AUTHOR=Ayus Juan Carlos , Negri Armando Luis , Moritz Michael L. , Lee Kyung Min , Caputo Daniel , Borda Maria Elena , Go Alan S. , Eghi Carlos 

TITLE=Hyponatremia, Inflammation at Admission, and Mortality in Hospitalized COVID-19 Patients: A Prospective Cohort Study

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.748364

DOI=10.3389/fmed.2021.748364

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Systemic inflammation has been associated with severe coronavirus disease 2019 (COVID-19) disease and mortality. Hyponatremia can result from inflammation due to non-osmotic stimuli for vasopressin production.</p><p><bold>Methods:</bold> We prospectively studied 799 patients hospitalized with COVID-19 between March 7 and November 7, 2020, at Hospital Posadas in Buenos Aires, Argentina in order to evaluate the association between hyponatremia, inflammation, and its impact on clinical outcomes. Admission biochemistries, high-sensitivity C-reactive protein (hsCRP), ferritin, patient demographics, and outcome data were recorded. Outcomes (within 30 days after symptoms) evaluated included ICU admission, mechanical ventilation, dialysis-requiring acute kidney injury (AKI), and in-hospital mortality. Length of hospital stay (in days) were evaluated using comprehensive data from the EHR.</p><p><bold>Results:</bold> Hyponatremia (median Na = 133 mmol/L) was present on admission in 366 (45.8%). Hyponatremic patients had higher hsCRP (median 10.3 [IR 4.8–18.4] mg/dl vs. 6.6 [IR 1.6–14.0] mg/dl, <italic>p</italic> &lt; 0.01) and ferritin levels (median 649 [IQR 492–1,168] ng/dl vs. 393 [IQR 156–1,440] ng/dl, <italic>p</italic> = 0.02) than normonatremic patients. Hyponatremia was associated with higher odds of an abnormal hsCRP (unadjusted OR 5.03, 95%CI: 2.52–10.03), and remained significant after adjustment for potential confounders (adjusted OR 4.70 [95%CI: 2.33–9.49], <italic>p</italic> &lt; 0.01). Hyponatremic patients had increased mortality on unadjusted (HR 3.05, 95%CI: 2.14–4.34) and adjusted (HR 2.76, 95%CI:1.88–4.06) in Cox proportional hazard models. Crude 30-day survival was lower for patients with hyponatremia at admission (mean [SD] survival 22.1 [0.70] days) compared with patients who were normonatremic (mean [SD] survival 27.2 [0.40] days, <italic>p</italic> &lt; 0.01).</p><p><bold>Conclusion:</bold> Mild hyponatremia on admission is common, is associated with systemic inflammation and is an independent risk factor for hospital mortality.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="http://www.ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.ClinicalTrials.gov</ext-link>, identifier NCT04493268.</p>