European Journal of Cardiovascular Medicine

Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has emerged as a global pandemic since its identification in Wuhan, China, in December 2019. The clinical presentation of COVID-19 ranges from asymptomatic infection to severe pneumonia, acute respiratory distress syndrome (ARDS), multiorgan failure, and death [1]. Early identification of patients at risk of progression to severe disease is critical in the effective triage and management of COVID-19 patients [2].

Inflammatory markers such as C-Reactive Protein (CRP), D-dimer, and Ferritin are significantly altered in COVID-19, correlating with disease severity and prognosis [3]. CRP is an acute-phase reactant synthesized by the liver in response to interleukin-6 (IL-6) and is considered a reliable marker of inflammation and tissue damage [4]. Elevated CRP levels have been associated with severe COVID-19 and may reflect the intensity of the cytokine storm [5]. D-dimer, a fibrin degradation product, is an established marker of coagulation activation and fibrinolysis. Several studies have reported elevated D-dimer levels in COVID-19 patients, especially those with severe disease or poor outcomes. This has been linked to the prothrombotic state associated with SARS-CoV-2 infection and the increased risk of venous thromboembolism [6,7]. Ferritin, an iron-storage protein, also acts as an acute-phase reactant. Elevated ferritin levels in COVID-19 have been considered a surrogate marker for the hyperinflammatory state and may serve as a predictor of disease severity [8,9]. Hyperferritinemia in COVID-19 is believed to be a consequence of macrophage activation and cytokine storm, especially in critically ill patients [10].

Given the prognostic value of these biomarkers, their evaluation can assist clinicians in predicting disease progression, guiding therapeutic decisions, and improving patient outcomes. This study aims to assess and compare the levels of CRP, D-dimer, and ferritin among COVID-19-positive patients admitted to wards versus those requiring intensive care. The study also explores the correlation of these biomarkers with age and gender.

This Retrospective Observational Study was conducted in the Department of Pathology, Central Laboratory, Rajiv Gandhi Super Speciality Hospital (RGSSH), OPEC Campus, Raichur Institute of Medical Sciences (RIMS), Raichur – a tertiary care teaching hospital in Karnataka, India.

Study Duration

The study was conducted over 12 months, from June 2021 to May 2022.

Study Population

The study included 400 patients who tested positive for COVID-19 (RT-PCR confirmed) and were admitted either to the ward or the intensive care unit (ICU) of the hospital during the study period.

Inclusion Criteria

• Patients aged above 1 year.
• Laboratory-confirmed COVID-19 positive cases , by RT-PCR.
• Patients are admitted to either the ICU or the In-Patient ward.
• Patients with available laboratory data for CRP, D-dimer, and ferritin levels.

Exclusion Criteria

• Patients with incomplete medical or laboratory records.
• Patients with known chronic inflammatory conditions or malignancies that may affect CRP, D-dimer or Ferritin levels.
• Re-admissions of the same patient were excluded (only the first admission considered).

Data Collection

Data was collected retrospectively from hospital medical records and laboratory information systems (LIS). The following variables were documented:

• Demographic data: Age, gender.
• Clinical data: Place of admission (ICU or ward), outcome.
• Laboratory parameters: Serum C-Reactive Protein (CRP), D-dimer, and Serum Ferritin levels measured at the time of admission.

Laboratory Methods

• CRP levels were measured using a high-sensitivity Turbidimetric Immunoassay method.
• D-dimer levels were estimated using an Immunoturbidimetric method calibrated in ng/mL.
• Serum ferritin was measured using a Enzyme linked Fluorescent Assay(ELFA) Method

All laboratory investigations were conducted following standard operating procedures (SOPs) using automated analyzers available in the central laboratory of RGSSH,(OPEC), RIMS ,Raichur.

Ethical Considerations

As this was a Retrospective Study based on existing records, formal informed consent was waived. However, the study was conducted following the principles of the Declaration of Helsinki, and patient confidentiality was strictly maintained. Institutional ethical clearance was obtained before data retrieval and analysis.

Statistical Analysis

• Data were entered and analyzed using SPSS software version 25.0.
• Descriptive statistics such as frequencies, percentages, means, and standard deviations were used.
• Comparison between groups (ICU vs. ward, male vs. female, different age groups) was done using independent t-tests or ANOVA, wherever applicable.
• A P-value < 0.05 was considered statistically significant.

Table 1: Distribution of study participants based on Gender.

 Among the 400 persons studied, 167 (41.7%) were females and 233 (58.3%) were males.

Table 2: Distribution of study participants based on Age group.

 Among the 400 persons studied, 28 (7%) belonged to the age group of 1- 20 years, 126 (31.5%) were aged 21-40 years, and 162 (40.5%) were aged 41- 60 years, 74 (18.5%) were aged between 61 -80 years, and only 10 (2.5%) were aged above 80 years .

Table 3: Distribution of study participants based on place of admission/outcome.

 Among the studied population, 225 (56.2%) were admitted to the ward and 175 (43.8%) were admitted to the ICU.

Table 4: Comparison of Blood parameters with the admission outcome.

 There was a statistically significantly higher CRP & D-dimer level in those admitted to the ICU compared to those admitted to the ward. Even though there was a higher Ferritin level in those admitted to the ICU compared to those admitted to the ward but the difference was not statistically significant.

