COVID-19 hastalarında telomer uzunluğunun analizi ve klinik-demografik verilerle ilişkisinin araştırılması

Year 2023, Volume: 48 Issue: 3, 833 - 843, 30.09.2023

Atakan Savrun , Ebubekir Dirican

https://doi.org/10.17826/cumj.1312436

Cited By: 1

Abstract

Amaç: Yeni koronavirüs hastalığı 2019 (COVID-19), Wuhan'daki 2019 salgınından önce bilinmeyen bulaşıcı bir hastalıktır. Bu çalışma, klinik-demografik parametrelerle COVID-19 (+) ve (-) numunelerinde telomer uzunluğunu değerlendirdi.
Gereç ve Yöntem: DNA COVID-19 (+) (n=70) ve (-) (n=70) hastalarından izole edildi. Telomer uzunluğu gerçek zamanlı PCR (RT-PCR) ile belirlendi. 2–∆∆Ct yöntemi, örneklerin telomer uzunluğunu analiz etmek için kullanıldı.
Bulgular: COVID-19 (+) hastalarında kreatinin, LDH, ferritin, WBC, NEU ve CRP'de COVID-19 (-) hastalara göre anlamlı fark vardı. NEU/LYM (veya N/L) oranı COVID-19 (+) hastalarında COVID-19 (-) hastalara göre daha yüksek bulundu. Öte yandan, COVID-19 (+) hastalarımızın telomer uzunluğu (ortalama ±standart sapma:0.93±0.58) COVID-19 (-) (ortalama ±standart sapma:1.26±0.76) olanlara göre anlamlı olarak daha kısaydı. Ayrıca COVID-19 (+) erkek hastaların telomer uzunluğu (ortalama±standart sapma:1.06±0.50) kadın hastalara (ortalama ±standart sapma:0.76±0.54) göre daha uzundu. Kan üre nitrojeni (BUN), yüksek kreatinin, yüksek hematokrit, yüksek NEU düzeyi, normal trombosit (PLT) ve düşük WBC düzeyi olan COVID-19 (+) hastalarda telomer uzunluğu anlamlı olarak daha kısaydı.
Sonuç: Bulgularımız, telomer uzunluğu ve kan parametre düzeylerinin COVID-19'un şiddetini etkilediğini göstermektedir. Kan parametrelerinin COVID-19 (+) ve COVID-19 (-) hastalarında farklılık gösterdiği tespit edildi. Sonuç olarak gelecekte benzer çalışmaların artması bulgularımızın önemini ortaya koyacaktır.

Keywords

COVID-19, telomer uzunluğu, RT-PCR

Analysis of telomere length in patients with COVID-19 and investigation into its relationship with clinical- demographic data

Abstract

Purpose: Novel coronavirus disease 2019 (COVID-19) is an infectious disease unknown before the 2019 outbreak in Wuhan. This study evaluated telomere length in COVID-19 (+) and (-) samples with clinical-demographic parameters.
Materials and Methods: DNA was isolated from COVID-19 (+) (n=70) and (-) (n=70) patients. Telomere length was determined by real-time-PCR (RT-PCR). The 2–∆∆Ct method was used to analyze the telomere length of the samples.
Results: There were significant differences in creatinine, LDH, ferritin, WBC, NEU and CRP in COVID-19 (+) patients compared to COVID-19 (-) patients. The NEU/LYM (or N/L) ratio was found higher in the patients with COVID-19 (+), than in COVID-19 (-). On the other hand, our COVID-19 (+) patients (mean±std:0.93±0.58) had significantly shorter telomere lengths than the COVID-19 (-) (mean±std:1.26±0.76). Moreover, COVID-19 (+) male patients (mean±std:1.06±0.50) had longer telomere length than female patients (mean±std:0.76±0.54). Telomere length was significantly shorter in patients with COVID-19 (+)with high blood urea nitrogen (BUN), high creatinine, high hematocrit, high NEU levels, normal platelets (PLT), and low WBC levels.
Conclusions: Our findings suggest that telomere length and blood parameter levels influence the severity of COVID-19. Blood parameters differed in patients with COVID-19 (+) and COVID-19 (-). As a result, increasing the number of similar studies in the future can demonstrate the significance of our findings.
Keywords: COVID-19, Telomere length, RT-PCR, NEU/LYM, blood

