Functional Antibodies in COVID-19 Convalescent Plasma

Area of Science:

• Immunology
• Virology
• Therapeutics

Background:

• Convalescent plasma (CCP) was an early therapeutic strategy for SARS-CoV-2 infection when vaccines and specific treatments were unavailable.
• CCP trials yielded mixed results, complicated by its nature as a heterogeneous product derived from individual recovered patients.
• The therapeutic benefit of antibodies in CCP may extend beyond neutralization, involving interactions with the innate immune system.

Approach:

• Deeply profiled SARS-CoV-2-specific Fc-responses in CCP donors and recipients.
• Analyzed pre- and post-transfer humoral profiles.
• Investigated antibody functions, including antiviral and anti-inflammatory effects.

Key Points:

• Significant SARS-CoV-2 specific Fc-heterogeneity observed in CCP units and recipients.
• CCP units contained more functional antibodies than acute COVID-19 patients.
• Antibody immunomodulatory effects varied based on patient's pre-existing Spike (S)-specific IgG titers.

Conclusions:

• CCP's therapeutic benefit is influenced by diverse antibody functions, including Fc-mediated effects, not just neutralization.
• Both Spike (S) and Nucleocapsid (N) specific antibodies contribute to antiviral and anti-inflammatory actions.
• Findings provide a basis for interpreting immunity correlates in CCP trials and designing next-generation therapeutics.