European Journal of Cardiovascular Medicine

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. Since its initial identification in Wuhan, China, in late 2019, COVID-19 has rapidly spread worldwide, resulting in substantial morbidity and mortality and overwhelming healthcare systems across continents¹. The clinical spectrum of COVID-19 is broad, ranging from asymptomatic infection to severe pneumonia, acute respiratory distress syndrome (ARDS), multi-organ dysfunction, and death². Identifying reliable biomarkers that can predict disease severity and guide clinical management remains a critical need, especially in resource-constrained settings.

Among the numerous biomarkers investigated, serum ferritin has garnered considerable attention due to its dual role as an iron-storage protein and an acute-phase reactant. Ferritin is primarily involved in iron homeostasis, but its levels rise markedly in response to systemic inflammation and infection³. In the context of COVID-19, hyperferritinemia has been frequently observed, particularly among patients with severe disease and those experiencing cytokine storm syndromes⁴. Elevated ferritin levels are thought to reflect the underlying hyperinflammatory state, which is a hallmark of severe COVID-19 and is associated with adverse clinical outcomes⁵.

Several studies have highlighted the prognostic significance of serum ferritin in COVID-19. For example, Zhou et al. reported that non-survivors of COVID-19 had significantly higher ferritin levels compared to survivors, suggesting a strong association between hyperferritinemia and mortality⁶. Similarly, a meta-analysis by Cheng et al. demonstrated that elevated ferritin levels were consistently linked to increased disease severity and poor prognosis in COVID-19 patients⁷. These findings underscore the potential utility of ferritin as a biomarker for early risk stratification and monitoring of disease progression.

The pathophysiological mechanisms underlying ferritin elevation in COVID-19 are complex and multifactorial. Ferritin, as an acute-phase protein, is upregulated in response to pro-inflammatory cytokines such as interleukin-6 (IL-6), which are abundantly produced during the cytokine storm phase of severe COVID-19⁸. This hyperinflammatory response not only contributes to tissue damage and organ dysfunction but also amplifies the release of ferritin from damaged cells⁹. Moreover, ferritin itself may play a pathogenic role by promoting further immune activation and oxidative stress, thereby perpetuating the inflammatory cascade¹⁰.

Demographic factors and comorbidities also influence the relationship between ferritin levels and COVID-19 severity. Older age, male sex, and the presence of underlying conditions such as diabetes, hypertension, and cardiovascular disease have been associated with both higher ferritin levels and worse clinical outcomes¹¹. These associations highlight the importance of considering patient-specific factors when interpreting ferritin measurements and making clinical decisions.

Despite the growing body of evidence supporting the role of serum ferritin as a prognostic marker in COVID-19, there remain gaps in our understanding regarding its precise correlation with disease severity across different populations and clinical settings. Most existing studies have been conducted in large tertiary care centers or within specific geographic regions, and there is a need for additional research to validate these findings in diverse cohorts¹². Furthermore, the interplay between ferritin and other inflammatory markers, as well as its potential utility in guiding therapeutic interventions, warrants further exploration.

In this context, the present study aims to investigate the correlation between serum ferritin levels and disease severity in patients with COVID-19. By analyzing clinical and laboratory data from a cohort of COVID-19 patients, this study seeks to elucidate the prognostic value of ferritin and its association with demographic factors, comorbidities, and other inflammatory markers. The findings are expected to contribute to the growing evidence base and inform clinical practice regarding the use of ferritin in the management of COVID-19.

This was a hospital-based, observational, cross-sectional study conducted at a tertiary care center in Central India over a period of one year.A total of 80 adult patients (≥18 years) admitted with laboratory-confirmed COVID-19 infection by reverse transcriptase-polymerase chain reaction (RT-PCR) were enrolled after obtaining informed consent. Patients of both sexes were included. Exclusion criteria were applied to minimize confounding influences on ferritin levels and included individuals with known hematological disorders, chronic liver disease, recent blood transfusion (within the last 3 months), or those receiving iron supplements or immunosuppressive therapy.

Detailed demographic data including age, sex, and comorbidities (such as diabetes, hypertension, and chronic respiratory illness) were recorded. Clinical symptoms like fever, cough, breathlessness, fatigue, and gastrointestinal disturbances were noted at the time of admission. Blood samples were collected within 24 hours of hospitalization to assess serum ferritin levels and other inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), and D-Dimer. Serum ferritin was measured using a standardized chemiluminescent immunoassay method in the hospital’s central diagnostic laboratory.

