Klinik Araştırma
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Covid-19 hastalarında Hypoxia-Inducible Factor 1α hastalık şiddeti ve prognozunu belirlemede bir biyomarker olabilir mi?

Yıl 2021, Cilt 11, Sayı 4, 462 - 468, 31.07.2021

Öz

Bu çalışmada akut akciğer hasarı durumlarında bir çok dokuda ve pulmoner dokuda düzeyleri 100 kat artan HIF-1a’nın serum düzeylerinin Covid-19 hastalarında hastalığın şiddeti ve prognozunu takipte etkili bir parametre olarak kullanılıp kullanılamayacağı sorularına yanıt aramak amaçlanmıştır. Çalışmaya Covid-19 klinik şikayetleri ile başvuran 40 hasta ve 20 sağlıklı kontrol bireyi dahil edildi. Hasta grubundan 20 hastanın PCR testi ile Covid-19 tanısı doğrulandı. Diğer 20 hasta ise Covid-19 şüpheli grup olarak kabul edildi. Hasta gruplarının başvuru klinik ve laboratuvar verileri kaydedildi. Covid-19 grubu hastaların başvuru günü ve başvuru sonrası 1. Hafta kan örneklerinden laboratuvar testleri ve serum HIF-1α düzeyleri ölçüldü. Covig-19 grubu hastalık şiddetine göre dört alt gruba ayrılıp her grubun HIF-1α değerleri birbirleri ile karşılaştırıldı. Bu çalışmada covid-19 doğrulanmış hasta grubunda serum HIF-1α değerlerinin sağlıklı kontrol grup serum HIF-1α değerlerinden daha yüksek olduğu bulundu. Bununla birlikte Covid-19 şüpheli grup ile arasında anlamlı farklılık bulunamadı. Covid-19 doğrulanmış hasta grubunda hastane yatış günü serum HIF-1α değerlerinin yatış sonrası HIF-1α değerlerinden yüksek bulunurken, monosit, platelet ve ferritin değerleri ise düşüktü. Covid-19 doğrulanmış hasta grubunun kritik alt grubunun 1. hafta serum HİF-1α değerleri hafif alt grup 0. Gün ve 1. Hafta değerlerinden anlamlı düzeyde düşüktü. Covid-19 grup HIF-1α değerleri hasta yaşı ile güçlü negatif korele bulunurken, platelet sayıları ile zayıf pozitif körele bulundu. COVİD-19 hastalarında alveolar hasarı engellediği düşünülen HIF-1α düzeyleri yükselmektedir. Bununla birlikte HIF-1α düşük seyreden COVİD-19 hastalarında yeterli artış olmaması klinik tablonun ağırlaşmasından sorumlu bir faktör olarak da göz önünde bulundurulabilir.

