Efficacy of intravenous immunoglobulins (IVIG) in COVID-19 patients: a systematic review and meta-analysis

Behzad Fatemi , Soheila Rezaei, Mohammad Peikanpour , Farzaneh Dastan, Ali Saffaei

Abstract


Background and purpose: Though controversial, many clinical trials have been conducted to evaluate the efficacy of intravenous immunoglobulins (IVIG) in COVID-19 cases. Therefore, a systematic review and meta-analysis have been performed to evaluate the efficacy of IVIG in the treatment of COVID-19 patients. Experimental approach: A systematic search was performed in electronic databases and preprint servers up to November 20, 2021. Since substantial heterogeneity was expected, a random-effects model was applied to pool effect size from included studies to calculate the standardized mean differences (SMDs) for the continuous variables and relative risks (RRs) for the dichotomous variable with 95% confidence intervals (CIs). Findings/Results: Five randomized clinical trials and seven cohort studies were analyzed among the 12 eligible studies with a total of 2,156 patients. The pooled RR of mortality was 0.77 (CI 0.59-1.01, P-value = 0.06), and of mechanical ventilation was 1.50 (CI 0.29-7.83; P-value = 0.63) in the IVIG group compared with the standard care group. The pooled SMD of hospital length of stay was 0.84 (CI -0.43-2.11 P-value = 0.20) and of ICU length of stay was -0.07 (CI -0.92-0.78; P-value = 0.86) in the IVIG group compared with the standard care group. Conclusion and implications: This meta-analysis found that the IVIG therapy was not statistically different from the standard care group. Mortality, ICU admission, mechanical ventilation, length of hospital stay, and length of ICU stay were not significantly improved among IVIG recipients. However, statistical indifference is not equal to clinical indifference.


Keywords


Clinical efficacy; Intravenous immunoglobulin; Meta-analysis; Mortality rate; SARS-CoV-2 infection; Systematic review.

Full Text:

PDF

References


WHO. Coronavirus disease (COVID-19): weekly epidemiological update. World Health Organization. 2020:1-22. Available from:

https://apps.who.int/iris/bitstream/handle/10665/334169/nCoV-weekly-sitrep30Aug20-eng.pdf

Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun.2020;109:102433,1-5.DOI: 10.1016/j.jaut.2020.102433.

Rastin M, Mahmoudi M, Sahebari M, Tabasi N. Clinical & immunological characteristics in systemic lupus erythematosus patients. Indian J Med Res. 2017;146(2):224-229. DOI: 10.4103/ijmr.IJMR_1356_15.

Rezaei S, Fatemi B, Karimi Majd Z, Minaei H, Peikanpour M, Anjidani N, et al. Efficacy and safety of Tocilizumab in severe and critical COVID-19: a systematic review and meta-analysis. Expert Rev Clin Immunol. 2021;17(5):499-511.DOI: 10.1080/1744666X.2021.1908128.

Ataee MH, Mirhosseini SA, Mirnejad R, Rezaie E, Mahmoodzadeh Hosseini H, et al. Design of two immunotoxins based rovalpituzumab antibody against DLL3 receptor; a promising potential opportunity. Res Pharm Sci. 2022;17(4):428-444. DOI: 10.4103/1735-5362.350243.

Yazdani M, Khezri J, Hadizadeh N, Zamani J, Zakaria A, Naderi M, Mahmoodian S, et al. Depinar, a drug that potentially inhibits the binding and entry of COVID-19 into host cells based on computer-aided studies. Res Pharm Sci. 2021;16(3):315-325. DOI: 10.4103/1735-5362.314830.

Tabarsi P, Barati S, Jamaati H, Haseli S, Marjani M, Moniri A, Abtahian Z, et al. Evaluating the effects of intravenous immunoglobulin (IVIg) on the management of severe COVID-19 cases: a randomized controlled trial. Int Immunopharmacol. 2021;90:107205.DOI: 10.1016/j.intimp.2020.107205.

Dalakas MC. Mechanisms of action of IVIg and therapeutic considerations in the treatment of acute and chronic demyelinating neuropathies. Neurology. 2002;59(12 Suppl 6):S13-S21.DOI: 10.1212/wnl.59.12_suppl_6.s13.

Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;5:520,1-17.DOI: 10.3389/fimmu.2014.00520.

Moradimajd P, Samaee H, Sedigh-Maroufi S, Kourosh-Aami M, Mohsenzadagan M. Administration of intravenous immunoglobulin in the treatment of COVID-19: a review of available evidence. J Med Virol. 2021;93(5):2675-2682.DOI: 10.1002/jmv.26727.

Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA. 2020;323(13):1239-1242. DOI: 10.1001/jama.2020.2648.

Varghese GM, John R, Manesh A, Karthik R, Abraham OC. Clinical management of COVID-19. Indian J Med Res. 2020;151(5):401-410.

Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-1558.DOI: 10.1002/sim.1186.

Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane handbook for systematic reviews of intervention. Vol. 2, Chichester (UK): John Wiley & Sons; 2011.p. 649. Available from: https://training.cochrane.org/handbook.

Dersimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-188.DOI: 10.1016/0197-2456(86)90046-2.

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):1538-1543.DOI: 10.1093/infdis/jiab098.

Gharebaghi N, Nejadrahim R, Mousavi SJ, Sadat-Ebrahimi SR, 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 Infect Dis. 2020;20(1):786,1-8.DOI: 10.1186/s12879-020-05507-4.

Gonzalez JLB, González Gámez M, Mendoza Enciso EA, Esparza Maldonado RJ, Palacios DH, Campos SD, et al. Efficacy and safety of convalescent plasma and intravenous immunoglobulin in critically ill COVID-19 patients. A controlled clinical trial. medRxiv. 2021;2021:1-23. DOI: 10.1101/2021.03.28.21254507.

Tabarsi P, Barati S, Jamaati H, Haseli S, Marjani M, Moniri A, et al. Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial. Int Immunopharmacol. 2021;90:107205,1-6.DOI: 10.1016/j.intimp.2020.107205.

Sakoulas G, Geriak M, Kullar R, Greenwood KL, Habib M, Vyas A, et al. Intravenous immunoglobulin plus methylprednisolone mitigate respiratory morbidity in Coronavirus disease 2019. Crit Care Explor. 2020;2(11):e0280,1-7.DOI: 10.1097/CCE.0000000000000280.

Esen F, Özcan PE, Orhun G, Polat Ö, Anaklı İ, Alay G, et al. Effects of adjunct treatment with intravenous immunoglobulins on the course of severe COVID-19: results from a retrospective cohort study. Curr Med Res Opin. 2021;37(4):543-548. DOI: 10.1080/03007995.2020.1856058.

Cao W, Liu X, Hong K, Ma Z, Zhang Y, Lin L, et al. High-dose intravenous immunoglobulin in severe coronavirus disease 2019: A multicenter retrospective study in China. Front Immunol. 2021;12:627844,1-12.DOI: 10.3389/fimmu.2021.627844.

Farrokhpour M, Rezaie N, Moradi N, Ghaffari Rad F, Izadi SS, Azimi M, et al. Infliximab and intravenous gammaglobulin in hospitalized severe COVID-19 patients in intensive care unit. Arch Iran Med. 2021;24(2):139-143. DOI: 10.34172/aim.2021.22.

Huang C, Fei L, Li W, Xu W, Xie X, Li Q, et al. Efficacy evaluation of intravenous immunoglobulin in non-severe patients with COVID-19: a retrospective cohort study based on propensity score matching. Int J Infect Dis. 2021;105:525-531. DOI: 10.1016/j.ijid.2021.01.009.

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 Immunol. 2020;9(10):e1192,1-10.DOI: 10.1002/cti2.1192. eCollection 2020.

Hou X, Tian L, Zhou L, Jia X, Kong L, Xue Y, et al. Intravenous immunoglobulin-based adjuvant therapy for severe COVID-19: a single-center retrospective cohort study. Virol J. 2021;18(1):101,1-7. DOI: 10.1186/s12985-021-01575-3.

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):1488-1493. DOI: 10.1016/j.cmi.2021.05.012

Xiang HR, Cheng X, Li Y, Luo WW, Zhang QZ, Peng WX. Efficacy of IVIG (intravenous immunoglobulin) for coronavirus disease 2019 (COVID-19): A meta-analysis. Int Immunopharmacol. 2021;96:107732,1-9. DOI: 10.1016/j.intimp.2021.107732.

Kolahchi Z, Sohrabi H, Ekrami Nasab S, Jelodari Mamaghani H, Keyfari Alamdari M, Rezaei N. Potential therapeutic approach of intravenous immunoglobulin against COVID-19. Allergy, Asthma Clin Immunol. 2021;17(1):105-116. DOI: 10.1186/s13223-021-00609-3.

Guo Y, Tian X, Wang X, Xiao Z. Adverse effects of immunoglobulin therapy. Front Immunol. 2018;9:1299,1-13.DOI: 10.3389/fimmu.2018.01299. eCollection 2018.

Moitra VK, Guerra C, Linde-Zwirble WT, Wunsch H. Relationship between ICU length of stay and long-term mortality for elderly ICU survivors. Crit Care Med. 2016;44(4):655-662. DOI: 10.1097/CCM.0000000000001480.

Sharma A, Tiwari S, Deb MK, Marty JL. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): a global pandemic and treatment strategies. Int J Antimicrob Agents. 2020;56(2):106054,1-14. DOI: 10.1016/j.ijantimicag.2020.106054.

Pei L, Zhang S, Huang L, Geng X, Ma L, Jiang W, et al. Antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin in 1142 patients with coronavirus disease. 2019: a systematic review and meta-analysis. Pol Arch Intern Med.2020; 130(9):726-733DOI: 10.20452/pamw.15543


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.