Keywords

COVID-19, Telomere length, RT-PCR, NEU/LYM, blood

References

• Sohrabi C, Alsafi Z, O’Neill N, Khan M, Kerwan A, Al-Jabir A et al. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19). Int J Surg. 2020;76:71-6.
• Mitra A, Ray Chaudhuri T, Mitra A, Pramanick P, Zaman S. Impact of COVID-19 related shutdown on atmospheric carbon dioxide level in the city of Kolkata. Parana J Sci Educ. 2020;6:84-92.
• Veer IMM, Riepenhausen A, Zerban M, Wackerhagen C, Puhlmann LMCMC, Engen H et al. Psycho-social factors associated with mental resilience in the Corona lockdown. Transl Psychiatry. 2021;11:67.
• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J et al. A Novel Coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-33.
• Touma M. COVID-19: molecular diagnostics overview. J Mol Med (Berl). 2020;98:947-54.
• Kempuraj D, Selvakumar GPP, Ahmed MEE, Raikwar SPP, Thangavel R, Khan A et al. COVID-19, mast cells, cytokine storm, psychological stress, and neuroinflammation. Neuroscientist. 2020;26:402-14.
• Debuc B, Smadja DM. Is COVID-19 a new hematologic disease? Stem Cell Rev Reports. 2021;17:4-8.
• Tjendra Y, Al Mana AF, Espejo AP, Akgun Y, Millan NC, Gomez-Fernandez C et al. Predicting disease severity and outcome in COVID-19 patients: a review of multiple biomarkers. Arch Pathol Lab Med. 2020;144:1465-74.
• Dirican E, Savrun ŞT, Aydın İE, Gülbay G, Karaman Ü. Analysis of mitochondrial DNA cytochrome‐b ( CYB ) and ATPase‐6 gene mutations in COVID‐19 patients. J Med Virol. 2022;94:3138-46.
• Connell NTT, Battinelli EMM, Connors JMM. Coagulopathy of COVID‐19 and antiphospholipid antibodies. J Thromb Haemost. 2020;18:E1-2.
• Bertolini A, Peppel IP, Bodewes FAJA, Moshage H, Fantin A, Farinati F, et al. Abnormal liver function tests in patients with COVID-19: relevance and potential pathogenesis. Hepatology. 2020;72:1864-72.
• López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153:1194-217.
• Broer L, Codd V, Nyholt DR, Deelen J, Mangino M, Willemsen G et al. Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect. Eur J Hum Genet. 2013;21:1163-8.
• Dugdale HL, Richardson DS. Heritability of telomere variation: it is all about the environment! Philos Trans R Soc Lond B Biol Sci. 2018;373:20160450.
• Effros RB, Pawelec G. Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion? Immunol. 1997;18:450-4.
• Olovnikov AM. A theory of marginotomy. J Theor Biol. 1973;41:181-90.
• Watson JD. Origin of Concatemeric T7DNA. Nat New Biol. 1972;239:197-201.
• Sanchez-Vazquez R, Guío-Carrión A, Zapatero-Gaviria A, Martínez P, Blasco MA. Shorter telomere lengths in patients with severe COVID-19 disease. Aging (Albany. NY). 2021;13:1-15.
• Froidure A, Mahieu M, Hoton D, Laterre P-F, Yombi JC, Koenig S, et al. Short telomeres increase the risk of severe COVID-19. Aging (Albany. NY). 2020;12:19911-22.
• Caslini C, Connelly JA, Serna A, Broccoli D, Hess JL. MLL Associates with telomeres and regulates telomeric repeat-containing RNA transcription. Mol Cell Biol. 2009;29:4519-26.
• Effros RB. Ageing and the immune system. Novartis Found Symp. 2001;235:130-9.
• Cohen S, Janicki-Deverts D, Turner RB, Casselbrant ML, Li-Korotky H-S, Epel ES, et al. Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults. JAMA. 2013;309:699.
• Sanchez-Vazquez R, Guío-Carrión A, Zapatero-Gaviria A, Martínez P, Blasco MA. Shorter telomere lengths in patients with severe COVID-19 disease. Aging (Albany. NY). 2021;13:1-15.
• Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, et al. Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank. EBioMedicine 2021;70:103485. doi: 10.1016/j.ebiom.2021.103485.
• Arantes, Pimenta R, Viana NI, Guimarães VR, Romão P, Candido P et al. Shorter leukocyte telomere length is associated with severity of COVID-19 infection. Biochem. Biophys. Reports. 2021;27:101056.
• Victor J, Deutsch J, Whitaker A, Lamkin EN, March A, Zhou P et al. SARS-CoV-2 triggers DNA damage response in Vero E6 cells. Biochem Biophys Res Commun. 2021;579:141-145.
• Kirkland JL, Tchkonia T. Cellular senescence: a translational perspective. EBioMedicine 2017;21:21-8.
• Gil ME, Coetzer TL. Real-time quantitative PCR of telomere length. Mol Biotechnol. 2004;27:169-72.
• Dirican E, Velidedeoğlu M, Ilvan S, Öztürk T, Altıntas T, Aynı EB et al. Identification of PIK3CA aberrations associated with telomere length in breast cancer. Gene Reports 2020;19:100597.