Kaynakça

  • [1] The 2019-nCoV Outbreak Joint Field Epidemiology Investigation Team, Li Q. Notes from the field: an outbreak of NCIP (2019-nCoV) infection in China — Wuhan, Hubei Province, 2019–2020. China CDC Weekly 2020;2:79-80.
  • [2] Tan WJ, Zhao X, Ma XJ, et al. A novel coronavirus genome identified in a cluster of pneumonia cases — Wuhan, China 2019–2020. China CDC Weekly 2020;2:61-62.
  • [3] Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-733.
  • [4] WHO. Novel Coronavirus (2019-nCoV) Situation Report—22. https://www.who.int/docs/defaultsource/coronaviruse/situation-reports/20200211sitrep-22-ncov.pdf?sfvrsn=fb6d49b1_2. Accessed 12 Feb 2020.
  • [5] Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–574.
  • [6] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in wuhan, china [J]. Lancet. 2020;395:497-506.
  • [7] Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. [8] Meng H, Xiong R, He R, et al. CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China. J Infect. 2020;81(1):33-39.
  • [9] Gabutti G, d'Anchera E, Sandri F, Savio M, Stefanati A. Coronavirus: Update Related to the Current Outbreak of COVID-19. Infect Dis Ther. 2020;9(2):1-13.
  • [10] Gorbalenya A.E., Baker S.C., Baric R.S. et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses-a statement of the Coronavirus Study Group. bioRxiv. 2020 02.07.937862.
  • [11] Adams JM, Difazio LT, Rolandelli RH, et al. HIF-1: a key mediator in hypoxia. Acta Physiol Hung. 2009;96(1):19-28.
  • [12] Bogdanovski DA, DiFazio LT, Bogdanovski AK, et al. Hypoxia-inducible-factor-1 in trauma and critical care. J Crit Care. 2017;42:207-212.
  • [13] Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1995;151(2):293-301.
  • [14] Sevransky JE, Levy MM, Marini JJ. Mechanical ventilation in sepsis-induced acute lung injury/acute respiratory distress syndrome: an evidence-based review. Crit Care Med. 2004;32(11):548-553.
  • [15] Sherman MA, Suresh MV, Dolgachev VA, et al. Molecular Characterization of Hypoxic Alveolar Epithelial Cells After Lung Contusion Indicates an Important Role for HIF-1α. Ann Surg. 2018;267(2):382-391.
  • [16] McClendon J, Jansing NL, Redente EF, et al. Hypoxia-Inducible Factor 1α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury. Am J Pathol. 2017;187(8):1772-1786.
  • [17] Matsuishi Y, Jesmin S, Kawano S, et al. Landiolol hydrochloride ameliorates acute lung injury in a rat model of early sepsis through the suppression of elevated levels of pulmonary endothelin-1. Life Sci. 2016;166:27-33.
  • [18] Peiris JS, Chu CM, Cheng VC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767-1772.
  • [19] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China [published correction appears in Lancet. 2020 Jan 30;:]. Lancet. 2020;395(10223):497-506.
  • [20] Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513.
  • [21] Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-1207.
  • [22] Song F, Shi N, Shan F, et al. Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology. 2020;295(1):210-217.
  • [23] Chen L, Liu HG, Liu W, et al. Zhonghua Jie He He Hu Xi Za Zhi. 2020;43(0):E005.
  • [24] Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19). J Gen Intern Med. 2020;35(5):1545-1549.
  • [25] Zhang H, Shang W, Liu Q, Zhang X, Zheng M, Yue M. Clinical characteristics of 194 cases of COVID-19 in Huanggang and Taian, China. Infection. 2020;1-8.
  • [26] 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):1021-1028.
  • [27] Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353(16):1685-1693.
  • [28] Wheeler AP, Bernard GR. Acute lung injury and the acute respiratory distress syndrome: a clinical review. Lancet. 2007;369(9572):1553-1564.
  • [29] Thelin EP, Nelson DW, Bellander BM. Secondary peaks of S100B in serum relate to subsequent radiological pathology in traumatic brain injury. Neurocrit Care. 2014;20(2):217-229.
  • [30] Undén L, Calcagnile O, Undén J, Reinstrup P, Bazarian J. Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults. BMC Med. 2015;13:292.

Can Hypoxia-Inducible Factor 1α be used as a biomarker to evaluate disease severity and prognosis in COVID-19 patients?

Yıl 2021, Cilt 11, Sayı 4, 462 - 468, 31.07.2021

Öz

This study was aimed to answer the questions of whether the serum levels of Hypoxia-Inducible Factor 1α (HIF-1α), which is increased by up to 100 times in many tissues including pulmonary tissue in cases of acute lung injury, could be used as a parameter for monitoring the severity and prognosis in COVID-19 patients. Fourty patients, who were admitted to the hospital with COVID-19 clinical symptoms, and 20 healthy control subjects were included in the study. The diagnosis of 20 patients within the patient group were confirmed by the PCR test. The remaining 20 patients were regarded as COVID-19 suspect group. Clinical and laboratory data of patients on admission were recorded. Clinical laboratory tests and serum HIF-1α levels were measured from the blood samples of COVID-19 group on the day of admission and one week after hospitalization. COVID-19 group was divided into four subgroups according to disease severity and HIF-1α values of each group were compared.In this study, serum HIF-1α values of confirmed COVID-19 patient group were measured higher than healthy control group’s serum HIF-1α values, however no significant difference was found for the COVID-19 suspect group. Within confirmed COVID-19 group, serum HIF-1α values on admission were higher than values after hospitalization, whereas Monocyte count, Platelet count and Ferritin values were lower. Among the confirmed COVID-19 cases, critically ill subgroup’s serum HIF-1α levels of the first week were significantly lower than mild subgroup’s serum HIF-1α levels of both the first week and the day of admission. HIF-1α values of COVID-19 group were strongly negative correlated with age, whereas weakly positive correlated with platelet counts. HIF-1α, which are thought to prevent alveolar damage, increased in COVID-19 patients. Additionally, low levels of HIF-1α in COVID-19 patients might be considered as a factor responsible for the aggravation of the clinical severity.

