Review A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and [LC]... 2024 Melamed et al

Full title: A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome

Highlights

• IVIG has demonstrated efficacy in over 100 disorders, spanning hematologic, inflammatory, autoimmune, and infectious diseases.
• The mechanisms of action for IVIG include: neutralization of inflammatory cytokines and autoantibodies, saturation of FcRNs, complement inhibition, and regulation of the innate and adaptive immune systems.
• Recent trials studying IVIG as a treatment for acute COVID-19 have produced mixed results.
• IVIG is being explored as a potential treatment for PASC, with initial small cohort studies reporting beneficial results and clinical trials currently underway in larger cohorts.
• Future studies on IVIG efficacy in PASC could focus on creating homogenous patient subgroups based on specific symptom clusters, dosing, and timing of IVIG administration

Abstract

Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy that has been studied in several neuroimmune conditions, such as Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and multiple sclerosis. It has also been proposed as a potential treatment option for acute COVID-19 infection and post-acute sequelae of SARS-CoV-2 infection (PASC). IVIG is thought to function by providing the recipient with a pool of antibodies, which can, in turn, modulate immune responses through multiple mechanisms including neutralization of cytokines and autoantibodies, saturation of neonatal fragment crystallizable receptors, inhibition of complement activation, and regulation of T and B cell mediated inflammation.

In acute COVID-19, studies have shown that early administration of IVIG and plasmapheresis in severe cases can reduce the need for mechanical ventilation, shorten ICU and hospital stays, and lower mortality. Similarly, in PASC, while research is still in early stages, IVIG has been shown to alleviate persistent symptoms in small patient cohorts. Furthermore, IVIG has shown benefits in another condition which has symptomatic overlap with PASC, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), though studies have yielded mixed results. It is important to note that IVIG can be associated with several potential adverse effects, such as anaphylaxis, headaches, thrombosis, liver enzyme elevations and renal complications. In addition, the high cost of IVIG can be a deterrent for payers and patients.

This review provides a comprehensive update on the use of IVIG in multiple neuroimmune conditions, ME/CFS, acute COVID-19, and PASC, as well as covers its history, production, pricing, and mechanisms of action. We also identify key areas of future research, including the need to optimize the use of Ig product dosing, timing, and patient selection across conditions, particularly in the context of COVID-19 and PASC.

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