Efficacy of intravenous immunoglobulin therapy in hospitalised patients with COVID-19: A randomized controlled trial
Abstract
Objectives: Acute respiratory distress syndrome (ARDS) is one of the life-threatening complications of COVID-19. The occurrence of ARDS is due to over activation of the host immune response to the virus. The purpose of this study is to investigate whether administration of intravenous immunoglobulins (IVIG) could enhance the outcomes of sever ill COVID-19 patients with ARDS.
Methods: In this randomized controlled trial in Milad Hospital of Isfahan, Iran, 88 patients randomly were assigned between May to October 2020. The patients had no significant differences in age and sex. The patients divided in two groups: the group who received IVIG and routine treatment (n=44, 50%) and the control group who just treated with routine treatment (n=44, 50%). The outcomes of patients including hospitalization duration, ICU admission period and total death occurrence besides clinical and laboratory parameters were fallowed and compared between two groups.
Results: Primary outcomes of patients including hospitalization duration (P=0.18), ICU admission period (P= 0.35), and mortality (P=0.621) had no significant difference between IVIG group and the control group. At day 3 and day 5 of IVIG administration, clinical and laboratory outcomes had been screened. The clinical parameter that improved was oxygen saturation compared to the control group (87.56 ± 6.72 vs. 86.72 ± 7.52). In cardiovascular system IVIG significantly decreased the diastolic blood pressure (P= 0.02). In terms of coagulation parameters IVIG treatment decreased PTT while it increased D-dimer but no effect on platelet count and PT have been seen. The inflammatory parameters include ESR, CRP, and IL6 had no superior changes between IVIG group and the control group.
Conclusion: Our study demonstrated that there were no superior advantages in COVID-19 patients with ARDS who treated with IVIG.
2. SeyedAlinaghi S, Afsahi AM, MohsseniPour M, Behnezhad F, Salehi MA, Barzegary A, et al. Late complications of COVID-19; a systematic review of current evidence. Archives of academic emergency medicine. 2021;9(1).
3. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LF. The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology. 2020;20(6):363-74.
4. Rokni M, Hamblin MR, Rezaei N. Cytokines and COVID-19: friends or foes? Human vaccines & immunotherapeutics. 2020;16(10):2363-5.
5. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet. 2020;395(10229):1033-4.
6. Del Valle DM, Kim-Schulze S, Huang H-H, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nature medicine. 2020;26(10):1636-43.
7. Group RC. Dexamethasone in hospitalized patients with Covid-19. New England Journal of Medicine. 2021;384(8):693-704.
8. Limen RY, Sedono R, Sugiarto A, Hariyanto TI. Janus kinase (JAK)-inhibitors and coronavirus disease 2019 (Covid-19) outcomes: a systematic review and meta-analysis. Expert Review of Anti-Infective Therapy. 2022;20(3):425-34.
9. Ivan Hariyanto T, Kurniawan A. Tocilizumab administration is associated with the reduction in biomarkers of coronavirus disease 2019 infection. Journal of Medical Virology. 2021;93(3):1832-6.
10. Mazeraud A, Jamme M, Mancusi RL, Latroche C, Megarbane B, Siami S, et al. Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial. The Lancet Respiratory Medicine. 2022;10(2):158-66.
11. Chaigne B, Mouthon L. Mechanisms of action of intravenous immunoglobulin. Transfusion and Apheresis Science. 2017;56(1):45-9.
12. Jolles S, Sewell W, Misbah S. Clinical uses of intravenous immunoglobulin. Clinical & Experimental Immunology. 2005;142(1):1-11.
13. Galeotti C, Kaveri SV, Bayry J. IVIG-mediated effector functions in autoimmune and inflammatory diseases. International immunology. 2017;29(11):491-8.
14. Gharebaghi N, Nejadrahim R, Mousavi SJ, Sadat-Ebrahimi S-R, Hajizadeh R. The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial. BMC infectious diseases. 2020;20:1-8.
15. Xiang H-r, Cheng X, Li Y, Luo W-w, Zhang Q-z, Peng W-x. Efficacy of IVIG (intravenous immunoglobulin) for corona virus disease 2019 (COVID-19): A meta-analysis. International immunopharmacology. 2021;96:107732.
16. Focosi D, Franchini M, Tuccori M, Cruciani M. Efficacy of high-dose polyclonal intravenous immunoglobulin in COVID-19: A systematic review. Vaccines. 2022;10(1):94.
17. Cao W, Liu X, Bai T, Fan H, Hong K, Song H, et al., editors. High-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019. Open forum infectious diseases; 2020: Oxford University Press US.
18. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The lancet. 2020;395(10223):507-13.
19. Jamaati H, Dastan F, Tabarsi P, Marjani M, Saffaei A, Hashemian SM. A fourteen-day experience with coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS): an Iranian treatment protocol. Iranian Journal of Pharmaceutical Research: IJPR. 2020;19(1):31.
20. Chaigne B, Mouthon L. Mechanisms of action of intravenous immunoglobulin. Transfus Apher Sci. 2017;56(1):45-9.
21. Shoenfeld Y. Corona (COVID-19) time musings: Our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning. Autoimmun Rev. 2020;19(6):102538.
22. Shao Z, Feng Y, Zhong L, Xie Q, Lei M, Liu Z, et al. Clinical efficacy of intravenous immunoglobulin therapy in critical ill patients with COVID-19: a multicenter retrospective cohort study. Clin Transl Immunology. 2020;9(10):e1192.
23. Mazeraud A, Jamme M, Mancusi RL, Latroche C, Megarbane B, Siami S, et al. Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022;10(2):158-66.
24. Raman RS, Bhagwan Barge V, Anil Kumar D, Dandu H, Rakesh Kartha R, Bafna V, et al. A Phase II Safety and Efficacy Study on Prognosis of Moderate Pneumonia in Coronavirus Disease 2019 Patients With Regular Intravenous Immunoglobulin Therapy. J Infect Dis. 2021;223(9):1538-43.
25. Kow CS, Hasan SS. Glucocorticoid versus immunoglobulin in the treatment of COVID-19-associated fulminant myocarditis. Infection. 2020;48(5):805-6.
26. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 2020;5(7):802-10.
27. Wu C, Hu X, Song J, Du C, Xu J, Yang D, et al. Heart injury signs are associated with higher and earlier mortality in coronavirus disease 2019 (COVID-19). MedRxiv. 2020:2020.02. 26.20028589.
28. Liu J, Chen Y, Li R, Wu Z, Xu Q, Li Z, et al. Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study. Clin Microbiol Infect. 2021;27(10):1488-93.
29. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm' in COVID-19. J Infect. 2020;80(6):607-13.
30. Chien JY, Hsueh PR, Cheng WC, Yu CJ, Yang PC. Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome. Respirology. 2006;11(6):715-22.
31. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2.
32. Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020;39(7):2085-94.
Files | ||
Issue | Vol 2 No 2 (2024): . | |
Section | Original Articles | |
DOI | https://doi.org/10.18502/abi.v2i2.17935 | |
Keywords | ||
IVIG COVID-19 coronavirus ARDS |
Rights and permissions | |
![]() |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |