Journal of Kerman University of Medical Sciences

Dexamethasone Treatment Considerably Reduces the Levels of Some Inflammatory Cytokines, Lactate Dehydrogenase, and C-Reactive Protein in COVID-19 Pneumonia Patients With Pre-existing COPD

Document Type : Original Article

Authors

Gholamreza Sepehri 1
Zeinab Fallah 2
Mitra Samareh Fekri 3
Behnam Dalfardi 4
Shahriar Dabiri 5
Hamid Daneshvar 6
Mohammad Javad Najafzadeh 7

1 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

2 Cardiovascular Research Center, Kerman University of Medical Sciences, Kerman, Iran

3 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

4 Department of Internal Medicine, Afzalipour Hospital, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

5 Department of Pathology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

6 Immunology Department, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

7 Department of Physiology- Pharmacology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

https://doi.org/10.34172/jkmu.2024.40
Abstract
Background: Dexamethasone is the most widely used corticosteroid for treating COVID-19 pulmonary complications. The effects of dexamethasone on serum inflammatory factors, including C-reactive protein (CRP), lactate dehydrogenase (LDH), and cortisol, were evaluated in COVID-19 pneumonia patients with pre-existing chronic obstructive pulmonary disease (COPD) in this study.
Methods: A total of 36 COVID-19 patients with pneumonia who had pre-existing COPD and were critically ill and 56 COVID-19- positive patients without pre-existing COPD were selected. A daily dose of 6–8 mg dexamethasone was administered during the hospitalization period. Some inflammatory markers (TNF-α, IL-10, and IL-6) and the serum levels of cortisol, LDH, and CRP were measured on admission and one week after hospitalization.
Results: TNF-α and IL-6 concentrations were significantly reduced and IL-10 significantly increased in all COVID-19 pneumonia patients with or without pre-existing COPD as a result of a daily dose of dexamethasone. Also, a significant reduction in cortisol, CRP, and LDH was observed following dexamethasone administration in all COVID-19 pneumonia patients, with or without preexisting COPD, with no correlation with gender, cigarette or waterpipe smoking, or opium abuse.
Conclusion: Our results showed a significant increase in TNF-α, IL-6, IL-10, cortisol, LDH, and CRP and a significant reduction in IL-10 in all critically ill COVID-19 pneumonia patients. Dexamethasone administration significantly reduced cortisol and proinflammatory cytokines and also LDH and CRP as the markers of COVID-19 severity.
 

