Longitudinal Study of Prevalence of Sodium Abnormalities in Hospitalized Patients With COVID-19
Authors: Tzoulis Ploutarchos , Waung Julian , Bagkeris Emmanouil , Hussein Ziad , Biddanda Aiyappa , Cousins John , Dewsnip Alice , Falayi Kanoyin , McCaughran P W , Mullins Chloe , Naeem Ammara , Nwokolo Munachiso , Quah Helen , Bitat Syed Rabha , Deyab Eithar , Ponnampalam Swarupini , Bouloux Pierre-Marc Gilles , Montgomery Hugh , Baldeweg Stephanie 
Published: May 2021

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] &lt; 135 and &gt; 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 &lt; 130 mmol/L in 30 (6.2%). Only 19% of patients with &lt; 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.