Potential Role of Ferritin Levels in Distinguish the Severity and Predict the Outcome of COVID-19 Patients
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Ferritin is a key mediator of immune dysregulation through its direct pro-inflammatory effects, which contribute to inflammatory cytokine storms and tissue damage. This study aims to analyze ferritin roles in distinguish the severity and predict the outcome of COVID-19 patients. An observational analytic study, using a cross-sectional design, enrolled 142 patients which subsequently divided into a non-severe (mild to moderate cases) and a severe (severe to critically ill cases) group. The levels of ferritin was examined using Enzyme Immunoassay Test Kit on the first day patients was hospitalized. Mann Whitney test was used to analyze the correlation between ferritin levels with severity and outcome of COVID-19 patients. The median of ferritin level was higher in the severe group (1532.1 ng/ml, SD= 1715.552) compared to non-severe group (413.3 ng/ml, SD= 459.804) with a statistically significant difference (p< 0.001), cut off point of 865.1 ng/ml, sensitivity of 86.96% (95% CI: 76.68%–93.86%), and specificity of 87.67% (95% CI: 77.88%–94.20%). Ferritin levels were also higher in non-survivors (1496.55 ng/ml, SD = 1798.677) than in survivors (662.05 ng/ml, SD = 1293.026), with a significant difference (p < 0.001), cut off point of 1032.85 ng/ml, sensitivity of 63.33% (95% CI: 43.86% to 80.07%), and specificity of 63.39% (95% CI: 53.76% to 72.29%). This results showed that ferritin levels may not good enough to predict the outcomes, with Contingency coefficient of 0.244 that showed a very weak correlation. The baseline ferritin levels at admission was closely related to the severity of COVID-19, thus it may be considered a potential biomarker for assessing disease severity. However, ferritin levels appear to be insufficiently accurate for predicting clinical outcomes in COVID-19 patients.
Carcillo, J. A., Kernan, K. K., Horvat, C. M., Simon, D. W., & Aneja, R. K. (2020). Why and How Is Hyperferritinemic Sepsis Different From Sepsis Without Hyperferritinemia?*. Pediatric Critical Care Medicine, 21(5), 509–512. https://doi.org/10.1097/PCC.0000000000002285
Chen, G., Wu, D., Guo, W., Cao, Y., Huang, D., Wang, H., Wang, T., Zhang, X., Chen, H., Yu, H., Zhang, X., Zhang, M., Wu, S., Song, J., Chen, T., Han, M., Li, S., Luo, X., Zhao, J., & Ning, Q. (2020). Clinical and immunological features of severe and moderate coronavirus disease 2019. Journal of Clinical Investigation, 130(5), 2620–2629. https://doi.org/10.1172/JCI137244
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J., Yu, T., Zhang, X., & Zhang, L. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet, 395(10223), 507–513. https://doi.org/10.1016/S0140-6736(20)30211-7
Cheng, L., Li, H., Li, L., Liu, C., Yan, S., Chen, H., & Li, Y. (2020). Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis. Journal of Clinical Laboratory Analysis, 34(10). https://doi.org/10.1002/jcla.23618
Dahan, S., Segal, G., Katz, I., Hellou, T., Tietel, M., Bryk, G., Amital, H., Shoenfeld, Y., & Dagan, A. (2020). Ferritin as a Marker of Severity in COVID-19 Patients: A Fatal Correlation. The Israel Medical Association Journal : IMAJ, 22(8), 494–500. http://europepmc.org/abstract/MED/33236582
Feld, J., Tremblay, D., Thibaud, S., Kessler, A., & Naymagon, L. (2020). Ferritin levels in patients with COVID‐19: A poor predictor of mortality and hemophagocytic lymphohistiocytosis. International Journal of Laboratory Hematology, 42(6), 773–779. https://doi.org/10.1111/ijlh.13309
Grant, M. C., Geoghegan, L., Arbyn, M., Mohammed, Z., McGuinness, L., Clarke, E. L., & Wade, R. G. (2020). The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLOS ONE, 15(6), e0234765. https://doi.org/10.1371/journal.pone.0234765
Guan, W., Ni, Z., Hu, Y., Liang, W., Ou, C., He, J., Liu, L., Shan, H., Lei, C., Hui, D. S. C., Du, B., Li, L., Zeng, G., Yuen, K.-Y., Chen, R., Tang, C., Wang, T., Chen, P., Xiang, J., … Zhong, N. (2020). Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine, 382(18), 1708–1720. https://doi.org/10.1056/NEJMoa2002032
