Dysnatraemia During COVID-19 Diagnosis and Background Hyponatraemia are Associated with Adverse Clinical Outcomes of COVID-19

Abstract

Background: Data on the impact of dysnatraemia and pre-existing hyponatraemia on clinical outcomes of COVID-19 remains elusive.

Methods: We performed a territory-wide retrospective cohort study of COVID-19 patients between 23 January 2020 and 1 January 2021 in Hong Kong. The primary endpoint was all-cause mortality. The secondary endpoint was intensive care unit (ICU) admission and/or use of invasive mechanical ventilation (IMV). Mild hyponatraemia, moderate-to-severe hyponatraemia, normonatraemia, and hypernatraemia were defined as serum sodium of 130-<135, <130, 135-145, and >145 mmol/L , respectively. Background sodium level was measured at least one month before COVID-19 diagnosis.

Findings: Of 8,407 patients, 738 (8·8%), 143 (1·7%), and 24 (0·3%) had mild hyponatraemia, moderate-to-severe hyponatraemia, and hypernatraemia at COVID-19 diagnosis, respectively. At a median follow-up of 12 days, 156 (1·9%) patients died; 413 (4·9%) patients were admitted to ICU and/or required IMV use. M oderate-to-severe hyponatraemia (adjusted hazard ratio [aHR] 2·92, 95% CI 1·59–5·36, P <0·001) and hypernatraemia (aHR 7·60, 95% CI 5·16–11·20, P <0·001) were independently associated with an increased mortality rate. Mild (adjusted cause-specific HR [aCSHR] 1·94) and moderate-to-severe hyponatraemia (aCSHR 2·08) were independently associated with a higher rate of ICU admission/IMV use. Hypernatraemia was not associated with a higher rate of ICU admission/IMV use, yet was associated with a higher rate of competing death. Background hyponatraemia was associated with a higher rate of mortality.

Interpretation: COVID-19 patients with dysnatraemia are associated with adverse clinical outcomes, in whom vigilant monitoring of serum sodium would be important.

Funding Information: This work was supported by the Health and Medical Research Fund (HMRF) – Food and Health Bureau Commissioned Research on COVID-19 (Reference: COVID1903002).

Declaration of Interests: Terry Yip has served as an advisory committee member and a speaker for Gilead Sciences. Jeremy Teoh has served as an advisory committee member and a speaker for Astellas, Ferring and Janssen, and he has received research grants from Janssen and Ferring. Grace Lui has served as an advisory committee member for Gilead, Merck and GSK, speaker for Merck and Gilead, and received research grant from Gilead, Merck, Janssen and GSK. Vincent Wong has served as an advisory committee member for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Janssen, Novartis, Novo Nordisk, Perspectum Diagnostics, Pfizer, TARGET-NASH and Terns; and a speaker for Bristol-Myers Squibb, Echosens, Gilead Sciences and Merck. He has also received a research grant from Gilead Sciences. Henry Chan is an advisor for AbbVie, Aptorum, Arbutus, Hepion, Intellia, Janssen, Gilead, GSK, GRAIL, Medimmune, Merck, Roche, Vaccitech, VenatoRx, Vir Biotechnology, Virion Therapeutics; and a speaker for Mylan, Gilead and Roche. David Hui has served as an advisory committee member for Roche. Cheuk-Chun Szeto has served as an advisory committee member for Baxter Healthcare and Novartis. Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Furui, Gilead Sciences, Janssen and Roche, and received research grant from Gilead Sciences. The other authors declare that they have no competing interests.

Ethics Approval Statement: The study protocol was approved by the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee (Reference number: 2020·074).

Keywords: intensive care unit, invasive mechanical ventilation, mortality, SARS-CoV-2, sodium abnormality