Dysnatremia is associated with increased mortality in patients with pneumonia caused by COVID-19 [8]. In the present study, hypernatremia was associated with a 50% higher risk of mortality in multivariate analysis in patients admitted by COVID-19. We evaluated 1,000 patients hospitalized with COVID-19 and detected that hypernatremia was largely frequent, affecting 76.1% of individuals who died. Our results are consistent with those of other relevant investigations to date [7,13–15,21].
The sodium levels disturbance is the most common electrolyte abnormality in clinical practice. Clinical data reported that hypernatremia is present in approximately 2.0% of patients older than 65 years but in almost 4.8% of those older than 75 years admitted to the hospital [22]. In a retrospective study involving 8,441 older patients admitted to the ICU, approximately 3.6% had hypernatremia on admission, and 15.3% developed hypernatremia during hospitalization; the mortality rate in those admitted with hypernatremia was approximately 33.3%, while patients without hypernatremia had a mortality rate of 18.1% [23].
In a previous study that evaluated 111,545 sodium measures, hypernatremic and hyponatremic patients showed higher LOS than eunatremic. The mortality rates of hyponatremic and hypernatremic inpatients were 19% and 48%, respectively. Disease severity as measured by LOS and mortality indicated these critical limits should not be broadened [24]. Hypernatremia has detrimental effects on various physiologic functions and was shown to be an independent risk factor for increased mortality in COVID-19 patients [25]. These results are in agreement with our findings, where hypernatremia and older age were associated with mortality by COVID-19.
Additionally, longer LOS, older age, and kidney disease were significant predictors for death. The association between hypernatremia, kidney disease, and higher LOS with mortality by COVID-19 was previously shown in a previous multicentric cohort that evaluated 4,664 patients [8]. These associations were observed in the present study, allowing a clinical characterization of COVID-19 patients in southern Brazil, reproducing the findings of risk factors for mortality. On the other hand, hyponatremia could indicate pulmonary involvement, whereas hypernatremia is associated with prolonged LOS and the need for intensive care/mechanical ventilation, particularly when resulting from prior hyponatremia [14].
In this COVID-19 cohort, hypernatremia and kidney disease were associated independently with mortality. Previous studies showed that is indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have pivotal effects on hypertension control, proteinuria, immunosuppressant therapy, the efficacy of antiproteinuric pharmacologic therapy, and maintaining an optimal volume status. Dietary sodium intake is an important factor in patients with all stages of chronic kidney disease, counting those receiving dialysis therapy or those who have received a kidney transplant [25–28].
Many studies confirmed that both dysnatremia were independently associated with poor prognosis in patients hospitalized by COVID-19 [7,8,28,29]. Interestingly, in patients hospitalized with COVID-19, was detected that admittance hyponatremia was frequent; affecting more than 20% of patients, for a total of 957 subjects, and hypernatremia was found in only 3.7%, a total of 174 subjects [8]. Another study, including 488 subjects with COVID-19, found an incidence of 24.6% of hyponatremia and 5.3% of hypernatremia [13]. Also, hypernatremia detected two days after admission and exposure to hypernatremia at any time point during hospitalization were associated with a 2.34-fold and 3.05-fold increased risk of death, respectively, compared to eunatremia. Hyponatremia at admission was linked with a 2.18-fold increase in the likelihood of needing ventilatory support [13]. These results showed the pivotal importance of sodium measures in patients hospitalized, including COVID-19 patients, mainly in ICU patients.
This study has important limitations. This is a retrospective study and the consequential relationship between dysnatremia and mortality cannot be asserted. It is also not possible to assess the effect of hypernatremia treatment on the prognosis. Finally, the serum sodium was not corrected for glycemia. The main advantage of the study is a large number of patients were included, all of whom were admitted with RT-PCR-confirmed COVID-19. Also, all patients were followed-up throughout the entire period of hospitalization. In addition, all sodium measurements during follow-up were considered, computing the highest and lowest sodium values. In this sense, the stratification of patients on arrival at the hospital (considering clinical and laboratory tests, for example) makes it possible to identify those who are at greater risk of an unfavorable clinical outcome and makes it possible to improve monitoring and availability of resources for them [1,28].
In conclusion, hypernatremia during hospitalization is an important risk factor for poor prognosis, being associated independently with a greater risk of mortality. Also, the other factors associated with COVID-19 mortality were longer LOS, older age, and kidney disease. Serum sodium values, longer LOS, older age, and kidney disease could be used for risk stratification in patients with COVID-19. Physicians treating COVID-19 should be made aware that patients with dysnatremia are at a higher risk for death than those presenting with eunatremic. Intervention studies would be needed to ascertain whether correction of dysnatremia could improve clinical evolution.