Hypoosmolar and hyperosmolar COVID-19 patients are predisposed to dismal clinical outcomes

Abstract

We aimed to investigate the associations of hypo- and hyperosmolarity at hospital admission with clinical characteristics and outcomes in 5645 consecutive hospitalized COVID-19 patients treated at a tertiary-level institution. Serum osmolarity was calculated as 2x Na (mmol/L) + urea (mmol/L) + glucose (mmol/L), with normal range from 275 to 295 mOsm/L. Median serum osmolarity was 292.9 mOsm/L with 51.8% normoosmolar, 5.3% hypoosmolar and 42.9% hyperosmolar patients present at the time of hospital admission. Hypoosmolarity was driven by hyponatremia, and was associated with the presence of chronic liver disease, liver cirrhosis, active malignancy and epilepsy. Hyperosmolarity was driven by an increase in urea and glucose and was associated with the presence of chronic metabolic and cardiovascular comorbidities. Both hypo- and hyperosmolar patients presented with more severe COVID-19 symptoms, higher inflammatory status, and experienced higher mortality in comparison to normoosmolar patients. In multivariate analysis, hypoosmolarity (adjusted odds ratio (aOR)=1.39, p = 0.024) and hyperosmolarity (aOR = 1.9, p < 0.001) remained significantly associated with higher mortality independently of older age, male sex, higher Charlson Comorbidity Index and more severe COVID-19. Disruptions in serum osmolarity are frequent in COVID-19 patients, may be easy to detect and target therapeutically, and thus potentially moderate associateds poor prognosis.

Keywords:

• Osmolarity
• osmolality
• mortality
• mechanical ventilation
• comorbidities

Acknowledgments

This paper is a part of the project ‘Registar hospitalno liječenih bolesnika u Respiracijskom centru KB Dubrava/Registry of hospitalized patients in University Hospital Dubrava Respiratory center’ registered on the ClinicalTrials.gov website, identifier NCT05151094. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The study was approved by the University Hospital Dubrava Review Board (Nm: 2022/0706-10). Due to retrospective nature of the study informed consent was not required and was waived by the Review Board.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data is available from the corresponding author on reasonable request.