Detection of SARS-CoV-2 Antibodies in Immunoglobulin Products

The objective of this study was to quantitively evaluate SARS-CoV-2 antibody levels in currently availably immunoglobulin products.This study examined 142 unique lots of 11 different immunoglobulin products (both intravenous [IV] and subcutaneous formulations).The immunoglobulin lots were assessed for Ig-binding activities against severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) receptor binding domain, spike, and nucleocapsid proteins by ELISA assays. Additionally, functionality of 48 lots were assessed for their ability to inhibit several SARS-CoV-2 variants spike binding to angiotensin-converting enzyme 2 (ACE2).Of the 11 immunoglobulin products evaluated, 8 of them (72%) contained detectable anti-SARS-CoV-2 antibodies. Immunoglobulin products manufactured after the year 2020 (with expiration dates 2023–2024) had significantly higher antibody levels compared with products manufactured prepandemic (before 2020). Sixty percent of the products with expiration dates of 2023 and 85% of the products with expiration dates of 2024 contained antibodies to SARS-CoV-2 proteins. Immunoglobulin products with later dates of expiration were strongly associated with inhibition of ACE2-binding activity. The 10% products used for IV administration had greater inhibition of ACE2-binding activity than the 20% products used for SC administration.Immunoglobulin products with later expiration dates (2023–2025) had significantly higher antibody levels, binding, and inhibition activities against SARS-CoV-2 proteins when compared with prepandemic lots. These more recent immunoglobulin products may be therapeutically beneficial to patients who do not have a robust SARS-CoV-2 vaccine response.This is a large study of 11 different immunoglobulin products commonly used in patients with predominantly antibody deficiency. The more recent immunoglobulin products (expiration dates 2023–2025) not only contained detectable higher anti-SARS-CoV-2 antibody levels but also had higher binding and inhibition activities against SARS-CoV-2 proteins when compared with prepandemic product. Interestingly, the 10% IV immunoglobulin products had greater inhibition of ACE2-binding activity than the 20% SC immunoglobulins, which clinicians may want to consider when starting immunoglobulin replacement therapy in a patient with recurrent COVID-19 infection or poor vaccine response. This study was limited by a lack of consistency in number of lots of each product evaluated. Clinicians need to be aware that the more recent immunoglobulin products (expiration dates 2023–2025) may offer greater therapeutic effect and be especially beneficial to patients who lack adequate SARS-CoV-2 vaccine response.