EFFECT OF PULSE STEROID THERAPY ON MORTALITY IN SEVERE COVID-19 PNEUMONIA

Year 2021, Volume: 28 Issue: 3, 479 - 486, 13.09.2021

Ahmet Bindal

https://doi.org/10.17343/sdutfd.982218

Abstract

Objective
We aimed to observe the effect of pulse steroid
therapy used in the hyperinflammatory phase that
occurs during the course of the COVID-19 disease
on the inflammatory markers and clinical conditions
of the patients.
Materials and Methods
In this study, 30 patients with positive COVID-19 PCR
(polymerase chain reaction) test who were treated
with pulse steroid (high-dose methylprednisolone)
due to the hyperinflammatory phase were evaluated.
The clinical conditions and inflammatory markers
of the patients were retrospectively analyzed.
Patients were evaluated in terms of age, gender,
intubation status, clinical improvement, discharge,
mortality rate, 24th, 48th, 72nd hours and 7th days
after treatment initiation, C-reactive protein (CRP),
procalcitonin, ferritin, oxygen saturation values,
lymphocyte count.
Results
A total of 30 patients; 21 male and 9 female, who
received pulse steroid therapy were examined. The
median age was calculated as 66 [31-88]. In the
study, 15 (50%) patients died, of which 11 were male
and 4 were female. When the survived and deceased
patients were compared, it was observed that the
values of ferritin, CRP procalcitonin measured at
72 hours and 7 days after pulse steroid treatment
decreased significantly in the survived patient group.
(72nd hour p-values=0.01-0.08- <0.05, respectively)
(7th day p-value=0.01-0.07-<0.05, respectively)
Conclusion
The significant decrease in inflammatory markers
such as ferritin and CRP after pulse steroid therapy
and the fact that this decrease is more obvious in the
survived patient group suggests that steroids can be
used in hyperinflammatory processes.

Keywords

COVID-19, pulse steroid therapy, CRP, ferritin

AĞIR COVID-19 PNÖMONİSİNDE PULSE STEROİD TEDAVİSİNİN MORTALİTE ÜZERİNE ETKİSİ

Abstract

COVID-19 hastalığının süreci esnasında ortaya çıkan
hiperinflamatuar fazda kullanılan pulse steroid tedavisinin
hastaların inflamatuar belirteçlerine ve klinik
durumlarına etkisini gözlemlemeyi amaçladık.
Gereç ve Yöntem
Bu çalışmada hiperinflamatuar faz nedeniyle pulse
steroid (yüksek doz metilprednizolon) ile tedavi edilen,
COVID-19 PCR (polimeraz zincir reaksiyonu)
testi pozitif olan 30 hasta değerlendirildi. Hastaların
klinik durumları ve inflamatuar belirteçleri retrospektif
olarak incelendi. Hastalar; yaş, cinsiyet, entübasyon
durumu, klinik düzelme, taburculuk, mortalite oranı,
tedavi başlangıcından 24-48-72. saat ve 7. günde ölçülen;
C-reaktif protein (CRP), prokalsitonin, ferritin,
oksijen saturasyon değeri ve lenfosit sayısı açısından
değerlendirildi.
Bulgular
Toplamda pulse steroid tedavisi alan 21 erkek, 9 kadın
olmak üzere 30 hasta incelendi. Ortanca yaş 66
[31-88] olarak hesaplandı. Çalışmada 15 (%50) hasta
vefat etmiş olup, bunun 11’i erkek, 4’ü kadın hastaydı.
Yaşayan ve ölen hastalar karşılaştırıldıklarında; pulse
steroid tedavisi sonrası 72. saat ve 7. günde ölçülen
ferritin, CRP, prokalsitonin değerlerinin yaşayan hasta
grubunda anlamlı olarak azaldığı görüldü. (sırasıyla
72. saat p= 0,01; 0,08 ; <0,05) (sırasıyla 7. gün p =
0,01; 0,07 ; <0,05)
Sonuç
Pulse steroid tedavisi sonrası ferritin, CRP gibi inflamatuar
belirteçlerin anlamlı olarak azalması ve bu
azalmanın yaşayan hasta grubunda daha belirgin olması,
steroidlerin hiperinflamatuar süreçlerde kullanılabileceğini
düşündürmektedir.

