Commercial Immunoglobulin Products Contain Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2023 Oct 05

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Patients with antibody deficiency respond poorly to coronavirus disease 2019 (COVID-19) vaccination and are at risk of severe or prolonged infection. They are given long-term immunoglobulin replacement therapy (IRT) prepared from healthy donor plasma to confer passive immunity against infection. Following widespread COVID-19 vaccination alongside natural exposure, we hypothesized that immunoglobulin preparations will now contain neutralizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies, which confer protection against COVID-19 disease and may help to treat chronic infection. We evaluated anti-SARS-CoV-2 spike antibody in a cohort of patients before and after immunoglobulin infusion. Neutralizing capacity of patient samples and immunoglobulin products was assessed using in vitro pseudovirus and live-virus neutralization assays, the latter investigating multiple batches against current circulating Omicron variants. We describe the clinical course of 9 patients started on IRT during treatment of COVID-19. In 35 individuals with antibody deficiency established on IRT, median anti-spike antibody titer increased from 2123 to 10 600 U/mL postinfusion, with corresponding increase in pseudovirus neutralization titers to levels comparable to healthy donors. Testing immunoglobulin products directly in the live-virus assay confirmed neutralization, including of BQ1.1 and XBB variants, but with variation between immunoglobulin products and batches.Initiation of IRT alongside remdesivir in patients with antibody deficiency and prolonged COVID-19 infection (median 189 days, maximum >900 days with an ancestral viral strain) resulted in clearance of SARS-CoV-2 at a median of 20 days. Immunoglobulin preparations now contain neutralizing anti-SARS-CoV-2 antibodies that are transmitted to patients and help to treat COVID-19 in individuals with failure of humoral immunity. © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Citation

Vinit Upasani, Katie Townsend, Mary Y Wu, Edward J Carr, Agnieszka Hobbs, Giulia Dowgier, Martina Ragno, Lou S Herman, Sonal Sharma, Devesh Shah, Simon F K Lee, Neil Chauhan, Julie M Glanville, Lucy Neave, Steven Hanson, Sriram Ravichandran, Aoife Tynan, Mary O'Sullivan, Fernando Moreira, Sarita Workman, Andrew Symes, Siobhan O Burns, Susan Tadros, Jennifer C L Hart, Rupert C L Beale, Sonia Gandhi, Emma C Wall, Laura McCoy, David M Lowe. Commercial Immunoglobulin Products Contain Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023 Oct 05;77(7):950-960