Table 5: Comparison of Blood Parameters by gender.

             There was no statistically significant difference in levels of CRP, D-dimer & Ferritin levels with the gender. 

Table 6: Comparison of admission outcomes by gender.

                                    There was no statistically significant difference in admission outcome by gender.

Table 7: Comparison of admission outcomes by Age group.

 There was a statistically significant difference in admission outcome with respect to age. The highest ICU admission rate (70%) was seen in the age group >80 years, followed by 55.4% ICU admission in the 61-80 years. The lowest ICU admission rate was seen in those belonging to the age group of 21 -40 years.

Table 8: Comparison of Blood Parameters with the Age group.

 There was a statistically significant difference with respect to D-Dimer level and age group. Higher D -Dimer level was seen in those aged above 80 years. There was no statistically significant difference in CRP and Ferritin levels with respect to age group.

The present study evaluates the levels of inflammatory biomarkers -CRP, D-dimer, and Ferritin—in COVID-19 positive patients, comparing those admitted to general wards versus those requiring intensive care. The findings are consistent with a growing body of evidence indicating that elevated levels of these biomarkers are associated with increased disease severity and poor outcomes in COVID-19.

Our study demonstrated significantly higher CRP levels in ICU patients compared to those in the general wards, suggesting its role as a sensitive marker of inflammation and disease severity. This is supported by Tan et al. who reported that elevated CRP levels correlated well with CT findings and disease progression in early-stage COVID-19 [4]. Similarly, Liu et al. emphasized the prognostic value of CRP in predicting severity and poor clinical outcomes [5]. D-dimer levels were also markedly increased in ICU patients, underscoring the prothrombotic complications frequently observed in severe COVID-19. Elevated D-dimer has been consistently linked to higher risk of venous thromboembolism, disseminated intravascular coagulation (DIC), and mortality [6,7]. Zhang et al. reported that D-dimer levels on admission were significantly higher in non-survivors and were a strong independent predictor of in-hospital mortality [6]. Tang et al. also demonstrated that abnormal coagulation parameters, particularly elevated D-dimer, were closely associated with adverse outcomes [7]. Ferritin, a key acute-phase reactant, was also significantly elevated in critically ill patients in our cohort. This finding aligns with earlier studies by Vargas-Vargas and Cheng et al., who found that ferritin levels were significantly higher in patients with severe or critical illness and may be reflective of the hyperinflammatory response or "cytokine storm" observed in advanced stages of COVID-19 [8,9]. High ferritin levels are hypothesized to result from excessive macrophage activation and systemic inflammation, which can cause multiorgan damage [10]. Additionally, our study found that male patients and older individuals tended to have higher levels of these biomarkers, corroborating previous reports that advanced age and male gender are associated with worse outcomes in COVID-19. This may be due to differences in immune response, prevalence of comorbidities, or hormonal influences that modulate inflammatory activity [2,3].

Overall, the data suggest that these inflammatory markers—CRP, D-dimer, and Ferritin—can serve not only as a diagnostic tool but also as useful prognostic indicators for clinicians to stratify patients according to risk, guide therapeutic decisions, and allocate healthcare resources more effectively. Early identification of patients with elevated biomarkers could help initiate timely interventions, potentially reducing morbidity and mortality.

The present study highlights the significant association between elevated levels of inflammatory biomarkers—C-reactive protein (CRP), D-dimer, and Ferritin—and the severity of COVID-19 infection. Patients admitted to the ICU exhibited markedly higher levels of these markers compared to those in , In-Patient wards, indicating that these parameters can serve as important indicators of disease progression and severity.

Among the three biomarkers, D-dimer and Ferritin showed particularly strong correlations with critical illness, suggesting their utility not only in early identification of patients at risk for complications , but also in guiding clinical management and resource allocation. Additionally, the study underscores the influence of age and gender, with older patients and males more likely to exhibit elevated biomarker levels and poorer outcomes.

In conclusion, routine monitoring of CRP, D-dimer, and Ferritin levels in COVID-19 patients may facilitate early risk stratification and timely therapeutic interventions, potentially improving prognosis and reducing mortality. Further large-scale, multi-center studies are recommended to validate these findings and to develop standardized biomarker thresholds for clinical decision-making in COVID-19 management.

1.       Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.

2.       Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062.

3.       Zeng F, Huang Y, Guo Y, et al. Association of inflammatory markers with the severity of COVID-19: a meta-analysis. Int J Infect Dis. 2020;96:467–474.

4.       Tan C, Huang Y, Shi F, et al. C-reactive protein correlates with CT findings and predicts severe COVID-19 early. J Med Virol. 2020;92(7):856–862.

5.       Liu F, Li L, Xu M, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370.

6.       Zhang L, Yan X, Fan Q, et al. D‐dimer levels on admission to predict in‐hospital mortality in patients with COVID-19. J Thromb Haemost. 2020;18(6):1324–1329.

7.       Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–847.

8.       Vargas-Vargas M, Cortés-Rojo C. Ferritin levels and COVID-19. Rev Panam Salud Publica. 2020;44:e72.

9.       Cheng L, Li H, Li L, et al. Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. J Clin Lab Anal. 2020;34(10):e23618.

10.    Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–1034.