Osmolality as a strong predictor of COVID-19 mortality and its possible links to other biomarkers

Osmolality, concentration of solute particles, was rarely used for prognosis for COVID-19. By analyzing blood samples of more than 1300 COVID-19 patients from Tokat, Turkey (including 100 surviving and 30 deceased inpatients), we found calculated osmolality to be an excellent prognostic biomarker for mortality and significantly associated with hospitalization, independent from gender and age. Although calculated osmolality is defined as a weighted sum of sodium, glucose, and urea, the three are not necessarily independent. Other blood test biomarkers, ferritin, creatine, and chloride are also correlated with osmolality after conditioning on age. By applying a combination of collider analysis and mediation analysis, we design a pipeline to construct a causal model among all these variables in their relationship to osmolality. We confirm that while glucose and sodium are independent contributors of osmolality, glucose and urea, urea and sodium are correlated. We also conclude that ferritin and creatine are associated with osmolality through urea, and chloride's association to osmolality is through sodium.