Keywords

COVİD-19, pulse steroid tedavisi, CRP, ferritin

References

• 1. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi. 2020;41(2):145-51. PubMed PMID: 32064853. Epub 2020/02/18.
• 2. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England). 2020;395(10223):497- 506. PubMed PMID: 31986264. Pubmed Central PMCID: PMC7159299. Epub 2020/01/28. eng.
• 3. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. COVID-19 in Critically Ill Patients in the Seattle Region - Case Series. The New England journal of medicine. 2020;382(21):2012-22. PubMed PMID: 32227758. Pubmed Central PMCID: PMC7143164. Epub 2020/04/01. eng.
• 4. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2020;39(5):405-7. PubMed PMID: 32362390. Pubmed Central PMCID: PMC7118652. Epub 2020/05/05. eng.
• 5. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet (London, England). 2020;395(10229):1033-4. PubMed PMID: 32192578. Pubmed Central PMCID: PMC7270045. Epub 2020/03/21. eng.
• 6. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020;395(10223):473-5. PubMed PMID: 32043983. Pubmed Central PMCID: PMC7134694. Epub 2020/02/12. eng.
• 7. 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(11):1061-9. PubMed PMID: 32031570. Pubmed Central PMCID: PMC7042881. Epub 2020/02/08. eng.
• 8. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical immunology. 2020;214:108393. PubMed PMID: 32222466. Pubmed Central PMCID: PMC7102614. Epub 2020/03/31. eng.
• 9. Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN. Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs. 2020;80(13):1267-92. PubMed PMID: 32696108. Pubmed Central PMCID: PMC7372203 Epub 2020/07/23. eng.
• 10. Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(20):10970-5. PubMed PMID: 32350134. Pubmed Central PMCID: PMC7245089. Epub 2020/05/01. eng.
• 11. Myall KJ, Mukherjee B, Castanheira AM, Lam JL, Benedetti G, Mak SM, et al. Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment. Annals of the American Thoracic Society. 2021;5(5):799- 806. PubMed PMID: 33433263. Pubmed Central PMCID: PMC8086530. Epub 2021/01/13. eng.
• 12. Edalatifard M, Akhtari M, Salehi M, Naderi Z, Jamshidi A, Mostafaei S, et al. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. The European respiratory journal. 2020;56(6). PubMed PMID: 32943404. Pubmed Central PMCID: PMC7758541 Epub 2020/09/19. eng.
• 13. Aricò M, Danesino C, Pende D, Moretta L. Pathogenesis of haemophagocytic lymphohistiocytosis. British journal of haematology. 2001;114(4):761-9. PubMed PMID: 11564062. Epub 2001/09/21. eng.
• 14. Wang H, Ma S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. The American journal of emergency medicine. 2008;26(6):711-5. PubMed PMID: 18606328. Epub 2008/07/09. eng.
• 15. Awasthi S, Wagner T, Venkatakrishnan AJ, Puranik A, Hurchik M, Agarwal V, et al. Plasma IL-6 levels following corticosteroid therapy as an indicator of ICU length of stay in critically ill COVID-19 patients. Cell death discovery. 2021;7(1):55. Pub- Med PMID: 33723251. Pubmed Central PMCID: PMC7958587 Epub 2021/03/17. eng.
• 16. Zielińska KA, Van Moortel L, Opdenakker G, De Bosscher K, Van den Steen PE. Endothelial Response to Glucocorticoids in Inflammatory Diseases. Frontiers in immunology. 2016;7:592. PubMed PMID: 28018358. Pubmed Central PMCID: PMC5155119. Epub 2016/12/27. eng.
• 17. Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. The Lancet Respiratory medicine. 2020;8(3):267-76. PubMed PMID: 32043986. Epub 2020/02/12. eng.
• 18. Zhang G, Wang J, Yao G, Shi B. Efficacy of high-dose methylprednisolone pulse therapy in the treatment of enterovirus 71 encephalitis. Pakistan journal of pharmaceutical sciences. 2016;29(4 Suppl):1421-7. PubMed PMID: 27592493. Epub 2016/09/07. eng.
• 19. Fujinaga S, Sakuraya K. Inhibitory effect of steroid on absorption fever after percutaneous renal biopsy. Pediatrics international : official journal of the Japan Pediatric Society. 2019;61(5):512-3. PubMed PMID: 31099057. Epub 2019/05/18. eng.
• 20. Vatti RR, Ali F, Teuber S, Chang C, Gershwin ME. Hypersensitivity reactions to corticosteroids. Clinical reviews in allergy & immunology. 2014;47(1):26-37. PubMed PMID: 23567983. Epub 2013/04/10. eng.
• 21. Ko FW, Chan KP, Hui DS, Goddard JR, Shaw JG, Reid DW, et al. Acute exacerbation of COPD. Respirology (Carlton, Vic). 2016;1(7):1152-65. PubMed PMID: 27028990. Pubmed Central PMCID: PMC7169165. Epub 2016/03/31. eng.
