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.
Interestingly, investigations probing the efficacy of IVIG in treating PASC have demonstrated conflicting results. Some studies have reported that IVIG may be efficacious in treating conditions associated with PASC (Boehm and Packer, 2022), while others have found no significant effect (Sakoulas et al., 2020, Tabarsi et al., 2021, Xiang et al., 2021). Research is ongoing to demonstrate the efficacy of IVIG in treating these conditions and further studies will be necessary to fully understand its mechanisms of action and optimal dosing regimen.
Access to IVIG is often hindered by insurance coverage limitations and high treatment costs. Insurance criteria and restrictions can make it difficult for patients to obtain coverage for IVIG, often requiring pre-authorization forms or extensive documentation to approve IVIG administration. Meanwhile, the high cost of the treatment puts it out of reach for those who are refused full coverage.
The biological mechanism underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), is not entirely clear. However, the link between ME/CFS and other autoimmune conditions is well established. Further, prior work suggests that, in some patients, there may be an autoimmune etiology for this condition, as in PASC (Sotzny et al., 2018).
Multiple studies have demonstrated a rise in various B-cell phenotypes associated with ME. Tirelli et al. first reported increases in the number of CD19 + cells (Tirelli et al., 1994). In 2013, Bradley et al. demonstrated heightened numbers of naive and transitional B-cells (Bradley et al., 2013). Notably, elevated numbers in CD24 + cells, which are seen in other autoimmune conditions such as MS, rheumatoid arthritis, and systemic lupus erythematosus, have also been reported in ME/CFS (Mensah et al., 2016). The same study also found increased IgG levels in patients’ CSF. Finally, autoantibodies have been reported in patients with ME, including one study that found that 52 % of patients (n = 60) had antinuclear antibodies. (Konstantinov et al., 1996).
In 2015, a phase II clinical trial demonstrated that B-cell depletion is efficacious in treating ME/CFS in over 50 % of patients (Fluge et al., 2015). Interestingly, IVIG was capable of depressing B-cell levels, with one study finding that IVIG can suppress B-cells in MS patients and another demonstrating that IVIG can induce selective B-cell depletion in patients with common variable immunodeficiency
There is a wide spectrum of immunological disturbances associated with acute COVID-19.
As IVIG can replenish IgG, inhibit the complement system, and prevent the formation of membrane attack complexes, as well as neutralize inflammatory cytokines and dampen macrophage and microglial activation (see Fig. 1), its use has been welcomed as an acute therapy in COVID-19, although trial results continue to be debated
both ME/CFS and PASC share a potentially “autoimmune nature” that is not well characterized.
