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. 2021 May 13;106(6):1637-1648.
doi: 10.1210/clinem/dgab107.

Dysnatremia is a Predictor for Morbidity and Mortality in Hospitalized Patients with COVID-19

Ploutarchos Tzoulis  1   2 , Julian A Waung  2 , Emmanouil Bagkeris  3 , Ziad Hussein  4   5 , Aiyappa Biddanda  2 , John Cousins  2 , Alice Dewsnip  2 , Kanoyin Falayi  2 , Will McCaughran  2 , Chloe Mullins  2 , Ammara Naeem  2 , Muna Nwokolo  2 , Helen Quah  2 , Syed Bitat  4 , Eithar Deyab  4 , Swarupini Ponnampalam  4 , Pierre-Marc Bouloux  6 , Hugh Montgomery  2   7 , Stephanie E Baldeweg  4   5
Affiliations

Dysnatremia is a Predictor for Morbidity and Mortality in Hospitalized Patients with COVID-19

Ploutarchos Tzoulis et al. J Clin Endocrinol Metab. .

Abstract

Context: Dysnatremia is an independent predictor of mortality in patients with bacterial pneumonia. There is paucity of data about the incidence and prognostic impact of abnormal sodium concentration in patients with coronavirus disease 2019 (COVID-19).

Objective: This work aimed to examine the association of serum sodium during hospitalization with key clinical outcomes, including mortality, need for advanced respiratory support and acute kidney injury (AKI), and to explore the role of serum sodium as a marker of inflammatory response in COVID-19.

Methods: This retrospective longitudinal cohort study, including all adult patients who presented with COVID-19 to 2 hospitals in London over an 8-week period, evaluated the association of dysnatremia (serum sodium < 135 or > 145 mmol/L, hyponatremia, and hypernatremia, respectively) at several time points with inpatient mortality, need for advanced ventilatory support, and AKI.

Results: The study included 488 patients (median age, 68 years). At presentation, 24.6% of patients were hyponatremic, mainly due to hypovolemia, and 5.3% hypernatremic. Hypernatremia 2 days after admission and exposure to hypernatremia at any time point during hospitalization were associated with a 2.34-fold (95% CI, 1.08-5.05; P = .0014) and 3.05-fold (95% CI, 1.69-5.49; P < .0001) increased risk of death, respectively, compared to normonatremia. Hyponatremia at admission was linked with a 2.18-fold increase in the likelihood of needing ventilatory support (95% CI, 1.34-3.45, P = .0011). Hyponatremia was not a risk factor for in-hospital mortality, except for the subgroup of patients with hypovolemic hyponatremia. Sodium values were not associated with the risk for AKI and length of hospital stay.

Conclusion: Abnormal sodium levels during hospitalization are risk factors for poor prognosis, with hypernatremia and hyponatremia being associated with a greater risk of death and respiratory failure, respectively. Serum sodium values could be used for risk stratification in patients with COVID-19.

Keywords: COVID-19; SARS-CoV-2; SIAD; hypernatremia; hyponatremia; sodium.

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Figures

Figure 1.
Figure 1.
Probability of death based on serum sodium values 2 days after admission. Kaplan-Meier curve showing probability of death based on serum sodium status 2 days after admission. Patients with hypernatremia had a 2.34-fold increased risk of death compared to normonatremic patients. **P less than .005.
Figure 2.
Figure 2.
Probability of death based on history of abnormal serum sodium at any time during hospitalization. Kaplan-Meier curve showing probability of death based on exposure to abnormal sodium during hospitalization. Patients with hypernatremia (red) or history both of hypernatremia and hyponatremia (purple) had a 3.05-fold and 2.25-fold increased risk of death compared to normonatremic patients. ***P equals .004. ****P less than .001.
Figure 3.
Figure 3.
The progression of median serum sodium and urea levels during hospital stay. Values are expressed in median (95% CI). Sodium values are colored in black and urea values are colored in pink. The inner bars represent the normal reference ranges for each parameter. Using the Friedman test, the P value was less than .001 for sodium and 0.01 for urea change over the period of hospitalization.
Figure 4.
Figure 4.
Median serum sodium and urea levels during hospitalization in survivors and nonsurvivors. Values are expressed in median (95% CI). Values for survivors are colored in green and for nonsurvivors in red. The blue dotted lines show the upper and the lower reference limit for each parameter. The magnitude of serum sodium increase was larger in nonsurvivors than in survivors. The trajectory of serum urea was similar in survivors and nonsurvivors.
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