Longitudinal Study of Prevalence of Sodium Abnormalities in Hospitalized Patients With COVID-19

Abstract

Background: Sodium abnormalities (dysnatremia) are frequently observed in patients with community-acquired pneumonia and are associated with excess mortality. Data on the prevalence of hyponatremia and hypernatremia (serum sodium [Na] < 135 and > 145 mmol/L respectively) in patients with coronavirus disease 19 (COVID-19) are currently lacking. Methods: The aim of this study was to evaluate the prevalence and etiology of hyponatremia and hypernatremia at several timepoints during hospitalization of COVID-19 patients. This retrospective, longitudinal, observational study included all COVID-19 positive adult patients admitted to two London hospitals over an 8-week period (February to May 2020). Results: Clinic records were reviewed in 488 patients, 277 males (56.8%) and 211 females (43.2%), with a median age of 68 years. Comorbidities were documented in 79.6%, with the commonest being hypertension (45.7%), diabetes mellitus (25%), and chronic kidney disease (16.4%). Prior to admission, 25 patients (5.1%) had pre-existing chronic hyponatremia. At hospital presentation, median [Na] concentration was 137 mmol/L. Dysnatremia was present in 146 patients (29.9%), including 26 (5.3%) with hypernatremia and 120 (24.6%) with hyponatremia, of whom [Na] was 130-134 mmol/L in 90 (18.4%) and < 130 mmol/L in 30 (6.2%). Only 19% of patients with < 130 mmol/L underwent adequate laboratory assessment of the etiology of hyponatremia. Of those, based on a urinary sodium cut-off of 30 mmol/L, hyponatremia was classified as hypovolemia in 75% and non-hypovolemic in 25%. For the remaining hyponatremic cases, using 5 mmol/L as the cut-off value for plasma urea, 55.7% were classified as probable hypovolemic and 44.3% non-hypovolemic hyponatremia. There was an upward trajectory of [Na] values during hospital stay with a median increase of 2 mmol/L in the first 48 hours following admission. On the fifth day of hospitalization, the prevalence was similar for hypernatremia and hyponatremia (13.8% and 14.1%, respectively). On the tenth day, hypernatremia was more common than hyponatremia (14.2% vs 10.2% respectively). Analysis of [Na] throughout the hospital stay defined four subgroups; 185 patients (37.9%) remained normonatremic throughout hospitalization; 180 (36.9%) had exposure to hyponatremia; 53 (10.9%) were exposed to hypernatremia; and 70 (14.3%) experienced both hypernatremia and hyponatremia. Conclusions: Hyponatremia, usually mild, was common at admission in Covid-19 positive patients, while hypovolemic hyponatremia appeared to be the predominant etiology. During hospital stay, abnormal sodium concentration was recorded in more than two thirds of Covid-19 positive patients. The association of dysnatremia with the outcomes in hospitalized COVID-19 patients warrants further exploration.

Epidemiology and outcomes of hyponatremia in patients with COVID-19—A territory-wide study in Hong Kong

“…An association between COVID-19 and hyponatremia is well-recognized, with studies reporting incidences of hyponatremia of up to 25% (13)(14)(15)(16)(17)(18)(19)(20). Hyponatremia was associated with severity of pulmonary infiltrates, need for intubation and mechanical ventilation, and death.…”

Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients

“…Hyponatremia in COVID-19 is observed in 20.5% to 35.8% of cases at admission (6,7). Furthermore, hyponatremia has been detected at some point during hospitalization in 36.9% of COVID-19 patients (8). Although hyponatremia in COVID-19 is habitually mild, hyponatremic patients have been found to be at an increased risk for in-hospital mortality and sepsis (7,(9)(10)(11) as well as for sepsis-related death (12).…”

“…SNa values at the 2nd-3rd day of hospitalization were available in 180 of the patients in whom volemic data were registered. SNa was measured during hospitalization a median of 6 days [3.5-10] in hypovolemic and 5 days [4][5][6][7][8][9][10] in euvolemic patients, with SNa values determined in 58% and 50% (p= 0.230) of the days of hospital stay of these patients respectively. The median nadir SNa during hospitalization was 132 mmol/L [129-133] in hypovolemic and 133 mmol/L [131-134] in euvolemic subjects (p= 0.158).…”

Endothelial dysfunction in autoimmune, pulmonary, and kidney systems, and exercise tolerance following SARS-CoV-2 infection

“…These include hypothalamic-pituitaryadrenal (HPA) axis dysfunction with critical illness-related corticosteroid insufficiency; direct cytopathic impact of the virus on the adrenals, pituitary, and hypothalamus; immune-mediated inflammation; small vessel vasculitis; microthrombotic events; resistance of cortisol receptors; and impaired post-receptor signaling; and dissociation of adrenocorticotropic hormone and cortisol regulation (37). Hyponatremia is a common finding in acute COVID-19 infection and serum sodium levels <135 mmol/L may be associated with poorer outcomes (38). It could result from syndrome of inappropriate antidiuretic hormone secretion, hypovolemia as well as adrenal insufficiency.…”