21. Impact of Plasma Collection Date on Antibodies to SARS-CoV-2 in Intravenous Immunoglobulin

Background: Intravenous immunoglobulin (IVIG) products contain a broad spectrum of antibodies and provide protection for patients with primary immunodeficiency (PI) against common infections. The antibody profile reflects that of the plasma donor population and donor exposure to viruses such as SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Plasma donors’ antibody levels against SARS-CoV-2 tend to decrease over time. This decline starts with the first donation (at least two weeks after recovery, following FDA guidelines) and continues up to at least 8 weeks after exposure.

Purpose: This study was initiated to assess the impact of plasma collection during and after the COVID-19 pandemic on antibody levels in two IVIG products and provide information on the criticality of plasma collection during a pandemic.

Methods: Gammaplex 5% (50 g/L) and 10% (100 g/L) are IVIG solutions licensed for the treatment of PI. Screening was performed on a total of 82 batches: 21 batches filled in 2021, 35 batches filled in 2022, and 26 batches filled in 2023. Of the 82 batches tested, 77 were IVIG 10% and 5 were IVIG 5%. Tests were carried out on the finished product using a neutralizing antibody detection assay (GenScript c-Pass kit) which measures the antibodies in a sample able to bind to the SARS-CoV-2 spike protein and prevent it binding to immobilized host-cell ACE-2 receptors. Results are reported with reference to the WHO International Standard for antibodies to SARS-CoV-2.

Results: The results show detectable levels of antibodies to SARS-CoV-2 in batches of these two IVIG products tested across all three years. Levels of antibodies are shown to increase significantly from 2021 to 2022 (p < 0.01) but no significant difference was observed between levels in 2022 and 2023 (p 0.53). Neutralizing antibody potency of the tested IVIG batches ranged from 0 to 644 IU/mg IgG with a mean potency of 215 IU/mg IgG and a median potency of 213 IU/mg IgG. The potency distribution of batches is also shown to change with non-normal distribution in 2021 and 2022 but a normal distribution in 2023, suggesting antibody levels in these two products have stabilized in this period.

Discussion: This longitudinal review of SARS-CoV-2 antibody levels shows that these two IVIG products continue to provide antibodies against COVID in the post-pandemic period. The results show a good correlation between the proportion of plasma donations collected following widespread exposure to SARS-CoV-2 in the USA and the antibody levels in intravenous immunoglobulin finished products (p 0.64). The slight reduction in levels in 2023 compared with the peak in 2022 may indicate a stabilization of antibody levels associated with immunization amongst plasma donors.

Conclusions: The timing of the pandemic and the detection of widespread stable antibody levels in intravenous immunoglobulin products has implications for future pandemics and for the level of protection afforded to immune deficient patients. Ensuring measures are in place to allow safe plasma collection and processing from the start of a pandemic allows IVIG batches containing protective antibodies to be made available to immune deficient patients as soon as possible.