• 22. Fernández-Cruz A, Ruiz-Antorán B, Muñoz-Gómez A, Sancho- López A, Mills-Sánchez P, Centeno-Soto GA, et al. A Retrospective Controlled Cohort Study of the Impact of Glucocorticoid Treatment in SARS-CoV-2 Infection Mortality. Antimicrobial agents and chemotherapy. 2020;64(9). PubMed PMID: 32571831. Pubmed Central PMCID: PMC7449182. Epub 2020/06/24. eng.
• 23. Selvaraj V, Dapaah-Afriyie K, Finn A, Flanigan TP. Short-Term Dexamethasone in Sars-CoV-2 Patients. Rhode Island medical journal (2013). 2020;103(6):39-43. PubMed PMID: 32570995. Epub 2020/06/24. eng.
• 24. Stockman LJ, Bellamy R, Garner P. SARS: systematic review of treatment effects. PLoS medicine. 2006;3(9):e343. PubMed PMID: 16968120. Pubmed Central PMCID: PMC1564166. Epub 2006/09/14. eng.
• 25. Sung JJ, Wu A, Joynt GM, Yuen KY, Lee N, Chan PK, et al. Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak. Thorax. 2004;59(5):414-20. Pub- Med PMID: 15115870. Pubmed Central PMCID: PMC1746995. Epub 2004/04/30. eng.
• 26. Hui DS. Systemic Corticosteroid Therapy May Delay Viral Clearance in Patients with Middle East Respiratory Syndrome Coronavirus Infection. American journal of respiratory and critical care medicine. 2018;197(6):700-1. PubMed PMID: 29227752. Epub 2017/12/12. eng.
• 27. Wang J, Yang W, Chen P, Guo J, Liu R, Wen P, et al. The proportion and effect of corticosteroid therapy in patients with COVID-19 infection: A systematic review and meta-analysis. PloS one. 2021;16(4):e0249481. PubMed PMID: 33882090. Pubmed Central PMCID: PMC8059814. Epub 2021/04/22. eng.
• 28. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in Hospitalized Patients with Covid-19. The New England journal of medicine. 2021;384(8):693-704. Pub- Med PMID: 32678530. Pubmed Central PMCID: PMC7383595. Epub 2020/07/18. eng.
• 29. Callejas Rubio JL, Luna Del Castillo JD, de la Hera Fernández J, Guirao Arrabal E, Colmenero Ruiz M, Ortego Centeno N. Effectiveness of corticoid pulses in patients with cytokine storm syndrome induced by SARS-CoV-2 infection. Medicina clinica. 2020;155(4):159-61. PubMed PMID: 32532461. Pubmed Central PMCID: PMC7250763 patients. Epub 2020/06/14. eng
• 30. López Zúñiga M, Moreno-Moral A, Ocaña-Granados A, Padilla- Moreno FA, Castillo-Fernández AM, Guillamón-Fernández D, et al. High-dose corticosteroid pulse therapy increases the survival rate in COVID-19 patients at risk of hyper-inflammatory response. PloS one. 2021;16(1):e0243964. PubMed PMID: 33507958. Pubmed Central PMCID: PMC7842890. Epub 2021/01/29. eng.
• 31. Rana MA, Hashmi M, Qayyum A, Pervaiz R, Saleem M, Munir MF, et al. Comparison of Efficacy of Dexamethasone and Methylprednisolone in Improving PaO2/FiO2 Ratio Among COVID- 19 Patients. Cureus. 2020;12(10):e10918. PubMed PMID: 33194485. Pubmed Central PMCID: PMC7657375. Epub 2020/11/17. eng.
• 32. Mareev VY, Orlova YA, Pavlikova EP, Matskeplishvili ST, Krasnova TN, Malahov PS, et al. Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study). Kardiologiia. 2020;60(6):15-29. PubMed PMID: 32720612. Epub 2020/07/29. eng
• 33. 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. PubMed PMID: 34033648. Pubmed Central PMCID: PMC8148307. Epub 2021/05/26. eng.
• 34. Pulakurthi YS, Pederson JM, Saravu K, Gupta N, Balasubramanian P, Kamrowski S, et al. Corticosteroid therapy for COVID- 19: A systematic review and meta-analysis of randomized controlled trials. Medicine. 2021;100(20):e25719. PubMed PMID: 34011029. Pubmed Central PMCID: PMC8137023. Epub 2021/05/21. eng.
• 35. Tavakolpour S, Rakhshandehroo T, Wei EX, Rashidian M. Lymphopenia during the COVID-19 infection: What it shows and what can be learned. Immunology letters. 2020;225:31-2. Pub- Med PMID: 32569607. Pubmed Central PMCID: PMC7305732. Epub 2020/06/23. eng.
• 36. Zidar DA, Al-Kindi SG, Liu Y, Krieger NI, Perzynski AT, Osnard M, et al. Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population. JAMA network open. 2019;2(12):e1916526. PubMed PMID: 31790569. Pubmed Central PMCID: PMC6902755 Epub 2019/12/04. eng.
• 37. Liu J, Li H, Luo M, Liu J, Wu L, Lin X, et al. Lymphopenia predicted illness severity and recovery in patients with COVID-19: A single-center, retrospective study. PloS one. 2020;15(11):e0241659. PubMed PMID: 33206680. Pubmed Central PMCID: PMC7673513. Epub 2020/11/19. eng.