Ferritin and Hemoglobin as Predictors of Fatal Outcome in COVID-19: Two Sides of the Same Coin

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have multisystemic involvement with hyperinflammation being a cardinal feature and deranged iron metabolism having a possible role. In this premise, we studied the prognostic value of two markers of iron metabolism ferritin and hemoglobin.

A retrospective-cohort study was carried out in a tertiary hospital in northern India involving 210 hospitalized COVID-19 patients aged 15-and above. Analysis was done for clinical profile, comorbidities and basic laboratory indices including ferritin-hemoglobin ratio (FHR) with primary end-point being in-hospital all-cause mortality.

Median serum ferritin levels (640.00ng/mL vs 220.00ng/mL) were significantly higher among non-survivors as against survivors while median hemoglobin levels were significantly lower (12.12g/dL vs 13.73g/dL). Serum ferritin levels >400ng/mL (Sn 80%, Sp 70%) predicted mortality with high sensitivity and specificity. Notably, serum ferritin levels >400ng/mL (HR 11.075 [1.481-82.801]) and anemia, defined as a hemoglobin of <12g/dL for females and < 13g/dL for males and were significantly associated with the risk of mortality in a univariable Cox-proportional hazards regression. The median FHR was significantly higher among non-survivors compared to survivors (56.98 vs 17.17). FHR>31 (Sn 85% Sp 71.6%) was highly sensitive and specific for predicting mortality. The multivariable analysis indicated that FHR >31 remained an independent risk factor for mortality (HR 12.293 [3.147-48.028]).

Ferritin-hemoglobin ratio (FHR), which encompasses into a single index, the effects of both elevated levels of ferritin and the severity of anemia, seems to perform particularly well as a prognostic marker and emerged as an independent risk factor for mortality in COVID-19 patients. Hyperferritinemia and anemia, both, are inexorably interlinked in addition to having a role, directly or indirectly in the disease pathophysiology. Ferritin and hemoglobin, hence should be seen as two sides of the same coin rather than as two discrete entities.