Keywords

COVID-19
COPD
Dexamethasone
Inflammatory cytokines
Cortisol
C-reactive protein
Lactate dehydrogenase
Subjects
  1. Borges do Nascimento IJ, Cacic N, Abdulazeem HM, von Groote TC, Jayarajah U, Weerasekara I, et al. Novel coronavirus infection (COVID-19) in humans: a scoping review and meta-analysis. J Clin Med. 2020;9(4):941. doi: 10.3390/jcm9040941.
  2. Olwenyi OA, Dyavar SR, Acharya A, Podany AT, Fletcher CV, Ng CL, et al. Immuno-epidemiology and pathophysiology of coronavirus disease 2019 (COVID-19). J Mol Med (Berl). 2020;98(10):1369-83. doi: 10.1007/s00109-020-01961-4.
  3. Wu F, Zhou Y, Wang Z, Xie M, Shi Z, Tang Z, et al. Clinical characteristics of COVID-19 infection in chronic obstructive pulmonary disease: a multicenter, retrospective, observational study. J Thorac Dis. 2020;12(5):1811-23. doi: 10.21037/jtd- 20-1914.
  4. Gao Z, Xu Y, Sun C, Wang X, Guo Y, Qiu S, et al. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect. 2021;54(1):12-6. doi: 10.1016/j. jmii.2020.05.001.
  5. Castagnoli R, Votto M, Licari A, Brambilla I, Bruno R, Perlini S, et al. Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr. 2020;174(9):882-9. doi: 10.1001/ jamapediatrics.2020.1467.
  6. Rahman A, Niloofa R, Jayarajah U, De Mel S, Abeysuriya V, Seneviratne SL. Hematological abnormalities in COVID-19: a narrative review. Am J Trop Med Hyg. 2021;104(4):1188-201. doi: 10.4269/ajtmh.20-1536.
  7. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. doi: 10.1056/NEJMoa2002032.
  8. Wang X, Fang J, Zhu Y, Chen L, Ding F, Zhou R, et al. Clinical characteristics of non-critically ill patients with novel coronavirus infection (COVID-19) in a Fangcang hospital. Clin Microbiol Infect. 2020;26(8):1063-8. doi: 10.1016/j. cmi.2020.03.032.
  9. Tsai PH, Lai WY, Lin YY, Luo YH, Lin YT, Chen HK, et al. Clinical manifestation and disease progression in COVID-19 infection. J Chin Med Assoc. 2021;84(1):3-8. doi: 10.1097/ jcma.0000000000000463.
  10. Stasi C, Fallani S, Voller F, Silvestri C. Treatment for COVID-19: an overview. Eur J Pharmacol. 2020;889:173644. doi: 10.1016/j.ejphar.2020.173644.
  11. Wu YC, Chen CS, Chan YJ. The outbreak of COVID-19: an overview. J Chin Med Assoc. 2020;83(3):217-20. doi: 10.1097/jcma.0000000000000270.
  12. Liu T, Liang W, Zhong H, He J, Chen Z, He G, et al. Risk factors associated with COVID-19 infection: a retrospective cohort study based on contacts tracing. Emerg Microbes Infect. 2020;9(1):1546-53. doi: 10.1080/22221751.2020.1787799.
  13. Mousing CA, Sørensen D. Living with the risk of being infected: COPD patients’ experiences during the coronavirus pandemic. J Clin Nurs. 2021;30(11-12):1719-29. doi: 10.1111/jocn.15727.
  14. Xiao WW, Xu J, Shi L, Wang YD, Yang HY. Is chronic obstructive pulmonary disease an independent predictor for adverse outcomes in coronavirus disease 2019 patients? Eur Rev Med Pharmacol Sci. 2020;24(21):11421-7. doi: 10.26355/ eurrev_202011_23635.
  15. Lee SC, Son KJ, Han CH, Park SC, Jung JY. Impact of COPD on COVID-19 prognosis: a nationwide population-based study in South Korea. Sci Rep. 2021;11(1):3735. doi: 10.1038/s41598- 021-83226-9.
  16. Liao SY, Petrache I, Fingerlin TE, Maier LA. Association of inhaled and systemic corticosteroid use with coronavirus disease 2019 (COVID-19) test positivity in patients with chronic pulmonary diseases. Respir Med. 2021;176:106275. doi: 10.1016/j.rmed.2020.106275.
  17. Tan T, Khoo B, Mills EG, Phylactou M, Patel B, Eng PC, et al. Association between high serum total cortisol concentrations and mortality from COVID-19. Lancet Diabetes Endocrinol. 2020;8(8):659-60. doi: 10.1016/s2213-8587(20)30216-3.
  18. Pal R, Banerjee M, Bhadada SK. Cortisol concentrations and mortality from COVID-19. Lancet Diabetes Endocrinol. 2020;8(10):809. doi: 10.1016/s2213-8587(20)30304-1.
  19. Sun HB, Zhang YM, Huang LG, Lai QN, Mo Q, Ye XZ, et al. The changes of the peripheral CD4+lymphocytes and inflammatory cytokines in Patients with COVID-19. PLoS One. 2020;15(9):e0239532. doi: 10.1371/journal.pone.0239532.
