Association of different biomarkers and CT value of RT-PCR with mortality in COVID-19 cases attended at tertiary care centre in India

Authors

  • Amresh Kumar Singh Assistant Professor and Head, Department of Microbiology, BRD Medical College, Gorakhpur, Uttar Pradesh. https://orcid.org/0000-0002-3179-7003
  • Sushil Kumar Assistant Professor, Department of Zoology, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur Uttar Pradesh-273001, India https://orcid.org/0000-0002-5552-2039
  • Suraj Prasad Research Scholar (PhD Student), Department of Zoology, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur Uttar Pradesh-273001, India
  • Indra P Adhikari Demonstrator, Department of Biochemistry, Baba Raghav Das Medical College, Gorakhpur, Uttar Pradesh-273013, India.
  • Vivek Gaur Junior Resident, Viral Research Diagnostic Laboratory, Department of Microbiology, Baba Raghav Das Medical College, Gorakhpur, UttarPradesh-273013, India https://orcid.org/0000-0002-7361-608X

Keywords:

SARS-CoV-2, RT-PCR, cycle thresholds (CT), biochemical markers, COVID-19, RdRp

Abstract

Background: Severe Acute Respiratory Syndrome- Corona Virus-2 (SARS-CoV-2) infection becomes the pandemic of coronavirus disease 2019 (COVID-19) shows drastic changes in health care system.

Aims and objectives: 1) To assess different biomarkers in COVID-19 cases, 2) To correlate biomarkers with cycle threshold (CT) value of Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and it’s role for prognosis of severe cases.

Material and Methods: Consecutive patients with positive for SARS-CoV-2 by RT-PCR with CT value less than 36 were included. A CT values were found for envelope (E-gene) as a screening gene and RNA dependent RNA polymerase (RdRp) as a confirmatory gene were amplified during RT-PCR. The severity of illness was assessed using different biochemical parameters for C-reactive protein (CRP), serum ferritin, D-dimer, lactate dehydrogenase (LDH), serum urea, and creatinine.

Results: We enrolled 395 SARS-CoV-2 positive symptomatic patients. Among these, 322 (81.5%) were recovered and remaining succumbed 73 (18.5%). The mean age and distribution of gender were similar among death vs. recovered patients. We found that death seen in more severe cases 56/91 (61.5%), while recovery was good in mild-moderate [287/304 (94.4%)]. CRP was significantly higher among death than recovered cases (p<0.05). D-dimer, serum ferritin and LDH were also elevated among death alone and also in severe cases except serum ferritin.

Conclusions: We concluded that, mortality occurs more in patients with lower CT values (or early peak) than recovered cases (p < 0.001). The elevated level of CRP, serum ferritin, D-dimer and LDH including lower value of CT are associated with higher mortality in severe cases of COVID-19.

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References

Perlman S. Another decade, another coronavirus. N Engl J Med 2020;382:760–62.

Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579(7798):265-69. https://www.nature.com/ articles/s41586-020-2008-3. Accessed 12 Feb 2021.

Singh AK, Pandey J, Adhikari IP, Gaur V, Kumar A, Prakash S, et al. Assessment of Severity and Outcome of COVID-19 Cases by Haematological and Biochemical Markers at Tertiary Care Centre in India. Journal of Advances in Medicine and Medical Research 2020;32(23):196-07.

Worldometers.info.(2021,January31) worldometer. Retrieved from https://www. worldometers.info/coronavirus/. Accessed 31 Jan 2021.

Tang D, Comish P, Kang R. The hallmarks of COVID-19 disease. PLoS Pathog 2020;16(5): e1008536.

Bennett J, Dolin R, Blaser MJ. Principles and Practice of Infectious Diseases. 8th Edition Elsevier/Saunders, PA, USA; 2014. https://www.elsevier.com/books/mandell-douglas-and-bennetts-principles-and-practice-of-infectious-diseases/bennett/978-1-4557-4801-3. Accessed 12 Feb 2021.

Erdogan O, Ok F, Carkci S, Durmus E. The Role of Urine Biochemical Parameters for Predicting Disease Severity In COVID-19 Patients. Authorea 2020. https://www.authorea.com/users/352283/ articles/481414-the-role-of-urine-biochemical-parameters-for-predicting-disease-severity-in-covid-19-patients. Accessed 15 Feb 2021.

Kermali M, Khalsa RK, Pillai K, Ismail Z, Harky A. The role of biomarkers in diagnosis of COVID-19-A systematic review. Life Sci 2020;254:117788.

Danwang C, Endomba FT, Nkeck JR, Wouna DLA, Robert A, Noubiap JJ. A meta-analysis of potential biomarkers associated with severity of coronavirus disease 2019 (COVID-19). Biomark Res 2020;8:37.

Caruso FP, Scala G, Cerulo L, Ceccarelli M. A review of COVID-19 biomarkers and drug targets: resources and tools. Brief Bioinform 2021;22(2):701-13.

Marnell L, Mold C, Du Clos TW. C-reactive protein: ligands, receptors and role in inflammation. Clin Immunol 2005;117(2):104-11.

Wang G, Wu C, Zhang Q, Wu F, Yu B, Lv J. C-Reactive Protein Level May Predict the Risk of COVID-19 Aggravation. Open Forum Infect Dis 2020;7(5):ofaa153.

Harper PL, Theakston E, Ahmed J, Ockelford P. D-dimer concentration increases with age reducing the clinical value of the D-dimer assay in the elderly. Intern Med J 2007; 37: 607-13.

