Predictive Biomarkers in Hypertensive COVID-19 Patients: Systematic Review of Ferritin and D-Dimer Levels
Abstract
Inflammation and hypercoagulability have been identified as key factors in severe COVID-19, particularly in hospitalized patients with hypertension. Elevated ferritin and D-dimer levels are often associated with worse outcomes, but their effectiveness has not been extensively studied. This study aimed to systematically evaluate the prognostic utility of ferritin and D-dimer in hypertensive COVID-19 patients to determine their individual and combined roles in predicting disease severity and clinical outcomes. The scientific novelty of this work lies in its direct comparison of ferritin and D-dimer, two widely implicated but rarely juxtaposed biomarkers, in the context of hypertensive COVID-19 patients. This review provides a comprehensive analysis of their prognostic value, offering insights into the interplay between hyperinflammation and hypercoagulability in the COVID-19 pathophysiology. This novel perspective could pave the way for biomarker-driven therapeutic interventions for this vulnerable patient population. Scopus, ScienceDirect, Web of Science, and PubMed databases were searched to identify studies published between 2019 and 2023. This systematic review included 25 original research articles from an initial pool of 1748 records. All selected studies reported the association between ferritin and D-dimer levels and morbidity and mortality in hospitalized hypertensive patients with severe COVID-19. The majority of the included studies showed that elevated ferritin levels were strongly associated with an increased risk of serious outcomes, including ICU admission and mortality. In comparison, although D-dimer levels were also significant predictors, ferritin levels proved to be a more consistent marker. In addition, the prognostic value of these biomarkers was higher in older patients and those with additional comorbidities, suggesting a critical role in risk stratification. Our systematic analysis concluded that elevated ferritin levels are a robust predictor of morbidity and mortality in hospitalized hypertensive patients with severe COVID-19, often outperforming D-dimer levels. This increased risk is influenced by patient age and comorbidities, highlighting the need for further research to optimize clinical management strategies.
Keywords: COVID-19; hypertension; ferritin; D-dimer; morbimortality; risk stratification
Full Text:
PDFReferences
MEHANNA O., EL ASKARY A., ALI E., EL ESAWY B., FATHALLA T., & GHARIB A.F. Impact of Obesity and Its Associated Comorbid Conditions on COVID-19 Presentation. Diabetes, Metabolic Syndrome and Obesity, 2021, 14: 409–4015. https://doi.org/10.2147/DMSO.S287779
LÓPEZ MUÑOZ D.F., SUÁREZ JARAMILLO L.A., GULLOSO PEDROZO L., GÓMEZ GUERRERO S.M., SÁNCHEZ MONCAYO A., & GIRALDO OSPINA B. Evaluación de la seroconversión de anticuerpos contra SARS-COV-2. Magna Scientia UCEVA, 2022, 2(1): 52-59. https://doi.org/10.54502/msuceva.v2n1a5
PONTI G., MACCAFERRI M., RUINI C., TOMASI A., & OZBEN T. Biomarkers associated with COVID-19 disease progression. Critical Reviews in Clinical Laboratory Sciences, 2020, 57: 389–399. https://doi.org/10.1080/10408363.2020.1770685