  20. Rostamian A, Ghazanfari T, Arabkheradmand J, Edalatifard M, Ghaffarpour S, Salehi MR, et al. Interleukin-6 as a potential predictor of COVID-19 disease severity in hospitalized patients and its association with clinical laboratory routine tests. Immunoregulation. 2020;3(1):29-36. doi: 10.32598/ immunoregulation.3.1.4.
  1. Wu MY, Yao L, Wang Y, Zhu XY, Wang XF, Tang PJ, et al. Clinical evaluation of potential usefulness of serum lactate dehydrogenase (LDH) in 2019 novel coronavirus (COVID-19) pneumonia. Respir Res. 2020;21(1):171. doi: 10.1186/ s12931-020-01427-8.
  2. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-93. doi: 10.1001/jama.2020.12839.
  3. Ahuja S, Panigrahi BK, Dey N, Rajinikanth V, Gandhi TK. Deep transfer learning-based automated detection of COVID-19 from lung CT scan slices. Appl Intell (Dordr). 2021;51(1):571- 85. doi: 10.1007/s10489-020-01826-w.
  4. Luo X, Liu Y, Ren M, Zhang X, Janne E, Lv M, et al. Consistency of recommendations and methodological quality of guidelines for the diagnosis and treatment of COVID-19. J Evid Based Med. 2021;14(1):40-55. doi: 10.1111/jebm.12419.
  5. Alzghari SK, Acuña VS. Supportive treatment with tocilizumab for COVID-19: a systematic review. J Clin Virol. 2020;127:104380. doi: 10.1016/j.jcv.2020.104380.
  6. Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med. 2020;18(1):164. doi: 10.1186/s12967-020-02339-3.
  7. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384(8):693-704. doi: 10.1056/NEJMoa2021436.
  8. Lim MA, Pranata R. Worrying situation regarding the use of dexamethasone for COVID-19. Ther Adv Respir Dis. 2020;14:1753466620942131. doi: 10.1177/1753466620942131.
  9. Li N, Jie Z. The application of corticosteroids in COVID-19: a two-edged sword. J Transl Int Med. 2020;8(2):66-70. doi: 10.2478/jtim-2020-0011.
  10. Sun X, Wang T, Cai D, Hu Z, Chen J, Liao H, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev. 2020;53:38-42. doi: 10.1016/j. cytogfr.2020.04.002.
  11. Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine storm in COVID-19: the current evidence and treatment strategies. Front Immunol. 2020;11:1708. doi: 10.3389/fimmu.2020.01708.
  12. Buszko M, Park JH, Verthelyi D, Sen R, Young HA, Rosenberg AS. The dynamic changes in cytokine responses in COVID-19: a snapshot of the current state of knowledge. Nat Immunol. 2020;21(10):1146-51. doi: 10.1038/s41590-020-0779-1.
  13. Zeng Z, Yu H, Chen H, Qi W, Chen L, Chen G, et al. Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China. Crit Care. 2020;24(1):525. doi: 10.1186/s13054-020-03255-0.
  14. Rabbani G, Shariful Islam SM, Rahman MA, Amin N, Marzan B, Robin RC, et al. Pre-existing COPD is associated with an increased risk of mortality and severity in COVID-19: a rapid systematic review and meta-analysis. Expert Rev Respir Med. 2021;15(5):705-16. doi: 10.1080/17476348.2021.1866547.
  15. Zhao Q, Meng M, Kumar R, Wu Y, Huang J, Lian N, et al. The impact of COPD and smoking history on the severity of COVID-19: a systemic review and meta-analysis. J Med Virol. 2020;92(10):1915-21. doi: 10.1002/jmv.25889.
  16. Ge E, Li Y, Wu S, Candido E, Wei X. Association of pre-existing comorbidities with mortality and disease severity among 167,500 individuals with COVID-19 in Canada: a populationbased cohort study. PLoS One. 2021;16(10):e0258154. doi: 10.1371/journal.pone.0258154.
  17. Ssentongo P, Ssentongo AE, Heilbrunn ES, Ba DM, Chinchilli VM. Association of cardiovascular disease and 10 other preexisting comorbidities with COVID-19 mortality: a systematic review and meta-analysis. PLoS One. 2020;15(8):e0238215. doi: 10.1371/journal.pone.0238215.
  18. Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93(1):250-6. doi: 10.1002/jmv.26232.
  19. Ahmed MH, Hassan A. Dexamethasone for the treatment of coronavirus disease (COVID-19): a review. SN Compr Clin Med. 2020;2(12):2637-46. doi: 10.1007/s42399-020-00610-8.