• Lin J, Smith DL, Esteves K, Drury S. Telomere length measurement by qPCR – Summary of critical factors and recommendations for assay design. Psychoneuroendocrinology. 2019;99:271-8.
• Zheng Lab. Telomere quantitative PCR Protocol. https://trn.tulane.edu/wp-content/uploads/sites/445/2021/08/Telomere-qPCR-protocol_August2021.pdf
• Liu S, Wang C, Green G, Zhuo H, Liu KD, Kangelaris KN et al. Peripheral blood leukocyte telomere length is associated with survival of sepsis patients. Eur Respir J. 2020;55:1901044.
• Tsilingiris D, Tentolouris A, Eleftheriadou I, Tentolouris N. Telomere length, epidemiology and pathogenesis of severe COVID‐19. Eur J Clin Invest. 2020;50:e13376.
• Aviv A, Shay JW. Reflections on telomere dynamics and ageing-related diseases in humans. Philos Trans R Soc B Biol Sci. 2018;373:20160436.
• Omran HM, Almaliki MS. Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis. J Infect Public Health. 2020;13:1196-201.
• Zhang NH, Cheng YC, Luo R, Zhang CX, Ge SW, Xu G. Recovery of new-onset kidney disease in COVID-19 patients discharged from hospital. BMC Infect Dis. 2021;21:397.
• Keski H. Hematological and inflammatory parameters to predict the prognosis in COVID-19. Indian J Hematol Blood Transfus. 2021;37:534-42.
• Banchini F, Cattaneo GM, Capelli P. Serum ferritin levels in inflammation: a retrospective comparative analysis between COVID-19 and emergency surgical non-COVID-19 patients. World J Emerg Surg. 2021;16:9.
• Fu L, Fei J, Xiang HX, Xiang Y, Tan ZX, Li MD et al. Analysis of death risk factors among 200 COVID-19 patients in Wuhan, China: A hospital-based case-cohort study. SSRN Electron J. 2020; PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3551430
• Demir HA. Changes in liver function in patients with COVID-19 and the demographics of the disease in a mid-sized city of Turkey: A retrospective analysis. Med Sci Discov. 2020;7:739-44.
• Guan W, Ni Z, Hu YYY, Liang W, Ou C, He J et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-20.
• Lei F, Liu YM, Zhou F, Qin JJ, Zhang P, Zhu L et al. Longitudinal association between markers of liver injury and mortality in COVID-19 in China. Hepatology. 2020;72:389-98.
• Elbistanli MS, Koçak HE, Acipayam H, Yiğider AP, Keskin M, Kayhan FT. The predictive value of neutrophil-lymphocyte and platelet-lymphocyte ratio for the effusion viscosity in otitis media with chronic effusion. J Craniofac Surg. 2017;28:e244-7.
• 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.
• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020;323:1061.
• Müezzinler A, Zaineddin AK, Brenner H. A systematic review of leukocyte telomere length and age in adults. Ageing Res Rev. 2013;12:509-19.
• Rebelo-Marques A, De Sousa Lages A, Andrade R, Ribeiro CF, Mota-Pinto A, Carrilho F et al. Aging hallmarks: The benefits of physical exercise. Front Endocrinol. (Lausanne). 2018;9:258.
• Bekaert S, De Meyer T, Rietzschel ER, De Buyzere ML, De Bacquer D, Langlois M et al. Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease. Aging Cell. 2007;6:639-47.
• Blackburn EH, Epel ES, Lin J. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science. 2015;350:1193-8.
• Iwama H, Ohyashiki K, Ohyashiki JH, Hayashi S, Yahata N, Ando K et al. Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals. Hum Genet. 1998;102:397-402.
• Armanios M, Blackburn EH. The telomere syndromes. Nat Rev Genet. 2012;13:693-704.
• Cronkhite JT, Xing C, Raghu G, Chin KM, Torres F, Rosenblatt RL et al. Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir Crit Care Med. 2008;178:729-37.
• Fernández-Real JM, Moreno-Navarrete JM, Ortega F, Ricart W. Decreased serum creatinine concentration is associated with short telomeres of adipose tissue cells. Obesity. 2011;19:1511-4.
• Suliman ME, Ansari MGA, Rayis MA, Hamza MA, Saeed AA, Mohammed AK et al. Telomere length and telomere repeat-binding protein in children with sickle cell disease. Pediatr. Res. 2022;91:539-44.
• Benetos A, Gardner JP, Kimura M, Labat C, Nzietchueng R, Dousset B, et al. Aldosterone and telomere length in white blood cells. Journals Gerontol. Ser. A Biol Sci Med Sci. 2005;60:1593-6.
• Colella MP, Santana BA, Conran N, Tomazini V, Costa FF, Calado RT, et al. Telomere length correlates with disease severity and inflammation in sickle cell disease. Rev Bras Hematol Hemoter. 2017;39:140-5.
• Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003;361:393-5.