Neutralizing SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Give Patients with X-Linked Agammaglobulinemia Limited Passive Immunity to the Omicron Variant

Abstract

Immunodeficient individuals often rely on donor-derived immunoglobulin (Ig) replacement therapy (IGRT) to prevent infections. The passive immunity obtained by IGRT is limited and reflects the state of immunity in the plasma donor population at the time of donation. The objective of the current study was to describe how the potential of passive immunity to SARS-CoV-2 in commercial off-the-shelf Ig products used for IGRT has evolved during the pandemic. Samples were collected from all consecutive Ig batches (n = 60) from three Ig producers used at the Immunodeficiency Unit at Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until January 2022. SARS-CoV-2 antibody concentrations and neutralizing capacity were assessed in all samples. In vivo relevance was assessed by sampling patients with XLA (n = 4), lacking endogenous immunoglobulin synthesis and on continuous Ig substitution, for plasma SARS-CoV-2 antibody concentration. SARS-CoV-2 antibody concentrations in commercial Ig products increased over time but remained inconsistently present. Moreover, Ig batches with high neutralizing capacity towards the Wuhan-strain of SARS-CoV-2 had 32-fold lower activity against the Omicron variant. Despite increasing SARS-CoV-2 antibody concentrations in commercial Ig products, four XLA patients on IGRT had relatively low plasma concentrations of SARS-CoV-2 antibodies with no potential to neutralize the Omicron variant in vitro. In line with this observation, three out the four XLA patients had symptomatic COVID-19 during the Omicron wave. In conclusion, 2 years into the pandemic the amounts of antibodies to SARS-CoV-2 vary considerably among commercial Ig batches obtained from three commercial producers. Importantly, in batches with high concentrations of antibodies directed against the original virus strain, protective passive immunity to the Omicron variant appears to be insufficient.

A Case of Autoimmune Small Fiber Neuropathy as Possible Post COVID Sequelae

“…One major limitation of our case report is the administration of the intravenous immunoglobulin preparation five days before anti-SARS-CoV-2 antibody measurement. There is increasing evidence that anti-SARS-CoV-2 antibodies are present in currently available immunoglobulin products [ 69 , 70 , 71 ]. Therefore, an anti-SARS-CoV-2 antibody measurement might be biased in the reported patient.…”

Monoclonal Antibodies for COVID-19 in X-linked Agammaglobulinemia: a Case Series

“…Nonetheless, despite very heterogenous presentations, all five patients had favorable outcomes with anti-SARS-CoV-2 mAbs, suggesting its efficacy in patients with profound antibody deficiencies like XLA. Hence, monoclonal antibodies may be considered in the treatment of XLA patients, especially in the setting of severe or persistent disease since their antibody response to mRNA COVID-19 vaccination is absent [ 3 ] and neutralizing SARS-CoV-2 antibodies in commercial immunoglobulin products give insufficient passive immunity to the Omicron variant of concern (VOC) [ 4 ]. Other treatments, such as antiviral therapies, have been reported in the treatment of XLA patients with COVID-19 with successful outcomes and could also be considered for these patients.…”

Immune response to COVID-19 vaccines in people with immunodeficiencies

“…26 Despite this, IgRT recipients did not display higher anti-S IgG antibody concentrations than non-IgRT recipients at any timepoint, supporting evidence that IgRT provides limited passive immunity. 27 While self-reported treatment was a limitation in our study, use of IgRT and other immunomodulators did not appear to greatly alter our conclusions.…”