COVİD-19’lu İleri Yaşlı Hastalarda Hiperferritinemi Hastalık Şiddeti Yönünden Güvenilir midir?

Year 2023, , 649 - 655, 31.12.2023

Muhammet Özbilen , Şeyda Tuba Savrun , Celali Kurt , Yeliz Kaşko Arıcı

https://doi.org/10.54005/geneltip.1199803

Abstract

Amaç: Covid-19’a yakalanmış yaşlı hastalarda ferritin düzeylerinin çeşitli hastalık şiddeti göstergelerinden daha üstün olup olmadığını belirlemek.
Yöntem: Eylül 2020 ile Ocak 2021 tarihleri arasında Covid-19 şüphesi veya tanısı ile Ordu Üniversitesi Eğitim ve Araştırma Hastanesi acil servisine başvuran hastalar retrospektif ve kesitsel olarak incelendi. Temel dahil etme kriterleri hastaların 18 yaş ve üzeri olması ve glomerüler filtrasyon hızının 30 ml/ dk/1,73 m2 idi. Hastalara ait kronik hastalık öyküsü, mortalite durumu, hemogram, kan gazı, ferritin, c-reaktif protein ve vital bulgularına ilişkin veriler ile Covid-19 tanısı için yapılan test ve tetkiklere ilişkin veriler kaydedilmiştir. Veri seti iki bölüme ayrılmıştır: <65 yaş ≥65 yaş.
Bulgular: Kriterleri karşılayan 416 hasta çalışmaya dahil edilmiştir. Toplam hasta sayısının 321’i 65 yaşın altında, 95’i ise 65 yaş ve üzerindeydi. Yaş ortalamaları 65 yaş altı grup için 42.50±12.73, yaşlı hasta grubu için 77.89±7.34 idi. Ortalama ferritin düzeyi, 65 yaş ve üzeri hastalarda (249.59±261.45 ng/mL) 65 yaş altı hastalara (169.76±210.44 ng/mL) göre anlamlı düzeyde yüksekti (p=0.001). Ferritin düzeyleri sadece mortalite yönünden iki grup arasında farklılaştı (p<0.037). Yaşlı hastalara ait mortal seyreden alt grupta ferritine ait AUC değeri 0.700 (%95 GA, 0.482-0.919) ve cut-off değeri 231.55 ng/mL idi (duyarlılık=%67.7, özgüllük=%67.4) ve tüm biyobelirteçler içinde yalnızca ferritin seviyeleri anlamlı olarak farklılaşma gösterdi.
Sonuç: C-reaktif protein de dahil olmak üzere iyi bilinen şiddetli hastalık serum belirteçleri, yaşlı hastaların Covid-19 yönünden mortalite tahmininde ferritin kadar değerli değildir. Ferritin, yaşlı Covid-19 hastalarında en güçlü mortalite belirleyicisi olabilir.

Keywords

Covid-19, yaş, yaşlı, ferritin, hiperferritinemi, hastalık şiddeti, mortalite

Is Hyperferritinemia Reliable in Determining the Severity of COVID-19 in Older Patients?

Abstract

Aim: To determine whether ferritin levels among elderly patients inflicted with Covid-19 are superior to several types of disease severity indicators.
Methods: A retrospective and cross-sectional analysis was conducted on patients who were admitted to the emergency department of Ordu University Training and Research Hospital between September 2020 and January 2021, with a suspected or confirmed diagnosis of Covid-19. Patients had to be 18 years of age or older and have a glomerular filtration rate greater than 30 ml/min/1.73 m2 in order to meet the basic inclusion criteria. In addition, the data pertaining to the patients’ chronic diseases, mortality status, hemogram, blood gas, ferritin, c-reactive protein, and vital signs were recorded alongside the information regarding the tests and examinations conducted for the diagnosis of Covid-19. The data set is divided into two parts: <65 years ≥65 years.
Results: Four hundred sixteen patients were identified as meeting the criteria for the study. Out of the total number of patients, 321 were under the age of 65, while 95 were 65 years of age or older. The under-65 group’s mean age was 42.50±12.73 while the older group was 77.89±7.34 years. The mean ferritin of patients 65 and older (249.59±261.45 ng/mL) was significantly more than the patients under 65 (169.76±210.44 ng/mL) (p=0.001). Only mortality differed between older and younger patients (p=0.049). The AUC value of ferritin in older patients was 0.700 (95% CI, 0.482-0.919), and the cut-off value was 231.55 ng/mL in the mortal group (sensitivity=66.7%, specificity=67.4%). Only ferritin levels were significant in older patients’ AUC scores of mortality stats among the other biomedical markers.
Conclusions: Some well-known severe disease blood markers, including c-reactive protein, are not as significant as ferritin in older patient mortality ROC curve analyses. Ferritin may be the strongest mortality predictor in older Covid-19 patients.

