Hyponatremia is common in COVID-19’s patients and associated with biological risk factors of poor outcome.
According to natremia at admission, two groups of patients were isolated: hyponatremic (natremia < 135 mM, n = 101, 31% of the cohort) and normonatremic (natremia ≥ 135 mM, n = 222) patients. Six patients with hypernatremia were excluded. Hyponatremia was generally mild (mean of natremia in the hyponatremic group 132.3 mM ± 1.7 [123–134]). Only 12 patients had a natremia below 130 mM. 30 on 101 hyponatremic patients (30%) had natremia measurement in the same laboratory during the year preceding COVID-19 and only 10 were found previously hyponatremic.
Plasmatic osmolality was rarely measured in our non-interventional retrospective cohort of mild hyponatremia (12 patients), and mostly after intravenous fluid administration. Thus, we unfortunately did not have consistent plasmatic osmolality data. To note, only 3 out of 12 samples were below 280-mOsm/ kg/H2O. On 34 urinary sodium measurements at admission in the hyponatremic patients, 15 (44%) had a < 30 mM natriuresis, which may suggest an extracellular dehydration state. Systolic blood pressure at admission and digestive symptoms (diarrhea, vomiting) were not significantly different between hyponatremic and normonatremic groups (Table 1). Neurologic symptoms (headache, confusion) previously described in COVID (11,12) were also not significantly different between groups at admission (Table 1).
Age and time between symptoms and hospital admission were similar between hyponatremic and normonatremic patients (Table 1). There were significantly more male patients in the hyponatremic group (p = 0.005). The major comorbidities classically associated with hyponatremia (cirrhosis, active neoplasia), and obesity were not different between groups. Surprisingly, more patients in the normonatremic group had a history of congestive heart failure (p = 0.031) (Table 1).
We looked for available prognostic factors in our cohort. Temperature at admission was significantly higher in hyponatremic patients (p < 0.001). Respectively 58 out of 93 (62%) patients and 83 out of 193 (43%) had a temperature above 38.5 °C in hyponatremic and normonatremic patients (Pearson Chi-squared test p = 0.003), which indicates a strong and significant correlation between high temperature and hyponatremia. At admission, serum creatinine and lymphocytes counts, were similar between the two groups (Table 2). C-Reactive protein was significantly higher in hyponatremic patients (p = 0.04) with a non-negligible number of missing values (32% in hyponatremic versus 22% in normonatremic group) (Table 2). AST and ALT were also significantly higher in hyponatremic patients (respectively p = 0.001 and 0.03) (Table 2).
Hyponatremia in COVID-19 is significantly associated with a poor outcome.
ICU admission, mechanic ventilation or death, were significantly higher in hyponatremic compared to normonatremic patients (respectively 34 versus 14%; p < 0.001; 16% versus 5%; p = 0.002; 19 versus 9%, p = 0.021) (Table 1).
We performed a multivariate analysis with available variables of interest (known as prognostic factor and/or with a p value < 0.2 in univariate analysis in the association with the primary outcome): age, sex, tympanic temperature, diabetes, serum creatinine, ALT, lymphocytes count and oxygen flow rate at admission (Table 3). Due to significant correlation with ALT associated with more missing values, AST was not included in the model. Respiratory rate and oxygen flow rate divided in three categories (none, ≤ 6 l/min, > 6 l/min) were also strongly associated (Kruskal Wallis test, p = 8.5e-09). Moreover, respiratory rate was not available in 61 patients (19% of the cohort). Thus, this parameter was not included, as we could not exclude that a missing value suggest an evaluation of lower severity at the admission of the patient. In multivariate analysis, hyponatremia at admission was an independent predictor of poor outcome (adjusted Odds-ratio: 2.49 [1.18–5.33, p = 0.017]) such as an oxygen flow rate above 6 l/min (adjusted Odds-ratio: 18.83 [6.32–64.30, p < 0.001]) (Table 3). Tympanic temperature, significantly higher in hyponatremic group was not an independent predictor of poor outcome in our cohort (adjusted Odds-ratio: 2.07 [0.96–4.58, p = 0.065] (Table 3).
Hyponatremia in SARS-CoV-2 infection may reflect severity of pulmonary lesions
As hyponatremia had already been described as a prognostic factor in SARS pulmonary infection and pneumonia (13), we assessed if hyponatremia was the consequence of severe pulmonary lesions in COVID-19. Oxygen flow at admission was not different between hyponatremic and normonatremic patients (Table 1). Mean oxygen flow rate in the patients with moderate oxygen flow rate (≤ 6 l/min) were also not significantly different (Table 1). We compared pulmonary lesions between hyponatremic and normonatremic patients (Table 2). 147 patients of our cohort had a pulmonary assessment with a CT-scanner. Pulmonary lesions on the first thoracic CT-scanner performed during the hospitalization were significantly more extended in the hyponatremic compared to the normonatremic group (Pearson Chi-squared test, p = 0.03) (Table 2) and extension of the lesions above 50% of the lungs was associated with poor outcome in univariate analysis (Odds-Ratio 18.86 [6.65–60.74, p < 0.001]) (Table 3).