Utility of Ferritin, Procalcitonin, and C-reactive Protein in Severe Patients with 2019 Novel Coronavirus Disease

It is of clinical significance to evaluate the disease severity and investigate possible biomarkers of 2019 Novel coronavirus disease (COVID-19). In this study, we aim to describe the clinical characteristics of infection makers in severe and very severe patients with COVID-19. This is a single center, observational analysis. We enrolled 48 in-hospital severe patients with COVID-19 admitted to the West District of Union Hospital of Tongji Medical College and analyzed infection biomarkers in 20 patients who had been tested for ferritin, PCT, CRP, etc.

Although most patients have mild symptoms and good prognosis, severe COVID-19 cases may present with acute respiratory distress syndrome (ARDS) and systemic inflammation.
Thus, it is urgent to evaluate the disease severity and investigate possible biomarkers so as to make fast and correct clinical decisions. One recent study has pointed out that the patients with COVID-19 usually have increased serum C-reactive protein (CRP) (58.3%), lactate dehydrogenase (LDH) (57.0%) and erythrocyte sedimentation rate (ESR) (41.8%) 14 .
But more evidence regarding other infection markers in COVID-19 needs further study. Of note, previous studies have established ferritin as a possible inflammation marker in pneumonia, associating with the progression of bacterial and viral infection. However, no evidence has been released how ferritin is altered in COVID-19.
In the present single center, observational analysis, we explored the infection biomarkers, including ferritin, procalcitonin (PCT), and CRP in in-hospital patients with severe and very severe COVID-19. We aim to describe the clinical characteristics of infection makers in severe and very severe patients with COVID-19. Results 9 patients with severe and 11 with very severe COVID-19 were included in this analysis.

Study design and participants
Baseline data for the cases enrolled were shown in Table 1    Fisher's exact test was then applied to compare the rate with abnormal LDH, CRP, PCT, ferritin and blood count between severe and very severe COVID-19, and relative risk was calculated. The results showed that PCT and PLT count had statistical significance (P < 0.05), and CRP, ferritin and LY% had towards statistical significance (P = 0.07) ( Table 3), indicating that PCT, CRP, ferritin, LY% and PLT count might be possible markers for the progression of disease in severe and very severe COVID-19. In the present analysis, we firstly evaluated serum ferritin levels in COVID-19, which are significantly elevated during critical infection. The function of ferritin including iron binding and storage is associated with the immune and inflammatory response 16 . The reasons of increased ferritin include bacterial and/or viral infection, hemochromatosis and long-term transfusion 17 . When bacterial and/or viral infection takes place, the increase of serum ferritin is related to the release of iron in the reticuloendothelial system, the decrease of the ability of transporting ferritin in liver and spleen, and increased synthesis and release of intracellular ferritin 18,19 . Some studies showed that patients with bacterial infection had higher ferritin level compared to viral infection 20,21 . Previous review has also proposed a model that the inflammatory response to viral (IL-18/ferritin) presents as specific plasma patterns of immune biomarkers 17 . Moreover, elevation of serum ferritin levels predicts a poor outcome in hospitalized patients with influenza infection 16 . In the present study, the patients in severe and very severe COVID-19 both exhibits increase serum ferritin level, but the serum ferritin in very severe COVID-19 group is significantly higher than that of severe COVID-19 group. The increased ferritin might indicate severe secondary bacterial infection in COVID-19, and might be utilized as a marker of poor prognosis.
As we known, when inflammation or tissue damage happens, CRP can be significantly increased in serum, which is usually used as a unique inflammatory marker in the current clinical practice 22 . On the other hand, PCT, as the precursor of calcitonin, is a kind of glycoprotein without hormone activity, which is significantly higher in bacterial infection, but remain normal or slightly increased in viral infection 22,23

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

This study was funded by the Clinical Research Award of the First Affiliated Hospital of
Xi'an Jiaotong University, China (No.XJTU1AF-CRF-2018-025).

Competing interests
The authors declare that they have no competing interests.

Authors' contributions
BZ, XM and YW collected the clinical and laboratory data. JS processed statistical analysis.
JS and BZ drafted the manuscript. BZ, XM and YW revised the final manuscript. BZ, XM and YW is responsible for all clinical and laboratory data.