Yao Y, Cao J, Wang Q, Shi Q, Liu K, Luo Z. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study. J Intensive Care 2020;8:49. https://jintensivecare.biomedcentral.com/articles/10.1186/s40560-020-00466-z. Accessed 20 Feb 2021.

Luo M, Guo L, Yu M, Jiang W, Wang H. The psychological and mental impact of coronavirus disease 2019 (COVID-19) on medical staff and general public - A systematic review and meta-analysis. Psychiatry Res 2020;291:113190.

Malik P, Patel U, Mehta D, Patel N, Kelkar R, Akrmah. Biomarkers and outcomes of COVID-19 hospitalizations: systematic review and meta-analysis. BMJ Evid Based Med 2020;bmjebm-2020-111536.https://ebm.bmj.com/content/early/2020/09/14/bmjebm-2020-111536. Accessed 20 Feb 2021.

Keddie S, Ziff O, Chou MKL, Taylor RL, Heslegrave A, Garr E. Laboratory biomarkers associated with COVID-19 severity and management. Clinical Immunology 2020;221:108614.

Dobler CC. Biomarkers in respiratory diseases. Breathe (Sheff). 2019;15(4):265-66.

Tom MR, Mina MJ. To Interpret the SARS-CoV-2 Test, Consider the Cycle Threshold Value. Clin Infect Dis 2020;71(16):2252-254.

Joynt GM, Wu WK. Understanding COVID-19: what does viral RNA load really mean?Lancet Infect Dis 2020;20(6):635-36.

Guidance on Personal Protective Equipment (PPE) To Be Used By Healthcare Workers during Management of Patients with Confirmed Ebola or Persons under Investigation (PUIs) for Ebola who are Clinically Unstable or Have Bleeding, Vomiting, or Diarrhea in U.S. Hospitals, Including Procedures for Donning and Doffing PPE. Centre for Disease Control and Prevention, Atlanta USA.https://www.cdc.gov/vhf/ebola/healthcare-us/ppe/guidance.html. Accessed 22 Feb 2021.

Fan G, Tu C, Zhou F, Liu Z, Wng Y, Song B. Comparison of severity scores for COVID-19 patients with pneumonia: a retrospective study. Eur Respir J 2020;56(3):2002113.

Karahasan Yagci A, Sarinoglu RC, Bilgin H, Yanilmaz O,Sayin E, Deniz G. Relationship of the cycle threshold values of SARS-CoV-2 polymerase chain reaction and total severity score of computerized tomography in patients with COVID 19. Int J Infect Dis 2020;101:160-66.

Perrotta F, Corbi G, Mazzeo G, Boccia M, Aronne L, D’Agnano V. COVID-19 and the elderly: insights into pathogenesis and clinical decision-making. Aging Clin Exp Res 2020;32(8):1599-608.

Nikolich-Zugich J, Knox KS, Rios CTNatt B, Bhattacharya D, Fain MJ. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. Gero Science 2020; 42(2):505–14.

Cortis D. On Determining the Age Distribution of COVID-19 Pandemic. Front Public Health 2020;8:202.

Downing G. Biomarkers definitions working group Biomarkers and surrogate endpoints. Clin Pharmacol Ther 2001;69:89–95.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet 2020;395(10223):507.

Young B, Gleeson M, Cripps AW. C-reactive protein: a critical review. Pathology 1991;23(2):118-24.

Gao Y, Li T, Han M, Li X, Wu D, Xu Y. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol 2020;10.

Linkins LA, Takach Lapner S. Review of D-dimer testing: good, bad, and ugly. Int J Lab Hematol 2017;39(S1):98–103.

Querol-Ribelles JM, Tenias JM, Grau E. Plasma d-dimer levels correlate with outcomes in patients with community-acquired pneumonia. Chest 2004;126(4):1087–92.

Yu HH, Qin C, Chen M, Wang W, Tian DS. D-dimer level is associated with the severity of COVID-19. Thromb Res 2020;195:219-25.

Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell 2008;134(5):703–07.

Kolev Y, Uetake H, Takagi Y, Sugihara K. Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis. Ann Surg Oncol 2008;15(8):2336–44.

Uchide N, Ohyama K, Bessho T, Toyoda H. Lactate dehydrogenase leakage as a marker for apoptotic cell degradation induced by influenza virus infection in human fetal membrane cells. Intervirology 2009;52(3):164–73.

Annweiler C, Sacco G, Salles N, Aquino JP, Gautier J, Berrut G. National French Survey of Coronavirus Disease (COVID-19) Symptoms in People Aged 70 and Over. Clin Infect Dis 2021;72(3):490-94.

Huang JT, Ran RX, Lv ZH, Freng LN, Ran CY, Tong YQ. Chronological Changes of Viral Shedding in Adult In patients With COVID-19 in Wuhan, China. Clin Infect Dis 2020;71(16):2158-66.

Velavan TP, Meyer CG. Mild versus severe COVID-19:Laboratory markers. Int J Infec Dis. 2020;95:304-07.

Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;71:762-68.

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Published

2021-06-30

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Original Research Articles

How to Cite

Association of different biomarkers and CT value of RT-PCR with mortality in COVID-19 cases attended at tertiary care centre in India. (2021). International Journal of Biomedical and Advance Research, 12(6), e5610. https://ssjournals.co.in/index.php/ijbar/article/view/5610