Huang, I., Pranata, R., Lim, M. A., Oehadian, A., & Alisjahbana, B. (2020). C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Therapeutic Advances in Respiratory Disease, 14. https://doi.org/10.1177/1753466620937175
Jin, J.-M., Bai, P., He, W., Wu, F., Liu, X.-F., Han, D.-M., Liu, S., & Yang, J.-K. (2020). Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Frontiers in Public Health, 8. https://doi.org/10.3389/fpubh.2020.00152
Kernan, K. F., & Carcillo, J. A. (2017). Hyperferritinemia and inflammation. International Immunology, 29(9), 401–409. https://doi.org/10.1093/intimm/dxx031
Kong, M., Zhang, H., Cao, X., Mao, X., & Lu, Z. (2020). Higher level of neutrophil-to-lymphocyte is associated with severe COVID-19. Epidemiology and Infection, 148, e139. https://doi.org/10.1017/S0950268820001557
Li, Y., Hu, Y., Yu, J., & Ma, T. (2020). Retrospective analysis of laboratory testing in 54 patients with severe- or critical-type 2019 novel coronavirus pneumonia. Laboratory Investigation, 100(6), 794–800. https://doi.org/10.1038/s41374-020-0431-6
Lin, Z., Long, F., Yang, Y., Chen, X., Xu, L., & Yang, M. (2020). Serum ferritin as an independent risk factor for severity in COVID-19 patients. Journal of Infection, 81(4), 647–679. https://doi.org/10.1016/j.jinf.2020.06.053
Liu, T., Zhang, J., Yang, Y., Ma, H., Li, Z., Zhang, J., Cheng, J., Zhang, X., Zhao, Y., Xia, Z., Zhang, L., Wu, G., & Yi, J. (2020). The role of interleukin‐6 in monitoring severe case of coronavirus disease 2019. EMBO Molecular Medicine, 12(7). https://doi.org/10.15252/emmm.202012421
Luo, L., Fu, M., Li, Y., Hu, S., Luo, J., Chen, Z., Yu, J., Li, W., Dong, R., Yang, Y., Tu, L., & Xu, X. (2020). The potential association between common comorbidities and severity and mortality of coronavirus disease 2019: A pooled analysis. Clinical Cardiology, 43(12), 1478–1493. https://doi.org/10.1002/clc.23465
Paudel, S. S. (2020). A meta-analysis of 2019 novel corona virus patient clinical characteristics and comorbidities. https://doi.org/10.21203/rs.3.rs-21831/v1
Perricone, C., Bartoloni, E., Bursi, R., Cafaro, G., Guidelli, G. M., Shoenfeld, Y., & Gerli, R. (2020). COVID-19 as part of the hyperferritinemic syndromes: the role of iron depletion therapy. Immunologic Research, 68(4), 213–224. https://doi.org/10.1007/s12026-020-09145-5
Shi, Y., Yu, X., Zhao, H., Wang, H., Zhao, R., & Sheng, J. (2020). Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan. Critical Care, 24(1), 108. https://doi.org/10.1186/s13054-020-2833-7
Torti, F. M., & Torti, S. V. (2002). Regulation of ferritin genes and protein. Blood, 99(10), 3505–3516. https://doi.org/10.1182/blood.V99.10.3505
Vargas-Vargas, M., & Cortés-Rojo, C. (2020). Ferritin levels and COVID-19. Revista Panamericana de Salud Pública, 44, 1. https://doi.org/10.26633/RPSP.2020.72
Velavan, T. P., & Meyer, C. G. (2020). Mild versus severe COVID-19: Laboratory markers. International Journal of Infectious Diseases, 95, 304–307. https://doi.org/10.1016/j.ijid.2020.04.061
World Health Organization (WHO). 2020. Clinical management of COVID-19. interim guidance. Available from: https://www.who.int/ publications-detail/clinical-management-of-severe- acute-respiratory- infection-when-novel-coronavirus-(ncov)-infection-is- suspected. accessed 25 Oct 2020.
WHO. (2021a). Coronavirus Disease 2019 (COVID-19) World Health Organization Indonesia 27 January 2021 Coronavirus Disease 2019 (COVID-19) Coronavirus Disease 2019 (COVID-19) Situation Report - 40.
WHO. (2021b). WHO Coronavirus Disease (COVID-19) Dashboard.
Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., Huang, H., Zhang, L., Zhou, X., Du, C., Zhang, Y., Song, J., Wang, S., Chao, Y., Yang, Z., Xu, J., Zhou, X., Chen, D., Xiong, W., … Song, Y. (2020). Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Internal Medicine, 180(7), 934. https://doi.org/10.1001/jamainternmed.2020.0994
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., Guan, L., Wei, Y., Li, H., Wu, X., Xu, J., Tu, S., Zhang, Y., Chen, H., & Cao, B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet, 395(10229), 1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3