WHITE-DZURO G., GIBSON L. E., ZAZZERON L., WHITE-DZURO C., SULLIVAN Z., DIIORIO D. A., LOW S. A., CHANG M. G., & BITTNER E. A. Multisystem effects of COVID-19: a concise review for practitioners. Postgraduate Medicine, 2021 133(1): 20–27. https://doi.org/10.1080/00325481.2020.1823094
TURAN O., ARPINAR YIGITBAS B., TURAN P.A., & MIRICI A. Clinical characteristics and outcomes of hospitalized COVID-19 patients with COPD. Expert Review of Respiratory Medicine, 2021, 15(8): 1069–1076. https://doi.org/10.1080/17476348.2021.1923484
ARÉVALO-LORIDO J. C., CARRETERO-GÓMEZ J., CASAS-ROJO J. M., ANTÓN-SANTOS J. M., MELERO-BERMEJO J. A., LÓPEZ-CARMONA M. D., … & GÓMEZ-HUELGAS R. The importance of association of comorbidities on COVID-19 outcomes: a machine learning approach. Current Medical Research and Opinion, 2022, 38(4): 501–510. https://doi.org/10.1080/03007995.2022.2029382
MERAD M., & MARTIN J.C. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nature Reviews. Immunology, 2020, 20(6): 355–362. https://doi.org/10.1038/s41577-020-0331-4
HUYUT M.T., & HUYUT Z. Effect of ferritin, INR, and D-dimer immunological parameters levels as predictors of COVID-19 mortality: A strong prediction with the decision trees. Heliyon, 2023, 9: e14015. https://doi.org/10.1016/j.heliyon.2023.e14015
ZHAO X., ZHOU Y., ZHANG Y., & ZHANG Y. Ferritin: Significance in viral infections. Reviews in Medical Virology, 2024, 34(2): e2531. https://doi.org/10.1002/rmv.2531
HADDAWAY N.R., PAGE M.J., PRITCHARD C.C., & MCGUINNESS L.A. PRISMA2020: An R package and Shiny app for producing PRISMA 2020‐compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Systematic Reviews, 2022, 18(2): e1230. https://doi.org/10.1002/cl2.1230
ECHEVERRI-CATAÑO L., GIRALDO-OSPINA B., VARGAS ARBOLEDA D., CASTAÑEDA MEJÍA C., & GARCÉS AGUDELO N. Ferritin as a predictor of morbidity and mortality in hospitalized hypertensive patients with severe covid diagnosis compared with d-dimer values: systematic review and meta-analysis. PROSPERO, 2023, CRD42023440378. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023440378
HERNÁNDEZ-MORALES M. DEL R., MALDONADO-CASTAÑEDA S., MANCILLA-HERNÁNDEZ E., AMARO-ZARATE I., AGUIRRE-BARBOSA M., & NAZARALA-SANCHEZ S. Frequency of clinical characteristics and factors associated with mortality in patients hospitalized for COVID-19 in Puebla, Mexico. Revista Alergia México, 2022, 69(2): 67–71. https://doi.org/10.29262/ram.v69i2.1146
ASHKTORAB H., PIZUORNO A., ADELEYE F., LAIYEMO A., DALIVAND M. M., ADULI F., SHERIF Z. A., OSKROCHI G., ANGESOM K., OPPONG-TWENE P., CHALLA S. R., OKORIE N., MOON E. S., ROMOS E., JONES-WONNI B., KONE A. M., RANKINE S., THRIFT C., SCHOLES D., EKWUNAZU, C., … & BRIM H. Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans. BMC Infectious Diseases, 2022, 22(1): 552. https://doi.org/10.1186/s12879-022-07520-1
PATIL S., GONDHALI G., & ACHARYA A. “Serial ferritin titer” monitoring in COVID-19 pneumonia: valuable inflammatory marker in assessment of severity and predicting early lung fibrosis — prospective, multicentric, observational, and interventional study in tertiary care setting in India. Egyptian Journal of Internal Medicine, 2022, 34(1): 75. https://doi.org/10.1186/s43162-022-00163-3
