Associations and prognostic accuracy of electrolyte imbalances in predicting poor COVID-19 outcome: a systematic review and meta-analysis

ABSTRACT Background Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. Objectives To systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. Methods PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR+, LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. Results We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR=2.08, 95%CI=1.48-2.94, I 2 =93%, N=8), hypernatremia (OR=4.32, 95%CI=3.17-5.88, I 2 =45%, N=7) and hypocalcemia (OR=3.31, 95%CI=2.24-4.88, I 2 =25%, N=6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR+ 4.0, PPV=55%, AUC=0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV=87%, AUC=0.71). Overall quality of evidence ranged from very low to moderate. Conclusion Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.