  20. Chaudhuri D, Sasaki K, Karkar A, Sharif S, Lewis K, Mammen MJ, et al. Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis. Intensive Care Med. 2021;47(5):521-37. doi: 10.1007/s00134-021-06394-2.
  21. Mirsoleymani S, Nekooghadam SM, Ahmadi Marzaleh M, Peyravi M, Soltani A, Sharififar S, et al. Assessment of risk factors for severe coronavirus disease 2019 among Iranian patients. Iran Red Crescent Med J. 2020;22(2):e72. doi: 10.32592/ircmj.2020.22.9.72.
  22. Noreen S, Maqbool I, Madni A. Dexamethasone: therapeutic potential, risks, and future projection during COVID-19 pandemic. Eur J Pharmacol. 2021;894:173854. doi: 10.1016/j. ejphar.2021.173854.
  23. Świątkowska-Stodulska R, Berlińska A, Puchalska-Reglińska E. Cortisol as an independent predictor of unfavorable outcomes in hospitalized COVID-19 patients. Biomedicines. 2022;10(7):1527. doi: 10.3390/biomedicines10071527.
  24. Asif S, Frithiof R, Larsson A, Franzén S, Anderberg SB, Kristensen B, et al. Immuno-modulatory effects of dexamethasone in severe COVID-19-a Swedish cohort study. Biomedicines. 2023;11(1):164. doi: 10.3390/biomedicines11010164.
  25. Kino T, Burd I, Segars JH. Dexamethasone for severe COVID-19: how does it work at cellular and molecular levels? Int J Mol Sci. 2021;22(13):6764. doi: 10.3390/ijms22136764.
  26. Buckner SL, Loenneke JP, Loprinzi PD. Cross-sectional association between normal-range lactate dehydrogenase, physical activity and cardiovascular disease risk score. Sports Med. 2016;46(4):467-72. doi: 10.1007/s40279-015-0457-x.
  27. Zhang YQ, Dai HB, Wang JH, Li XY, Dai SM, Yao DD, et al. [Prognostic significance of serial determinations of lactate dehydrogenase in follow-up for patients with myelodysplastic syndrome]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2011;19(1):85-9. [Chinese].
  28. Ali AH, Mohamed SO, Elkhidir IH, Elbathani ME, Ibrahim AA, Elhassan AB, et al. The association of lymphocyte count, CRP, D-dimer, and LDH with severe coronavirus disease 2019 (COVID-19): a meta-analysis. Sudan J Med Sci. 2020;15(2):9- 23. doi: 10.18502/sjms.v15i5.7146.
  29. Choi YJ, Song JY, Hyun H, Nham E, Yoon JG, Seong H, et al. Prognostic factors of 30-day mortality in patients with COVID-19 pneumonia under standard remdesivir and dexamethasone treatment. Medicine (Baltimore). 2022;101(38):e30474. doi: 10.1097/md.0000000000030474.
  30. Hassan ME, Hasan HM, Sridharan K, Elkady A, ElSeirafi MM. Dexamethasone in severe COVID-19 infection: a case series. Respir Med Case Rep. 2020;31:101205. doi: 10.1016/j. rmcr.2020.101205.
  31. Kooistra EJ, van Berkel M, van Kempen NF, van Latum CRM, Bruse N, Frenzel T, et al. Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients. Crit Care. 2021;25(1):281. doi: 10.1186/ s13054-021-03717-z.
  32. Pinzón MA, Ortiz S, Holguín H, Betancur JF, Cardona Arango D, Laniado H, et al. Dexamethasone vs methylprednisolone high dose for COVID-19 pneumonia. PLoS One. 2021;16(5):e0252057. doi: 10.1371/journal.pone.0252057.
  33. Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30. doi: 10.1186/1710-1492-9-30.
  34. Poetker DM, Reh DD. A comprehensive review of the adverse effects of systemic corticosteroids. Otolaryngol Clin North Am. 2010;43(4):753-68. doi: 10.1016/j.otc.2010.04.003.
  35. Oray M, Abu Samra K, Ebrahimiadib N, Meese H, Foster CS. Long-term side effects of glucocorticoids. Expert Opin Drug Saf. 2016;15(4):457-65. doi: 10.1517/14740338.2016.1140743.
  36. Rice JB, White AG, Scarpati LM, Wan G, Nelson WW. Longterm systemic corticosteroid exposure: a systematic literature review. Clin Ther. 2017;39(11):2216-29. doi: 10.1016/j. clinthera.2017.09.011.
  37. Langarizadeh MA, Ranjbar Tavakoli M, Abiri A, Ghasempour A, Rezaei M, Ameri A. A review on function and side effects of systemic corticosteroids used in high-grade COVID-19 to prevent cytokine storms. EXCLI J. 2021;20:339-65. doi: 10.17179/excli2020-3196.
Journal of Kerman University of Medical Sciences
Volume 31, Issue 5
September and October 2024
Pages 259-265

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