Keywords

Covid-19, age, older, ferritin, illness severity, hyperferritinemia, mortality

References

• 1. Yusof W, Irekeola AA, Wada Y, Engku Abd Rahman ENS, Ahmed N, Musa N, et al. A Global Mutational Profile of SARS-CoV-2: A Systematic Review and Meta-Analysis of 368,316 COVID-19 Patients. Life (Basel). 2021 Nov 11;11(11):1224.
• 2. WHO Coronavirus (COVID-19) Dashboard [Internet]. [cited 2022 Sep 23]. Available from: https://covid19.who.int
• 3. Ginaldi L, De Martinis M, D’Ostilio A, Marini L, Loreto MF, Quaglino D. Immunological changes in the elderly. Aging (Milano). 1999 Oct;11(5):281–6.
• 4. Mohamadi M, Goodarzi A, Aryannejad A, Fattahi N, Alizadeh-Khoei M, Miri S, et al. Geriatric challenges in the new coronavirus disease-19 (COVID-19) pandemic: A systematic review. Med J Islam Repub Iran. 2020 Sep 17;34:123.
• 5. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020;34:101623.
• 6. 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. 130(5):2620–9.
• 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 Oct 19;34(10):e23618.
• 8. Huang I, Pranata R, Lim MA, Oehadian A, Alisjahbana B. C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Ther Adv Respir Dis. 2020 Jul 2;14:1753466620937175.
• 9. Prokop M, van Everdingen W, van Rees Vellinga T, Quarles van Ufford H, Stöger L, Beenen L, et al. CO-RADS: A Categorical CT Assessment Scheme for Patients Suspected of Having COVID-19-Definition and Evaluation. Radiology. 2020 Aug;296(2):E97–104.
• 10. Mahroum N, Alghory A, Kiyak Z, Alwani A, Seida R, Alrais M, et al. Ferritin – from iron, through inflammation and autoimmunity, to COVID-19. J Autoimmun. 2022 Jan;126:102778.
• 11. Kawamata R, Yokoyama K, Sato M, Goto M, Nozaki Y, Takagi T, et al. Utility of serum ferritin and lactate dehydrogenase as surrogate markers for steroid therapy for Mycoplasma pneumoniae pneumonia. J Infect Chemother. 2015 Nov;21(11):783–9.
• 12. Cunha BA. Highly elevated serum ferritin levels as a diagnostic marker for Legionella pneumonia. Clin Infect Dis. 2008 Jun 1;46(11):1789–91.
• 13. Vardeny O, Madjid M, Solomon SD. Endemic and Pandemic Viral Illnesses and Cardiovascular Disease: Influenza and COVID-19. In: Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine [Internet]. Elsevier Inc.; 2022 [cited 2022 Jul 6]. p. 1751–65. Available from: https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323722193000943?scrollTo=%23hl0000790
• 14. Ruscitti P, Di Cola I, Di Muzio C, Italiano N, Ursini F, Giacomelli R, et al. Expanding the spectrum of the hyperferritinemic syndrome, from pathogenic mechanisms to clinical observations, and therapeutic implications. Autoimmun Rev. 2022 Jul;21(7):103114.
• 15. Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017 Nov;29(9):401–9.
• 16. Ahmed S, Ansar Ahmed Z, Siddiqui I, Haroon Rashid N, Mansoor M, Jafri L. Evaluation of serum ferritin for prediction of severity and mortality in COVID-19- A cross sectional study. Annals of Medicine and Surgery. 2021 Mar 1;63:102163.
• 17. Feld J, Tremblay D, Thibaud S, Kessler A, Naymagon L. Ferritin levels in patients with COVID-19: A poor predictor of mortality and hemophagocytic lymphohistiocytosis. International Journal of Laboratory Hematology. 2020;42(6):773–9.
• 18. Tural Onur S, Altın S, Sokucu SN, Fikri Bİ, Barça T, Bolat E, et al. Could ferritin level be an indicator of COVID-19 disease mortality? J Med Virol. 2021 Mar;93(3):1672–7.
• 19. Rasyid H, Sangkereng A, Harjianti T, Soetjipto AS. Impact of age to ferritin and neutrophil-lymphocyte ratio as biomarkers for intensive care requirement and mortality risk in COVID-19 patients in Makassar, Indonesia. Physiological Reports. 2021;9(10):e14876.
• 20. Zazzara MB, Bellieni A, Calvani R, Coelho-Junior HJ, Picca A, Marzetti E. Inflammaging at the Time of COVID-19. Clinics in Geriatric Medicine [Internet]. 2022 Mar [cited 2022 Jul 5]; Available from: http://dx.doi.org/10.1016/j.cger.2022.03.003
• 21. Müller L, Di Benedetto S. How Immunosenescence and Inflammaging May Contribute to Hyperinflammatory Syndrome in COVID-19. Int J Mol Sci. 2021 Nov 21;22(22):12539.
• 22. Fujioka T, Takahashi M, Mori M, Tsuchiya J, Yamaga E, Horii T, et al. Evaluation of the Usefulness of CO-RADS for Chest CT in Patients Suspected of Having COVID-19. Diagnostics (Basel). 2020 Aug 19;10(9):608.
• 23. Çomoğlu Ş, Öztürk S, Topçu A, Kulalı F, Kant A, Sobay R, et al. The Role of CO-RADS Scoring System in the Diagnosis of COVID-19 Infection and its Correlation with Clinical Signs. Current Medical Imaging. 18(4):381–6.
• 24. Akbar AN, Gilroy DW. Aging immunity may exacerbate COVID-19. Science. 2020 Jul 17;369(6501):256–7.
• 25. Ticinesi A, Lauretani F, Nouvenne A, Porro E, Fanelli G, Maggio M, et al. C-reactive protein (CRP) measurement in geriatric patients hospitalized for acute infection. Eur J Intern Med. 2017 Jan;37:7–12.