia was found to be the most common aetiology of hyponatraemia. Hyponatraemia of unknown aetiology was associated with a higher risk for ICU admission and intubation and longer duration of admission.

Keywords: COVID-19; infectious diseases; internal medicine.

Figure 1

HRs of Cox proportional survival curves for survival probability for each sodium value adjusted for age, sex assigned at birth, a history of chronic kidney disease and a history of hypertension. The grey area indicates the normonatremia. Table shows HRs for covariates and sodium as a continuous variable (A). Cox proportional survival curves at the mean of covariates for (B) unadjusted 6-week mortality stratified by normonatremia, hyponatraemia and hypernatraemia, (C) 6-week mortality adjusted for age, sex assigned at birth, a history of chronic kidney disease and a history of hypertension stratified in normonatremia, hyponatraemia and hypernatraemia, (D) unadjusted 6-week mortality stratified by aetiology. **Indicates a p value<0.01. ***Indicates a p value<0.001.

Figure 2

OR for adverse outcomes (death/palliative discharge (A), intensive care unit admission (B), invasive ventilation (C)) for each SARS-CoV-2 variant compared with patients in that started having symptoms when the initial variants for patients with hyponatraemia, hypernatraemia or normonatremia at admission. ***Indicates a p value<0.001 for the OR as calculated by binary logistic regression. (D) Incidence of hyponatraemia, normonatremia and hypernatraemia for each variant, *Indicates a p value<0.05 as compared with the first quartile for the χ² statistic with Bonferroni post hoc correction.