Serum ferritin as a predictive biomarker in COVID-19. A systematic review, meta-analysis and meta-regression analysis

Highlights

• Higher ferritin levels were found among COVID-19 patients (compared to control).

• Among COVID-19 patients, higher ferritin level was observed among patients with more severe disease or unfavorable outcome.

• However, many confounders can potentially influence the level of serum ferritin e.g. age, sex and concomitant co-morbidity.

Abstract

Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis evaluates serum ferritin level in different severity levels in COVID-19. Studies evaluating serum ferritin level in different clinical contexts (COVID-19 vs. control, mild to moderate vs. severe to critical, non-survivor vs. survivor, organ involvement, ICU and mechanical ventilation requirement) were included (total 9 literature databases searched). Metaanalysis and metaregression was carried out using metaphor “R” package. Compared to control (COVID-19 negative), higher ferritin levels were found among the COVID-19 patients [SMD −0.889 (95% C.I. −1.201, −0.577), I² = 85%]. Severe to critical COVID-19 patients showed higher ferritin levels compared to mild to moderate COVID-19 patients [SMD 0.882 (0.738, 1.026), I² = 85%]. In meta-regression, high heterogeneity was observed could be attributed to difference in “mean age”, and “percentage of population with concomitant co-morbidities”. Non-survivors had higher serum ferritin level compared to survivors [SMD 0.992 (0.672, 1.172), I² = 92.33%]. In meta-regression, high heterogeneity observed could be attributed to difference in “mean age” and “percentage of male sex”. Patients requiring ICU [SMD 0.674 (0.515 to 0.833), I² = 80%] and mechanical ventilation [SMD 0.430 (0.258, 0.602), I² = 32%] had higher serum ferritin levels compared to those who didn't. To conclude, serum ferritin level may serve as an important biomarker which can aid in COVID-19 management. However, presence of other co-morbid conditions/confounders warrants cautious interpretation.