Kaynakça

  • [1] The 2019-nCoV Outbreak Joint Field Epidemiology Investigation Team, Li Q. Notes from the field: an outbreak of NCIP (2019-nCoV) infection in China — Wuhan, Hubei Province, 2019–2020. China CDC Weekly 2020;2:79-80.
  • [2] Tan WJ, Zhao X, Ma XJ, et al. A novel coronavirus genome identified in a cluster of pneumonia cases — Wuhan, China 2019–2020. China CDC Weekly 2020;2:61-62.
  • [3] Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-733.
  • [4] WHO. Novel Coronavirus (2019-nCoV) Situation Report—22. https://www.who.int/docs/defaultsource/coronaviruse/situation-reports/20200211sitrep-22-ncov.pdf?sfvrsn=fb6d49b1_2. Accessed 12 Feb 2020.
  • [5] Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–574.
  • [6] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in wuhan, china [J]. Lancet. 2020;395:497-506.
  • [7] Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. [8] Meng H, Xiong R, He R, et al. CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China. J Infect. 2020;81(1):33-39.
  • [9] Gabutti G, d'Anchera E, Sandri F, Savio M, Stefanati A. Coronavirus: Update Related to the Current Outbreak of COVID-19. Infect Dis Ther. 2020;9(2):1-13.
  • [10] Gorbalenya A.E., Baker S.C., Baric R.S. et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses-a statement of the Coronavirus Study Group. bioRxiv. 2020 02.07.937862.
  • [11] Adams JM, Difazio LT, Rolandelli RH, et al. HIF-1: a key mediator in hypoxia. Acta Physiol Hung. 2009;96(1):19-28.
  • [12] Bogdanovski DA, DiFazio LT, Bogdanovski AK, et al. Hypoxia-inducible-factor-1 in trauma and critical care. J Crit Care. 2017;42:207-212.
  • [13] Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1995;151(2):293-301.
  • [14] Sevransky JE, Levy MM, Marini JJ. Mechanical ventilation in sepsis-induced acute lung injury/acute respiratory distress syndrome: an evidence-based review. Crit Care Med. 2004;32(11):548-553.
  • [15] Sherman MA, Suresh MV, Dolgachev VA, et al. Molecular Characterization of Hypoxic Alveolar Epithelial Cells After Lung Contusion Indicates an Important Role for HIF-1α. Ann Surg. 2018;267(2):382-391.
  • [16] McClendon J, Jansing NL, Redente EF, et al. Hypoxia-Inducible Factor 1α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury. Am J Pathol. 2017;187(8):1772-1786.
  • [17] Matsuishi Y, Jesmin S, Kawano S, et al. Landiolol hydrochloride ameliorates acute lung injury in a rat model of early sepsis through the suppression of elevated levels of pulmonary endothelin-1. Life Sci. 2016;166:27-33.
  • [18] Peiris JS, Chu CM, Cheng VC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767-1772.
  • [19] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China [published correction appears in Lancet. 2020 Jan 30;:]. Lancet. 2020;395(10223):497-506.
  • [20] Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513.
  • [21] Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-1207.
  • [22] Song F, Shi N, Shan F, et al. Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology. 2020;295(1):210-217.
  • [23] Chen L, Liu HG, Liu W, et al. Zhonghua Jie He He Hu Xi Za Zhi. 2020;43(0):E005.
  • [24] Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19). J Gen Intern Med. 2020;35(5):1545-1549.
  • [25] Zhang H, Shang W, Liu Q, Zhang X, Zheng M, Yue M. Clinical characteristics of 194 cases of COVID-19 in Huanggang and Taian, China. Infection. 2020;1-8.
  • [26] 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):1021-1028.
  • [27] Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353(16):1685-1693.
  • [28] Wheeler AP, Bernard GR. Acute lung injury and the acute respiratory distress syndrome: a clinical review. Lancet. 2007;369(9572):1553-1564.
  • [29] Thelin EP, Nelson DW, Bellander BM. Secondary peaks of S100B in serum relate to subsequent radiological pathology in traumatic brain injury. Neurocrit Care. 2014;20(2):217-229.
  • [30] Undén L, Calcagnile O, Undén J, Reinstrup P, Bazarian J. Validation of the Scandinavian guidelines for initial management of minimal, mild and moderate traumatic brain injury in adults. BMC Med. 2015;13:292.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Orjinal Araştırma
Yazarlar

Köksal DEVECİ (Sorumlu Yazar)
Tokat Gaziosmanpaşa Üniversitesi, Tıp Fakültesi, Tıbbi Biyokimya Anabilimdalı
0000-0003-1531-8567
Türkiye


Zeliha Cansel ÖZMEN
TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ
0000-0001-9045-2518
Türkiye


Umut ŞAY COŞKUN
TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ
0000-0002-4359-4799
Türkiye


Samet ÇAM Bu kişi benim
TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ
0000-0003-0604-0962
Türkiye

Yayımlanma Tarihi 31 Temmuz 2021
Kabul Tarihi 2 Nisan 2021
Yayınlandığı Sayı Yıl 2021, Cilt 11, Sayı 4

Kaynak Göster

AMA Deveci K. , Özmen Z. C. , Şay Coşkun U. , Çam S. Can Hypoxia-Inducible Factor 1α be used as a biomarker to evaluate disease severity and prognosis in COVID-19 patients?. J Contemp Med. 2021; 11(4): 462-468.