Patients were classified into three groups based on disease severity: mild, moderate, and severe, according to the Ministry of Health and Family Welfare (MoHFW), Government of India, clinical criteria. Mild cases had no breathlessness or hypoxia, moderate cases exhibited pneumonia with oxygen saturation (SpO₂) between 90–94% on room air, and severe cases showed respiratory distress, SpO₂ <90%, or respiratory rate >30/min.

Data were analyzed using IBM SPSS Statistics version [Insert Version]. Descriptive statistics such as mean and standard deviation were used for continuous variables, and frequency and percentage were used for categorical variables. Comparison of ferritin levels among severity groups was performed using one-way ANOVA. Independent t-tests were used for comparison between sexes. Pearson correlation analysis was applied to determine the relationship between serum ferritin and other inflammatory markers. A p-value <0.05 was considered statistically significant.

Table 1: Demographic Characteristics of the Study Population (n = 80)

This table summarizes the demographic profile of the 80 COVID-19 patients, including age distribution and pre-existing comorbidities, split by sex (45 males and 35 females). It highlights that the majority of patients fall within the 40–59 age group, with a fair representation across all age brackets. Common comorbidities like diabetes and hypertension are noted in a significant portion of patients, which are important to consider as potential risk factors influencing disease severity and serum ferritin levels.

Table 2: Clinical Presentation of COVID-19 Patients

This table outlines the frequency of presenting symptoms among patients at the time of admission. Fever, cough, and shortness of breath were the most commonly reported symptoms, followed by fatigue and sore throat. A small percentage of patients were asymptomatic. This clinical snapshot helps identify the prevalent symptom patterns and may support correlation analysis between symptom severity and serum ferritin levels.

Table 3: Disease Severity Classification

In this table, patients are classified into mild, moderate, and severe categories based on clinical severity, with corresponding mean serum ferritin levels reported. The data clearly show a progressive rise in ferritin levels with increasing disease severity, supporting the hypothesis that serum ferritin may serve as a biomarker for disease progression in COVID-19 patients.

Table 4: Mean Serum Ferritin Levels by Sex and Severity

This table compares mean serum ferritin levels across different severity categories, further stratified by sex. It reveals that male patients tend to have higher ferritin levels than females within each severity group, suggesting a potential sex-based difference in inflammatory response. However, the trend of increasing ferritin with worsening severity is consistent across both sexes.

Table 5: Correlation Between Ferritin Levels and Inflammatory Markers

The final table correlates serum ferritin levels with other inflammatory markers—CRP, IL-6, and D-Dimer—across severity levels. All markers, including ferritin, show a consistent upward trend from mild to severe disease, indicating a strong association between systemic inflammation and disease severity. This reinforces the utility of ferritin as part of a broader inflammatory profile in COVID-19 patients.

The present study evaluated the correlation between serum ferritin levels and disease severity in patients diagnosed with COVID-19. Among the 80 patients included, the age distribution showed a predominance in the 40–59 years category, with a slight male majority (45 males, 35 females). A significant proportion of patients had comorbidities such as diabetes and hypertension, both of which are known risk factors for severe COVID-19. These baseline characteristics are consistent with findings from Zhou et al., who reported that older age and male sex, along with comorbidities like diabetes and hypertension, were associated with increased risk of severe outcomes in COVID-19 patients ¹³. Similarly, Richardson et al. found that the majority of hospitalized COVID-19 patients were male and had underlying health conditions, reinforcing the importance of demographic and comorbidity profiling in disease assessment ¹⁴.

The clinical presentation of patients revealed that fever, cough, and shortness of breath were the most frequently reported symptoms. Fatigue and sore throat were also common, while a minority remained asymptomatic. These symptom patterns align with the clinical spectrum described by Guan et al., who observed that fever and cough were the most prevalent symptoms among COVID-19 patients in China ¹⁵. Huang et al. also reported similar symptomatology, with respiratory symptoms being predominant, further supporting the findings of the present study ¹⁶.

A key finding of this study was the progressive elevation in serum ferritin levels with increasing disease severity. Patients categorized as having mild, moderate, and severe disease showed a clear upward trend in mean ferritin values, reinforcing the role of ferritin as a potential biomarker for disease progression. This observation is corroborated by Chen et al., who found that elevated ferritin levels were strongly associated with severe and critical cases of COVID-19 ¹⁷. Likewise, a meta-analysis by Cheng et al. demonstrated that higher ferritin levels were consistently observed in patients with severe disease compared to those with milder forms ¹⁸.

