Hypoferremia predicts hospitalization and oxygen demand in COVID-19 patients

Hippchen, T.; Altamura, S.; Muckenthaler, M. U.; Merle, U.

Background: Iron metabolism might play a crucial role in cytokine release syndrome in COVID-19 patients. Therefore we assessed iron metabolism markers in COVID-19 patients for their ability to predict disease severity. Methods: COVID-19 patients referred to the Heidelberg University Hospital were retrospectively analyzed. Patients were divided into outpatients (cohort A, n=204), inpatients (cohort B, n=81), and outpatients later admitted to hospital because of health deterioration (cohort C, n=23). Results: Iron metabolism parameters were severely altered in patients of cohort B and C compared to cohort A. In multivariate regression analysis including age, gender, CRP and iron-related parameters only serum iron and ferritin were significantly associated with hospitalization. ROC analysis revealed an AUC for serum iron of 0.894 and an iron concentration <6micromol/l as the best cutoff-point predicting hospitalization with a sensitivity of 94.7% and a specificity of 67.9%. When stratifying inpatients in a low- and high oxygen demand group serum iron levels differed significantly between these two groups and showed a high negative correlation with the inflammatory parameters IL-6, procalcitonin, and CRP. Unexpectedly, serum iron levels poorly correlate with hepcidin. Conclusion: We conclude that measurement of serum iron can help predicting the severity of COVID-19. The differences in serum iron availability observed between the low and high oxygen demand group suggest that disturbed iron metabolism likely plays a causal role in the pathophysiology leading to lung injury.