SUDAREV V. V., DOLOTOVA S. M., BUKHALOVICH S. M., BAZHENOV S. V., RYZHYKAU Y. L., UVERSKY V. N., BONDAREV N. A., OSIPOV S. D., MIKHAILOV A. E., KUKLINA D. D., MURUGOVA T. N., MANUKHOV I. V., ROGACHEV A. V., GORDELIY V. I., GUSHCHIN I. Y., KUKLIN A. I., & VLASOV A. V. Ferritin self-assembly, structure, function, and biotechnological applications. International Journal of Biological Macromolecules, 2023, 224: 319–343. https://doi.org/10.1016/j.ijbiomac.2022.10.126
MAHROUM N., ALGHORY A., KIYAK Z., ALWANI A., SEIDA R., ALRAIS M., & SHOENFELD, Y. Ferritin – from iron, through inflammation and autoimmunity, to COVID-19. Journal of Autoimmunity, 2022, 126: 102778. https://doi.org/10.1016/j.jaut.2021.102778
KAPPERT K., JAHIĆ A., & TAUBER R. Assessment of serum ferritin as a biomarker in COVID-19: bystander or participant? Insights by comparison with other infectious and non-infectious diseases. Biomarkers, 2020, 25: 616–625. https://doi.org/10.1080/1354750X.2020.1797880
KAUSHAL, K., KAUR, H., SARMA, P., BHATTACHARYYA, A., SHARMA, D. J., PRAJAPAT, M., PATHAK, M., KOTHARI, A., KUMAR, S., RANA, S., KAUR, M., PRAKASH, A., MIRZA, A. A., PANDA, P. K., VIVEKANANDAN, S., OMAR, B. J., MEDHI, B., & NAITHANI, M. Serum ferritin as a predictive biomarker in COVID-19. A systematic review, meta-analysis and meta-regression analysis. Journal of Critical Care, 2022, 67: 172–181. https://doi.org/10.1016/j.jcrc.2021.09.023
RUSCH J.A., VAN DER WESTHUIZEN D.J., GILL R.S., & LOUW V.J. Diagnosing iron deficiency: Controversies and novel metrics. Best Practice & Research Clinical Anaesthesiology, 2023, 37(4): 451–467. https://doi.org/10.1016/j.bpa.2023.11.001
KONYA P, DEMIRTÜRK N, KORKMAZ D, TÜNAY H, KOŞAR EB. Evaluation of clinical and laboratory characteristics and factors affecting mortality in 500 hospitalized COVID-19 patients. Saudi Medical Journal, 2022, 43(11): 1254–1259. https://doi.org/10.15537/smj.2022.43.11.20220641
KARA Ö., KARA M., AKIN M.E., & ÖZÇAKAR L. Grip strength as a predictor of disease severity in hospitalized COVID-19 patients. Heart & Lung: The Journal of Critical Care, 2021, 50(6): 743–747. https://doi.org/10.1016/j.hrtlng.2021.06.005
RADKHAH H., MANSOURI E. S., RAHIMIPOUR ANARAKI S., GHOLIZADEH MESGARHA M., SHEIKHY A., KHADEMBASHIRI M. M., KHADEMBASHIRI M. A., ESLAMI M., MAHMOODI T., INANLOO B., & POUR MOHAMMAD A. Predictive value of hematological indices on incidence and severity of pulmonary embolism in COVID-19 patients. Immunity, Inflammation and Disease, 2023, 11(9), e1012. https://doi.org/10.1002/iid3.1012
MUHAMMAD R., OGUNTI R., AHMAD B., MUNAWAR M., DONALDSON S., SUMON M., KIBREAB A., THOMAS A. N., & MEHARI A. Clinical Characteristics and Predictors of Mortality in Minority Patients Hospitalized with COVID-19 Infection. Journal of Racial and Ethnic Health Disparities, 2022, 9(1): 335–345. https://doi.org/10.1007/s40615-020-00961-x
VIZCAYCHIPI M. P., SHOVLIN C. L., MCCARTHY A., GODFREY A., PATEL S., SHAH P. L., HAYES M., KEAYS R. T., BEVERIDGE I., & DAVIES G. Increase in COVID-19 inpatient survival following detection of Thromboembolic and Cytokine storm risk from the point of admission to hospital by a near real time Traffic-light System (TraCe-Tic). Brazilian Journal of Infectious Diseases, 2020, 24: 412–421. https://doi.org/10.1016/j.bjid.2020.07.010