Further analysis revealed that male patients consistently exhibited higher serum ferritin levels across all severity categories when compared to females. This observation may be attributed to biological differences in baseline ferritin levels, hormonal influences, and immune response variations between sexes. These findings are in agreement with the study by Scully et al., which highlighted sex differences in immune response and inflammatory marker expression, including ferritin, in COVID-19 patients ¹⁹. Additionally, a study by Peckham et al. reported that men are more likely to experience severe COVID-19 and elevated inflammatory markers, supporting the sex-specific patterns seen in the present study ²⁰.

Additionally, serum ferritin levels were positively correlated with other inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and D-Dimer. The rise in these markers alongside ferritin from mild to severe disease stages indicates a synchronized inflammatory response, characteristic of the cytokine storm seen in severe COVID-19. This finding is supported by the work of Ruan et al., who observed that elevated ferritin, CRP, and IL-6 levels were associated with poor outcomes and hyperinflammatory states in COVID-19 ²¹. Similarly, Herold et al. demonstrated that IL-6 and ferritin levels could serve as predictors of respiratory failure, reinforcing the interconnected nature of these biomarkers ²².

In clinical practice, the inclusion of serum ferritin as part of the initial assessment panel could aid in risk stratification, especially in resource-limited settings where comprehensive inflammatory profiling may not be feasible. By identifying patients with elevated ferritin early, healthcare providers may be better equipped to anticipate worsening outcomes and intervene accordingly. This approach is supported by the recommendations of the World Health Organization and several clinical guidelines, which advocate for the use of ferritin and other inflammatory markers in the assessment of COVID-19 severity ^23,24.

Despite the valuable insights gained, this study is limited by its relatively small sample size and single-center design, which may affect generalizability. Future research involving larger, multicentric cohorts is needed to validate these findings. Moreover, exploring the mechanistic role of ferritin in COVID-19 pathophysiology and its interaction with host factors such as gender and comorbidities could further enhance our understanding and guide targeted therapeutic strategies.

This study demonstrates a significant positive correlation between serum ferritin levels and disease severity in patients with COVID-19. Elevated ferritin was consistently associated with more severe clinical presentations and higher levels of other inflammatory markers, underscoring its role as a valuable biomarker for early risk stratification and monitoring disease progression. The findings also highlight the influence of demographic factors, such as age and sex, and comorbidities on ferritin levels and clinical outcomes. Incorporating serum ferritin measurement into routine assessment could facilitate timely identification of patients at risk for clinical deterioration, particularly in resource-limited settings. However, the study’s single-center design and limited sample size warrant caution in generalizing these results. Further large-scale, multicentric research is needed to validate these observations and explore the mechanistic role of ferritin in COVID-19 pathophysiology. Overall, serum ferritin is a promising marker that can enhance clinical decision-making in the management of COVID-19.

1. World Health Organization. Coronavirus disease (COVID-19) pandemic. [Internet]. 2020. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
2. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-20.
3. Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017;29(9):401-9.
4. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4.
5. Shoenfeld Y. Corona (COVID-19) time musings: Our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning. Autoimmun Rev. 2020;19(6):102538.
6. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, 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):1054-62.
7. Cheng L, Li H, Li L, Liu C, Yan S, Chen H, et al. Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. J Clin Lab Anal. 2020;34(10):e23618.
8. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295.
9. Colafrancesco S, Alessandri C, Conti F, Priori R. COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? Autoimmun Rev. 2020;19(7):102573.
10. Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D’Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013;11:185.
11. Scully EP, Haverfield J, Ursin RL, Tannenbaum C, Klein SL. Considering how biological sex impacts immune responses and COVID-19 outcomes. Nat Rev Immunol. 2020;20(7):442-7.
12. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58(7):1021-8.
13. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, 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):1054-62.
14. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020;323(20):2052-9.
15. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-20.
16. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
17. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-9.
18. Cheng L, Li H, Li L, Liu C, Yan S, Chen H, et al. Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. J Clin Lab Anal. 2020;34(10):e23618.
19. Scully EP, Haverfield J, Ursin RL, Tannenbaum C, Klein SL. Considering how biological sex impacts immune responses and COVID-19 outcomes. Nat Rev Immunol. 2020;20(7):442-7.
20. Peckham H, de Gruijter NM, Raine C, Radziszewska A, Ciurtin C, Wedderburn LR, et al. Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. Nat Commun. 2020;11(1):6317.
21. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846-8.
22. Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146(1):128-36.e4.
23. World Health Organization. Clinical management of COVID-19: interim guidance, 27 May 2020. Geneva: WHO; 2020.
24. National Institutes of Health. COVID-19 Treatment Guidelines. [Internet]. Available from: https://www.covid19treatmentguidelines.nih.gov/ (Accessed June 2025).