Relationship between Radiological Lung Findings and Laboratory Ferritin and D-Dimer Levels in Patients with COVID-19 Infection

Introduction: Pulmonary symptoms of COVID-19 infection range from asymptomatic infection to severe pneumonia. Pathogenesis and severity of symptoms were found to be related to the body’s immune response. Objec-tives: Ferritin and D-Dimer in COVID-19 confirmed cases can predict lung injury and possible poor patient prognosis. Materials and Methods: Patients who had been admitted to Dr. Sulaiman Alhabib-Arryan Hospital with positive COVID-19 polymerase chain reaction (PCR) tests between March 2020 and December 2021 were studied for blood ferritin and D-Dimer levels in relation to pulmonary radiological findings. Results: A total of 494 cases are included in this study. Male patients represent 74.1% of the cases, and the mean age is 51.68 ± 13.37 years. Increased age, ferritin, D-Dimer levels, and respiratory symptoms are factors that showed a statistically significant association with positive computed tomography (CT) findings. Receiver operator characteristic curve (ROC) showed that ferritin has a higher capability than D-Dimer to detect CT findings and that both are equal in predicting possible patient mortality. Suggested cutoff values for Ferritin


Background
Outbreaks of COVID-19 infection started to affect the world since last 2019 when it erupted in Wuhan, China and then the whole world. The WHO considered it a worldwide pandemic in March 2020 [1] [2].
Symptoms of COVID-19 infection range from asymptomatic infection to severe pneumonia, sepsis, acute respiratory distress syndrome and mortality due to respiratory failure and multi-organ dysfunction [2] [3].
The pathogenesis and severity of symptoms were found to be related to the body's immune response that will affect many body systems, including the hematological, epithelial, and vascular system [4].
Lung and vascular injuries occur secondary to the release of large amounts of inflammatory cytokines [4]. Virus replicating in respiratory epithelial cells will result in release of large amounts of these cytokines, causing severe lung disease [5].
The condition of the high inflammatory cytokines in the circulation of COVID-19 patients is known as cytokine storm. This storm is strongly associated with symptoms severity. Interleukins 2, 6, 7 and 10, TNF α and interferon γ [1] [3] [4] [5], are examples of some of those mediators. This rise in the inflammatory cytokines and associated apoptosis are the main causes of lymphopenia observed in COVID-19 patients, which was a feature in the severely ill and many hospitalized patients [6] [7] [8].
This massive release of inflammatory cytokines in COVID-19 patients is also associated with activation of the coagulation pathway and elevation of serum ferritin, making COVID-19 one of the causes of hyperferritinemic syndrome [9].
Activation of the coagulation pathway will cause arterial and venous thrombosis that will be aggravated by the presence of co-morbidities such as hypertension, lung disease, and diabetes [10].
Imaging studies gained by using computed tomography (CT) scan are considered a sensitive method for early detection of lung injury in pneumonia. Most CT findings are in the form of ground glass opacity (GGO), with or without consolidation, interlobular septal thickening, lymphadenopathy, and pleural effusion [10].

Aim of the Work
The present study was designed to clarify the diagnostic accuracy of using laboratory markers such as ferritin and D-Dimer in COVID-19 confirmed cases to

Study Population
The study was performed on patients who had been admitted to Dr. Sulaiman Alhabib-Arryan with a positive COVID-19 PCR test. clusion criteria were patients aged more than 75 and less than 18, pregnant females, any patient with iron deficiency anemia and any hyperferritinemic states such as sepsis due to bacterial, fungal or viral sources other than COVID-19, iron overload due to hemochromatosis or chronic transfusions, and chronic hemolytic anemia. Radiological and laboratory findings are collected from available data in the hospital information system (VIDA).

Study Variables
Patients were positive for COVID-19 by RT-PCR.
Pulmonary CT findings.

Statistical Analysis
Descriptive statistics are presented in the form of mean with standard deviation or median with Q1 and Q3 for numeric variables, while frequencies and percentages are used for categorical variables. Multiple logistic regression for the factors associated with positive CT findings while controlling for other variables.
Receiver operating characteristic (ROC) curve with area under the curve (AUC) were used to study the diagnostic ability and get the suitable cutoff points with corresponding sensitivity and specificity. The IBM SPSS Version 28 software for Windows was used for the statistical analysis, and MedCalc Version 20 was used for developing the ROC curves.  predict positive CT findings and to get the corresponding cutoff points with sensitivity and specificity. Ferritin showed better diagnostic capability as compared to D-Dimer as it has higher AUC (0.891) as compared to that of the D-Dimer (0.783), p-value < 0.001 (Table 3).

Results
ROC curve is used to study if ferritin or D-Dimer can be used to predict mortality and to get the corresponding cutoff points with sensitivity and specificity ( Figure 2). Ferritin showed no difference in diagnostic capability as compared to D-Dimer as its AUC (0.781) was not different from that of the D-Dimer (0.799), p-value = 0.584 (Table 4).

Discussion
Our study presents information on COVID-19 positive patients admitted to our For possible poor prognosis and mortality, the suggested cutoff point for  Respiratory Distress Syndrome (ARDS). They discovered that there was a significant increase in initial ferritin level at time of hospital admission with an AUC value of 0.86 CI (0.8% -1%) and a significant p-value (0.001), while D-Dimer level was not initially significant as an indicator of lung injury, but after few days of admission started to be of significant value (p-value < 0.001) [14].

Limitations
Being a retrospective study, during the data collection phase, many patients who were eligible for our criteria were excluded due to missing information such as ferritin or D-Dimer results. In addition, time from illness onset to hospital presentation may affect ferritin and D-Dimers values.

Conclusion
In this study, we found that laboratory markers such as ferritin and D-Dimer can be an accurate predictor of lung injury in COVID-19 patients and their increased values above our suggested cutoff (>336 ng/mL for ferritin, and >0.55 mg/L FEU for D-Dimer), are correlated with the presence of radiological CT findings not only that but also levels above 864.6 for ferritin and >1.46 mg/L FEU for D-Dimer can predict the poor patient prognosis and possible mortality if patient did not receive enough hospital care and close monitoring in hospital.
We thus argue that D-Dimer and ferritin levels measured at the time of admission to the emergency department can be taken into consideration to predict disease severity.