Intravenous Immunoglobulin Does Not Improve Clinical Outcomes Compared With Tocilizumab in Severe COVID-19

Patients with severe COVID-19, the virus caused by infection with SARS-CoV-2, in the early phase of their disease did not present improved clinical outcomes regarding intensive care unit admission, hospitalization time, and mortality when treated with intravenous immunoglobulin (IVIG) compared with those who received tocilizumab (Actemra; Genentech), according to the results of a retrospective study published by investigators in the Journal of Sao Paulo Institute of Tropical Medicine.¹

Intravenous immunoglobulin administration helps a patient develop an anti-inflammatory response to viral threats. | Image Credit: © sakurra - stock.adobe.com

IVIG Could Play Role in Treating Severe COVID-19

Though COVID-19 infections are typically mild in nature or asymptomatic, severe respiratory issues that necessitate hospitalization are possible. Severe COVID-19 is thought to be induced by an abnormal and excessive inflammatory response, for which anti-inflammatory treatments such as IVIG or Janus kinase (JAK) inhibitors like tocilizumab can be effective.^1,2

IVIG, with its immunomodulatory effects, can help achieve viral clearance and neutralize several variants of SARS-CoV-2 in immunocompromised patients with severe disease, according to various authors. However, other previously published literature is contradictory. One meta-analysis from 2022 indicated that IVIG did not have a positive effect on mortality in patients with moderate COVID-19, though it did have a meaningful effect on shortening hospital stays. On another note, a meta-analysis that specifically focused on critical COVID-19 illness—comprising patients requiring higher oxygen supplementation—did not find any clinical benefit.^3-5

The authors of the current study recognized the gap in research regarding the effectiveness of IVIG in patients with severe, but not critical, COVID-19 infection, which are patients requiring low levels of oxygen support. Further, no studies are present in the literature that compare IVIG with tocilizumab, which is an anti-inflammatory treatment proven to be effective in COVID-19 and approved by the FDA for this indication in patients requiring oxygen. Therefore, they designed a retrospective analysis to evaluate the impact of early treatment with tocilizumab and IVIG on the clinical course of patients with severe COVID-19 pneumonia.^1,6

Comparison with Tocilizumab Shows Insignificant Differences, More Adverse Events With IVIG

Across the follow-up period, 74 patients diagnosed with COVID-19 undergoing IVIG and/or tocilizumab treatment were identified, with 29 (39%) patients receiving IVIG alone, 26 (35%) receiving tocilizumab alone, and 19 (26%) receiving both tocilizumab and IVIG. In an early indicator of insignificant effects, there was a significantly higher rate of ICU admissions in patients receiving both treatments than in the other 2 groups and similar rates in patients receiving either IVIG or tocilizumab alone. There was no statistically significant difference in mortality in patients receiving IVIG alone compared with those receiving tocilizumab alone, according to the investigators.¹

Regarding adverse events (AEs), in 2 patients, IVIG treatment had to end due to the development of bradycardia during infusions. Furthermore, 2 patients developed symptoms that were deemed compatible with transfusion-associated circulatory overload-acute pulmonary edema—within the first 6 hours upon completing IVIG. Notably, there were no serious drug-related AEs observed during or following tocilizumab administration.¹

In their discussion, the authors explained how IVIG can provide numerous benefits, including limiting hyperinflammation, providing anti-infective properties, and reducing mortality and morbidity in difficult-to-treat diseases. Additionally, they discuss how the timing of IVIG administration may be critical compared with other anti-inflammatory treatments. Administering IVIG prior to the severe disease stage could be more effective at inducing antiviral effects of treatment, though the financial barriers to such a strategy are cumbersome, according to the study authors.¹

“There are no data to support the use of IVIG in COVID-19 treatment due to the higher incidence of serious side effects in IVIG recipients and the significantly higher cost of IVIG treatment compared to tocilizumab,” the study investigators concluded.¹

REFERENCES

1. Ali Tuz M, Turkoz I, Aydogan O, et al. Tocilizumab and IVIG experience during the service follow-up in patients with severe COVID-19 pneumonia.

2. Bhimraj A, Morgan RL, Shumaker AH, Baden LR, Cheng VC, Edwards KM, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 (September 2022) Clin Infect Dis. 2024;78:e250–e349. doi: 10.1093/cid/ciac724

3. Halpern L. Intravenous immunoglobulin effective in achieving viral clearance, neutralizing several SARS-CoV-2 variants. Pharmacy Times. Published August 2, 2024. Accessed April 23, 2025. https://www.pharmacytimes.com/view/intravenous-immunoglobulin-effective-in-achieving-viral-clearance-neutralizing-several-sars-cov-2-variants

4. Focosi D, Franchini M, Tuccori M, Cruciani M, et al. Efficacy of high-dose polyclonal intravenous immunoglobulin in COVID-19: A systematic review. Vaccines. 2022;10(1):94. doi:10.3390/vaccines10010094

5. Marcec R, Dodig VM, Radanovic I, Likic R. Intravenous immunoglobulin (IVIG) therapy in hospitalized adult COVID-19 patients: A systematic review and meta-analysis. Reviews in Med Virology. 2022;32(6):e2397. doi:10.1002/rmv.2397

6. Gallagher A. FDA approves tocilizumab as first monoclonal antibody treatment of COVID-19. Pharmacy Times. Published December 22, 2022. Accessed April 23, 2025. https://www.pharmacytimes.com/view/fda-approves-tocilizumab-as-first-monoclonal-antibody-treatment-of-covid-19