PARA O., CARUSO L., PESTELLI G., TANGIANU F., CARRARA D., MADDALUNI L., TAMBURELLO A., CASTELNOVO L., FEDI G., GUIDI S., PESTELLI C., PENNELLA B., CIARAMBINO T., NOZZOLI C., & DENTALI F. Ferritin as prognostic marker in COVID-19: the FerVid study. Postgraduate Medicine, 2022, 134: 58–63. https://doi.org/10.1080/00325481.2021.1990091
KESKI H. Hematological and Inflammatory Parameters to Predict the Prognosis in COVID-19. Indian Journal of Hematology and Blood Transfusion, 2021, 37: 534–42. https://doi.org/10.1007/s12288-021-01407-y
KESMEZ CAN F., ALAY H., ALBAYRAK A., ÖZDEN K., YILMAZ S., ÖZTÜRK N., ÖZKURT Z., PARLAK E., TEKIN E., & KOÇAK A. O. The Effects of Laboratory Parameters on the Prognosis of COVID-19. Eurasian Journal of Medicine, 2022, 54(3): 242–247. https://doi.org/10.5152/eurasianjmed.2022.22031
CASAS-ROJO J.M., ANTÓN-SANTOS J.M., MILLÁN-NÚÑEZ-CORTÉS J., LUMBRERAS-BERMEJO C., RAMOS-RINCÓN J.M., ROY-VALLEJO E., … EN NOMBRE DEL GRUPO SEMI-COVID-19 NETWORK (2020). Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Registry. Revista Clínica Española, 2020, 220(8): 480-494. https://doi.org/10.1016/j.rce.2020.07.003
SHAKAROUN D.A., LAZAR M.H., HOROWITZ J.C., & JENNINGS J.H. Serum Ferritin as a Predictor of Outcomes in Hospitalized Patients with Covid-19 Pneumonia. Journal of Intensive Care Medicine, 2023, 38(1): 21–26. https://doi.org/10.1177/08850666221113252
ABBATTISTA M., CIAVARELLA A., CAPECCHI M., TANTARDINI F., GRAMEGNA A., LOMBARDI R., SCARAMELLINI N., PEYVANDI F., & MARTINELLI I. Risk factors for mortality in hospitalized patients with COVID-19: a study in Milan, Italy. Infectious Diseases, 2021, 53: 226–229. https://doi.org/10.1080/23744235.2020.1859131
ALTUNTAS M., YILMAZ H., & GUNER A.E. Evaluation of patients with COVID-19 diagnosis for chronic diseases. Virology Journal, 2021, 18(1): 57. https://doi.org/10.1186/s12985-021-01524-0
ZAYED N.E., ABBAS A., & LUTFY S.M. Criteria and potential predictors of severity in patients with COVID-19. The Egyptian Journal of Bronchology, 2022, 16(1): 11. https://doi.org/10.1186/s43168-022-00116-y
DONG G., DU Z., ZHU J., GUO Y., GAO W., GUO W., WANG T., & JIANG B. The clinical characteristics and prognosis of COVID-19 patients with comorbidities: a retrospective analysis of the infection peak in Wuhan. Annals of Translational Medicine, 2021, 9(4): 280. https://doi.org/10.21037/atm-20-4052
ETKIN Y., CONWAY A. M., SILPE J., QATO K., CARROCCIO A., MANVAR-SINGH P., GIANGOLA G., DEITCH J. S., DAVILA-SANTINI L., SCHOR J. A., SINGH K., MUSSA F. F., & LANDIS G. S. Acute Arterial Thromboembolism in Patients with COVID-19 in the New York City Area. Annals of Vascular Surgery, 2021, 70: 290–294. https://doi.org/10.1016/j.avsg.2020.08.085
EL-KHATTAB S.O., ABDELHAMID A.E.E., ABDALLA IBRAHIM W., YOUSEF ELSHERIF A.I., & KHALIL G.M. C-reactive protein as an early marker of severity and outcome in patients with SARS-CoV-2 infection. Egyptian Journal of Anaesthesia, 2023, 39(1): 95–99.
https://doi.org/10.1080/11101849.2023.2171545
ELENI M., EVANGELIA M., ELEFTHERIA K., VASILIOS V., VANA S., VISSARIA S., EVANGELOS B., & IOANNIS K. Clinical features and outcomes of hospitalized COVID-19 patients in a low burden region. Pathogens and Global Health, 2021, 115(4): 243–249. https://doi.org/10.1080/20477724.2021.1893485
Refbacks
- There are currently no refbacks.
