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Intravenous Immunoglobulin Effective in Achieving Viral Clearance, Neutralizing Several SARS-CoV-2 Variants
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In an analysis of 16 immunocompromised patients with COVID-19, intravenous immunoglobulin was effective and associated with clinical cure.
Intravenous immunoglobulin (IVIG) antibodies were found to efficiently neutralize several variants of SARS-CoV-2, the virus that causes COVID-19, and were associated with viral clearance and clinical cure in immunocompromised patients, according to results from a study published in the International Journal of Infectious Diseases.1
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Oftentimes, patients with severe immunodeficiencies exhibit a poor response to COVID-19 vaccines, in addition to being saddled with a higher risk of severe and/or persistent disease.1
An unexplored treatment alternative is commercially available post-pandemic IVIG, which have been shown to contain large levels of SARS-CoV-2 neutralizing immunoglobulin G (IgG). However, studies using IVIG towards COVID-19 in patients who are immunocompromised are lacking.1
In this retrospective cohort study, the investigators assessed the clinical and virological outcomes associated with IVIG in immunocompromised, vaccine non-responding adults. The primary outcome was clinical cure, which is defined as survival and resolution as COVID-19 symptoms.1
A total of 16 patients were included in the study. Patients received daily doses of 20 g of IVIG, for a total median dose of 60 g (range 20-80 g). After 2 days, all 15 surviving patients exhibited defervescence and an improved general condition. In addition, demand for supplemental oxygen declined, and after a median of 3 days oxygen could be withdrawn.1
At the follow-up point, viral clearance—the presence of no detectable viral RNA in the nasopharynx or plasma—occurred in 13 participants. Two patients experienced a relapse of COVID-19 with viremia over 100 days after baseline; after additional IVIG was administered, there was a rapid clearance of symptoms.1
In a previous study, covered in Pharmacy Times, IVIG was found to have an insignificant benefit towards the length of hospitalization or reducing mortality in patients with COVID-19. Across 13 studies, 2313 patient outcomes were evaluated. In 7 of them, there was not a statistical benefit to mortality found.2
However, there was a significant effect in the group of patients with severe COVID-19 that were critically ill, as they favored IVIG treatment. A meta-analysis reflected a similar lack of efficacy surrounding mortality, but it had a statistically significant association with the length of hospital stay for patients in the moderate severity group.2
These findings reflect those of the current study, which associate IVIG with several clinical benefits in the cohort. Importantly, IVIG appeared safe and without severe adverse effects, and most of the patients were sufficiently treated without the use of other antivirals.1,2
The study authors, Gröning et al.,reference Upasani et al.’s work on demonstrating the presence of neutralizing antibodies against SARS-CoV-2 spike protein in patient serum. They note, however, that “there is considerable variety between products and potentially between batches” of IVIG.3
Gröning et al. indicated a similar transfer of neutralizing anti-SARS-CoV-2 antibodies after treatment with IVIG. These antibody levels were observed to wane over time, and relapse of COVID-19 can occur in some cases, which warrants follow-up IVIG sampling.1,3
Neutralizing capacity was universally high against only the 2019-nCoV and BA.2 variants, although IgG binding levels were generally high across all tested variants. IgG binding levels increased across all tested variants after IVIG infusion.1
The investigators noted that lower doses could be sufficient for treating COVID-19, and that different dose levels could be addressed in future studies. Furthermore, they discussed that the timing of IVIG treatment may also be important, and that early IVIG treatment could be beneficial to improving outcomes.1
“Our data suggests that IVIG could be a novel treatment alternative for COVID-19 for this patient category,” the investigators concluded.1
References
1. Gröning R, Walde J, Ahlm C, et al. Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients: a retrospective cohort study. Intl Journ Infect Diseases. 2024;144:107046. doi:10.1016/j.ijid.2024.107046
2. McGovern G. IVIG therapy shows insignificant benefit to reducing mortality, length of hospitalization in patients with COVID-19. Pharmacy Times. Published September 19, 2023. Accessed August 1, 2024.
3. Upasani V, O’Sullivan M, Moreira F, et al. Commercial immunoglobulin products now contain neutralizing antibodies against SARS-CoV-2 spike protein which are detectable in patient serum. 2022. medRxiv. doi:10.1101/2022.09.22.22280216
